CN102048694B - Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof - Google Patents
Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof Download PDFInfo
- Publication number
- CN102048694B CN102048694B CN2009101984505A CN200910198450A CN102048694B CN 102048694 B CN102048694 B CN 102048694B CN 2009101984505 A CN2009101984505 A CN 2009101984505A CN 200910198450 A CN200910198450 A CN 200910198450A CN 102048694 B CN102048694 B CN 102048694B
- Authority
- CN
- China
- Prior art keywords
- solution
- polyethylene glycol
- liver tumor
- polypeptide
- pamam
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention belongs to the field of biotechnology, relates to a medicine delivery system, in particular to a novel polypeptide-modified liver tumor-targeted nano medicine delivery system and a preparation method thereof. In order to overcome the defects of the conventional liver tumor-targeted medicine delivery system, novel polypeptide is used as a targeted head group, and a cationic polymer material is used as a basic polymer carrier to carry an anti-tumor medicine so as to prepare the liver tumor-targeted nano medicine delivery system. The novel polypeptide screened by the phage display technology is selected to modify the polymer material, the medicine enters cells in an endocytosis mode, the intake of the medicine by the tumor cells is improved, and the safety is ensured. The novel polypeptide-modified liver tumor-targeted nano medicine delivery system has the advantage of taking transferrin as the targeted head group, effectively avoids the interference of endogenous transferrin, has high target and treatment efficiency, is easy and quick to prepare, and can be widely applied to targeted therapies of other tumor tissues.
Description
Technical field
The invention belongs to biological technical field, relate to drug delivery system, be specifically related to liver tumor-targeted nano medicine delivery of a kind of novel polypeptide modification and preparation method thereof.
Background technology
The research that antitumor drug is sent is noticeable focus in recent years, and antitumor drug is different from common small-molecule drug, and its toxic and side effects is large, owing to lack targeting, often the body normal organ is caused very large infringement.Make up Tumor Targeting Drug Delivery System, effectively antitumor drug is transported to tumor locus single-mindedly, the curative effect of performance antitumor drug reduces the whole body toxic and side effects simultaneously, reduces the economic loss that causes thus, is the bottleneck of present oncotherapy.
Liver tumor is that China occupies second cancer, and sickness rate is than the high 2-3 of western countries times, and the characteristics that its grade of malignancy is high, PD is fast and life cycle is short are so that the treatment of liver tumor is extremely urgent.The structure of liver tumor targeting drug delivery system mainly contains two kinds of strategies: passive target and active targeting, purpose all is that the targeted antitumor drug is to tumor tissues.Passive target mainly is based on the distinctive EPR effect of tumor tissues position blood vessel, and initiatively targeting then is to utilize specific head base to modify drug-supplying system, and the receptor of specific binding tumor cell surface overexpression is to reach the effect of targeted.
Studies show that, tumor cell of liver surface overexpression series of receptors, wherein TfR is used as the existing long research history of target spot.But the endogenous transferrins is dense, is about 25 μ M, can with the TfR of transferrins as the drug-supplying system of targeting head base competition tumor cell surface, thereby affect cancer target efficient.Recent research discloses the use display technique of bacteriophage and has filtered out a kind of novel polypeptide---and T7 peptide, its sequence are HAIYPRH, and be suitable to affinity and the transferrins of TfR; The T7 peptide is different from binding site and the transferrins of TfR, can not suppress and not affect with transferrins competition the physiological function of transferrins itself, phase reversal ferritin and TfR enter born of the same parents' efficient in conjunction with meeting promotion T7 peptide; In addition, T7 is micromolecule polypeptide, but chemosynthesis, good stability, sterically hindered little as targeting head base, potential applicability in clinical practice is good.
Cation high molecular material such as polyamide-amide arborization thing (polyamidoamine, be called for short PAMAM) and polylysine (dendri-graft polylysines, be called for short DGL) be the synthetic high polymer of the class Performances of Novel Nano-Porous meter level that occurs in recent years, the height branch, be monodispersity, its terminal amino group is abundant, strong electropositive, and be easy to through the suitable bioactive substances such as modification connection antibody to increase the targeting of carrier, inside has a large amount of hydrophobicity cavitys simultaneously, have the potentiality that bag carries hydrophobic anticancer drug, be expected to become good pharmaceutical carrier.
Summary of the invention
The objective of the invention is the deficiency for existing liver tumor targeting drug delivery system existence, the liver tumor-targeted nano medicine delivery that provides a kind of novel polypeptide to modify.
The present invention uses novel polypeptide to be targeting head base, and the cation high molecular material is basic macromolecule carrier, and bag carrying anti-tumor medicine is made liver tumor-targeted nano medicine delivery.
The present invention selects the novel polypeptide modified macromolecule material that filters out by display technique of bacteriophage, enters cell in the endocytosis mode, improves tumor cell to the picked-up of medicine, and safety.
The present invention has transferrins as the advantage of targeting head base, and effectively avoids the interference of endogenous transferrins, and targeting and therapeutic efficiency are high, preparation is simple and direct, and can be applied to the targeted therapy of other tumor tissues.
Purpose of the present invention is achieved through the following technical solutions:
Liver tumor-targeted nano medicine delivery of the present invention is modified by novel polypeptide and is wrapped the carrying anti-tumor medicine behind the dendrimer material again and be prepared from, the present invention is take macromolecular material, Polyethylene Glycol, polypeptide and antitumor drug as component, described component proportion is: the mol ratio of macromolecular material and Polyethylene Glycol is 1: 2～1: 40, the mol ratio of macromolecular material and polypeptide is 1: 1～1: 5, and the mol ratio of macromolecular material and antitumor drug is 1: 3～1: 40.
Described macromolecular material is selected from following macromolecule: polyamide-amide type arborization thing and polylysine.
Described Polyethylene Glycol is selected from following macromolecule: maleimide-Polyethylene Glycol 3500-butanimide (MAL-PEG3500-NHS).
Described polypeptide is selected from the novel polypeptide that display technique of bacteriophage filters out: T7 peptide, sequence are HAIYPRH.
Described antitumor drug is selected from clinically a line and Second line Drug, comprises doxorubicin hydrochloride (DOX) and paclitaxel (PTX), daunorubicin.
Targeted nanometer drug delivery system of the present invention is applicable to tumor cell of liver and other tumor cell of targeting human body source and animal origin.
The present invention prepares liver tumor-targeted nano medicine delivery as follows:
Macromolecular material is dissolved in an amount of suitable solvent is mixed with storing solution, get in right amount and in cillin bottle, dry up, take by weighing the solution that is mixed with suitable concentration in the phosphate buffer that an amount of Polyethylene Glycol is dissolved into pH value 7.8～8.2, join in the said vesse, with the macromolecular material mol ratio be 1: 2～1: 40, stirring reaction a few hours get final product under the uniform temperature, polypeptide is dissolved in an amount of phosphate buffer again, be mixed with the polypeptide solution of debita spissitudo, join in macromolecule-polyglycol solution, with the macromolecular material mol ratio be 1: 1～1: 5, react 24h under the uniform temperature, make liver tumor targeted nano carrier, transfer in MWCO 5000 ultra-filtration centrifuge tubes and remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min, again with antitumor drug with 1: 3～1: 40 stirring reaction 12h of mol ratio, transfer in MWCO 3000 ultra-filtration centrifuge tubes and remove non-encapsulated medicine with 12000rpm ultrafiltration 30min, namely get liver tumor-targeted nano medicine delivery.
The present invention possesses following outstanding advantages and feature:
But utilize the novel polypeptide T7 peptide of specific binding tumor cell of liver surface TfR to modify the cation high molecular material, make liver tumor-targeted nano medicine delivery behind the bag carrying anti-tumor medicine, give administration nano-drug administration system with the characteristic of polypeptide, make the distribution of administration nano-drug administration system have higher liver tumor targeting feature and cellular uptake feature, improve the ingestion efficiency of tumor cell of liver and the therapeutic efficiency of liver tumor;
In addition, selecting the macromolecules such as polyamide-amide arborization thing and polylysine is carrier material, is connected with polypeptid covalence, adopts Physical to prepare peptide modified liver tumor-targeted nano medicine delivery;
Preparation method of the present invention is simple, does not need special processing, can be directly used in cell and animal experiment.Liver tumor-targeted nano medicine delivery of the present invention is because peptide modified effect in the system has improved the approach that nanoparticle enters cell.The modification of polypeptide has had liver tumor-targeted nano medicine delivery to enter efficiently born of the same parents' ability, liver tumor-targeted nano medicine delivery can obtain higher tumor cell of liver ingestion efficiency within the relatively short time, and more effectively avoided other Normocellular picked-ups, improved the therapeutic efficiency of administration nano-drug administration system to liver tumor.
Description of drawings
Fig. 1 is that hydrogen nuclear magnetic resonance characterizes liver tumor targeted nano carrier PAMAM-PEG-T7.
Fig. 2 is the release conditions of antitumor drug DOX under two kinds of pH conditions.
Fig. 3 is the surface texture properties that the small angle scattering method is investigated carrier under two kinds of pH conditions.
Fig. 4 is mode of appearance and the particle diameter of atomic force microscope observation administration nano-drug administration system.
Fig. 5 is the particle size distribution of dynamic light scattering determination administration nano-drug administration system.
Fig. 6 adopts simple PAMAM-PEG-T7/DOX nanoparticle and free DOX to hatch respectively the human liver tumor cell, and sets up the plasma transferrins matched group, and absorb the result and take pictures with OLYMPUS IX 71 microscopic examinations,
Wherein, A is blank, and B is free DOX, C be the PAMAM-PEG-T7/DOX nanoparticle without transferrins, D is PAMAM-PEG-T7/DOX nanoparticle transferrins concentration 25 μ M.
Fig. 7 be adopt simple PAMAM-PEG-T7/DOX nanoparticle and free DOX respectively 48h hatch the human liver tumor cell, and set up the plasma transferrins matched group, mtt assay is measured each group to human liver tumor cell's toxicity.
Fig. 8 adopts simple PAMAM-PEG-T7/DOX nanoparticle, PAMAM-PEG/DOX nanoparticle, free DOX tail vein injection human liver tumor cell subcutaneous transplantation nude mice model, and the living imaging method is measured the distribution in each body of organizing.
Fig. 9 adopts simple PAMAM-PEG-T7/DOX nanoparticle, PAMAM-PEG/DOX nanoparticle, free DOX tail vein injection human liver tumor cell subcutaneous transplantation nude mice model, each tissue distribution behind the Syrups by HPLC 4h.
The specific embodiment
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, get 1mg and in cillin bottle, dry up, maleimide-Polyethylene Glycol 3500-butanimide (MAL-PEG3500-NHS) is dissolved in an amount of 0.035M pH 8.0 phosphate buffers is mixed with the 1mg/ml working solution.Get 242 μ l MAL-PEG3500-NHS working solutions and join in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
2) complex solution, again the T7 peptide is dissolved in an amount of pH 7.0 phosphate buffers, be mixed with the polypeptide solution of 1mg/ml, get 34.6 μ l and join PAMAM-PEG
2In the complex solution, in stirring at room reaction 24h, generate polyamide-amide-Polyethylene Glycol-polypeptide (PAMAM-PEG
2-T7
1), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, gets 1mg and in cillin bottle, dry up, MAL-PEG3500-NHS is dissolved in an amount of 0.035M pH 8.0 phosphate buffers is mixed with the 1mg/ml working solution.Get 607 μ l MAL-PEG3500-NHS working solutions and join in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
5) complex solution, again the T7 peptide is dissolved in an amount of pH 7.0 phosphate buffers, be mixed with the polypeptide solution of 1mg/ml, get 34.6 μ l and join PAMAM-PEG
5In the complex solution, in stirring at room reaction 24h, generate polyamide-amide-Polyethylene Glycol-polypeptide (PAMAM-PEG
5-T7
1), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, gets 1mg and in cillin bottle, dry up, MAL-PEG3500-NHS is dissolved in an amount of 0.035M pH 8.0 phosphate buffers is mixed with the 1mg/ml working solution.Get 1.214ml MAL-PEG3500-NHS working solution and join in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again the T7 peptide is dissolved in an amount of pH 7.0 phosphate buffers, be mixed with the polypeptide solution of 1mg/ml, get 34.6 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, generate polyamide-amide-Polyethylene Glycol-polypeptide (PAMAM-PEG
10-T7
1), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Embodiment 4.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 2.428ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
20) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 34.6 μ l and join PAMAM-PEG
20In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
20-T7
1), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Embodiment 5.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 4.856ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
40) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 34.6 μ l and join PAMAM-PEG
40In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
40-T7
1), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Embodiment 6.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.
Embodiment 7.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier.Get 1mg product 500 μ l heavy water and be dissolved in investigation Polyethylene Glycol and peptide modified ratio in the nuclear magnetic tube.
Embodiment 8.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.8ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.
Embodiment 9.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.4ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.24ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.
Embodiment 11
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.
Embodiment 12
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.06ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.
Embodiment 13
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h, remove non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, make liver tumor-targeted nano medicine delivery, join in MWCO 1000 bag filters, in pH 7.4 phosphate buffered solution and pH 5.5 acetate buffer solutions, measure the release of amycin.
Embodiment 14
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 7.4, and SAXS small angle scattering method is measured under pH 7.4 conditions scattering strength situation with the different particles of angle.
Embodiment 15
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, the pH4.5 acetate buffer redissolves, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 5.5, and SAXS small angle scattering method is measured under pH 5.5 conditions scattering strength situation with the different particles of angle.
Embodiment 16
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h, remove non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, make liver tumor-targeted nano medicine delivery, get in right amount and on mica sheet, naturally dry, atomic force microscope observation.
Embodiment 17
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h, remove non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, make liver tumor-targeted nano medicine delivery, get in right amount in PSS 380 particle diameter pipes, utilize light scattering method to characterize the particle diameter of nanoparticle.
Embodiment 18
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.In addition, adopt simple PAMAM-PEG-T7/DOX nanoparticle and free DOX to hatch respectively the human liver tumor cell, and set up the plasma transferrins matched group, with OLYMPUS IX 71 microscopic examinations picked-ups result and take pictures.
Embodiment 19
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.In addition, adopt simple PAMAM-PEG-T7/DOX nanoparticle and free DOX respectively 48h hatch the human liver tumor cell, and set up the plasma transferrins matched group, mtt assay is measured each group to human liver tumor cell's toxicity.
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.In addition, adopt simple PAMAM-PEG-T7/DOX nanoparticle, PAMAM-PEG/DOX nanoparticle, free DOX tail vein injection human liver tumor cell subcutaneous transplantation nude mice model, the living imaging method is measured the interior distribution of body of each group.
Embodiment 21
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, transfer in the cillin bottle, the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h, remove non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, make liver tumor-targeted nano medicine delivery, in addition, adopt simple PAMAM-PEG-T7/DOX nanoparticle, the PAMAM-PEG/DOX nanoparticle, free DOX tail vein injection human liver tumor cell subcutaneous transplantation nude mice model, living imaging method are measured the interior distribution of body of each group.
Embodiment 22
Polyamide-amide (PAMAM) is dissolved in the solution that is mixed with 77.35mg/ml in an amount of methanol, getting 1mg dries up in cillin bottle, NHS-PEG3500-Mal is dissolved in an amount of 0.035M pH 8.0 phosphate buffered solution is mixed with the 1mg/ml working solution, 1.214ml the Polyethylene Glycol working solution joins in the cillin bottle, 2h makes polyamide-amide-Polyethylene Glycol (PAMAM-PEG in the stirring at room reaction
10) complex solution, again T7 is dissolved in an amount of pH 7.0 phosphate buffered solution, be mixed with the polypeptide solution of 1mg/ml, get 173 μ l and join PAMAM-PEG
10In the complex solution, in stirring at room reaction 24h, with polyamide-amide-Polyethylene Glycol of making-polypeptide (PAMAM-PEG
10-T7
5), remove unreacted PEG and T7 peptide with 12000rpm ultrafiltration 30min in MWCO 5000 ultra-filtration centrifuge tubes, make liver tumor targeted nano carrier, pH 4.5 acetate buffers redissolve, and transfer in the cillin bottle, and the 1N sodium hydroxide is regulated pH to 7.4, add 1mg/ml doxorubicin hydrochloride normal saline solution 0.12ml, stirring at room reaction 12h removes non-encapsulated amycin with 12000rpm ultrafiltration 30min in MWCO 3000 ultra-filtration centrifuge tubes, makes liver tumor-targeted nano medicine delivery.In addition, adopt simple PAMAM-PEG-T7/DOX nanoparticle, PAMAM-PEG/DOX nanoparticle, free DOX tail vein injection human liver tumor cell subcutaneous transplantation nude mice model, each tissue distribution behind the Syrups by HPLC 4h.
Claims (6)
1. peptide modified liver tumor-targeted nano medicine delivery, it is characterized in that, formed by macromolecular material, Polyethylene Glycol, polypeptide and antitumor drug, wherein, described peptide modified macromolecular material forms nanoparticle, and the mol ratio of described macromolecular material and Polyethylene Glycol is 1: 2～1: 40; The mol ratio of described macromolecular material and polypeptide is 1: 1～1: 5; The mol ratio of described macromolecular material and antitumor drug is 1: 3～1: 40;
Described macromolecular material is selected from polyamide-amide type arborization thing; Described Polyethylene Glycol is selected from maleimide-Polyethylene Glycol 3500-butanimide; Described polypeptide is that sequence is the T7 peptide of HAIYPRH, and it obtains by the display technique of bacteriophage screening.
2. by peptide modified liver tumor-targeted nano medicine delivery claimed in claim 1, it is characterized in that described macromolecular material is the macromolecular material polyamide-amide type arborization thing with internal cavities.
3. by peptide modified liver tumor-targeted nano medicine delivery claimed in claim 1, it is characterized in that described antitumor drug is selected from doxorubicin hydrochloride or paclitaxel or daunorubicin.
4. by peptide modified liver tumor-targeted nano medicine delivery claimed in claim 1, it is characterized in that described sequence is that the T7 peptide specific of HAIYPRH is in conjunction with TfR.
5. the preparation method of peptide modified liver tumor-targeted nano medicine delivery claimed in claim 1 is characterized in that it comprises the steps:
Macromolecular material polyamide-amide type arborization thing is dissolved in an amount of suitable solvent methanol is mixed with storing solution, get in right amount and in cillin bottle, dry up, take by weighing the solution that is mixed with suitable concentration in the phosphate buffer that an amount of Polyethylene Glycol maleimide-Polyethylene Glycol 3500-butanimide is dissolved into pH value 7.8～8.2, join in the said vesse, with macromolecular material polyamide-amide type arborization thing mol ratio be 1:2～1:40, stirring reaction is after a few hours under the uniform temperature, polypeptide HAIYPRH is dissolved in an amount of phosphate buffer, be mixed with the polypeptide HAIYPRH solution of debita spissitudo, join in macromolecular material polyamide-amide type arborization thing-Polyethylene Glycol maleimide-Polyethylene Glycol 3500-butanimide solution, with macromolecular material polyamide-amide type arborization thing mol ratio 1:1～1:5, react 24h under the uniform temperature, make liver tumor targeted nano carrier, transfer in MWCO 5000 ultra-filtration centrifuge tubes and remove unreacted Polyethylene Glycol 3500 and polypeptide HAIYPRH with 12000rpm ultrafiltration 30min, again with antitumor drug with mol ratio 1:3 ~ 1:40 stirring reaction 12h, transfer in MWCO 3000 ultra-filtration centrifuge tubes and remove non-encapsulated medicine with 12000rpm ultrafiltration 30min, namely get liver tumor-targeted nano medicine delivery.
6. the purposes of the peptide modified liver tumor-targeted nano medicine delivery of claim 1 in the tumor cell of liver medicine of preparation targeted therapy human body source or animal origin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101984505A CN102048694B (en) | 2009-11-06 | 2009-11-06 | Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101984505A CN102048694B (en) | 2009-11-06 | 2009-11-06 | Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102048694A CN102048694A (en) | 2011-05-11 |
| CN102048694B true CN102048694B (en) | 2013-03-13 |
Family
ID=43953718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101984505A Expired - Fee Related CN102048694B (en) | 2009-11-06 | 2009-11-06 | Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102048694B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145798B (en) * | 2012-06-07 | 2014-09-10 | 中国科学技术大学 | Polypeptide of specific binding rare earth nanoparticle and screening method thereof |
| CN103705465B (en) * | 2012-10-09 | 2016-01-13 | 复旦大学 | Cancer target administration nano-drug administration system that a kind of micro-acid environment target polypeptide is modified and preparation method thereof |
| CN103705464B (en) * | 2012-10-09 | 2015-10-07 | 复旦大学 | A kind of micro-acid environment controls tumor-targeting administration nano-drug administration system opened and preparation method thereof |
| CN104415338B (en) * | 2013-09-09 | 2018-04-10 | 中国科学院宁波材料技术与工程研究所 | Active targeting type antineoplastic and preparation method thereof |
| CN103908677B (en) * | 2014-04-04 | 2017-02-01 | 南京医科大学 | Tumor targeted polypeptide-adriamycin amycin derivative as well as preparation method and application thereof |
| CN109954144B (en) * | 2017-12-14 | 2022-07-08 | 复旦大学 | Two-stage pH response nanoparticle based on modified poly beta-amino ester material and preparation method thereof |
| KR102209906B1 (en) * | 2019-07-08 | 2021-02-01 | 주식회사 라이센텍 | Oncolytic T7 bacteriophage having cytokine gene and displaying homing peptide on capsid and its use for treating cancer |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6743893B2 (en) * | 2000-11-30 | 2004-06-01 | The Uab Research Foundation | Receptor-mediated uptake of peptides that bind the human transferrin receptor |
| CN1631936A (en) * | 2003-12-24 | 2005-06-29 | 上海市血液中心 | Polyamide-amine type branch-shape polymer nano materials, synthesis method and use thereof |
| CN1743008A (en) * | 2005-09-23 | 2006-03-08 | 南开大学 | Method for preparing nano liver-target biodegradating medicine carrier material |
| CN1872348A (en) * | 2006-04-17 | 2006-12-06 | 华东师范大学 | Ligand of polyoxyethylene of containing target peptide toward to liver cancer |
| CN101225190A (en) * | 2008-01-25 | 2008-07-23 | 陕西科技大学 | Hydrophobic method for polyamide polyamine/starch blend |
| CN101234122A (en) * | 2008-03-03 | 2008-08-06 | 中国科学院化学研究所 | New purpose of polylysine |
| WO2009008727A2 (en) * | 2007-07-12 | 2009-01-15 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs or tissues |
| CN101361978A (en) * | 2008-09-02 | 2009-02-11 | 浙江大学 | Anti-cancer medicine release system using cellular membrane biomimetic modification polyamide-amide as carrier and preparation method thereof |
-
2009
- 2009-11-06 CN CN2009101984505A patent/CN102048694B/en not_active Expired - Fee Related
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6743893B2 (en) * | 2000-11-30 | 2004-06-01 | The Uab Research Foundation | Receptor-mediated uptake of peptides that bind the human transferrin receptor |
| CN1631936A (en) * | 2003-12-24 | 2005-06-29 | 上海市血液中心 | Polyamide-amine type branch-shape polymer nano materials, synthesis method and use thereof |
| CN1743008A (en) * | 2005-09-23 | 2006-03-08 | 南开大学 | Method for preparing nano liver-target biodegradating medicine carrier material |
| CN1872348A (en) * | 2006-04-17 | 2006-12-06 | 华东师范大学 | Ligand of polyoxyethylene of containing target peptide toward to liver cancer |
| WO2009008727A2 (en) * | 2007-07-12 | 2009-01-15 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs or tissues |
| CN101225190A (en) * | 2008-01-25 | 2008-07-23 | 陕西科技大学 | Hydrophobic method for polyamide polyamine/starch blend |
| CN101234122A (en) * | 2008-03-03 | 2008-08-06 | 中国科学院化学研究所 | New purpose of polylysine |
| CN101361978A (en) * | 2008-09-02 | 2009-02-11 | 浙江大学 | Anti-cancer medicine release system using cellular membrane biomimetic modification polyamide-amide as carrier and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 胡海梅.半乳糖-聚乙二醇-聚-L-赖氨酸质粒pEGFP-C1复合物纳米胶束的制备和性能研究.《半乳糖-聚乙二醇-聚-L-赖氨酸质粒pEGFP-C1复合物纳米胶束的制备和性能研究》.2006,全文. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102048694A (en) | 2011-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer | |
| CN102048694B (en) | Polypeptide-modified liver tumor-targeted nano medicine delivery system and preparation method thereof | |
| CN102740895B (en) | Nanoconjugate and nanoconjugate preparation | |
| Zhang et al. | Dendrimer grafted persistent luminescent nanoplatform for aptamer guided tumor imaging and acid-responsive drug delivery | |
| EP2860193B1 (en) | Polypeptide with function of targeted diagnosis and therapy of nasopharyngeal carcinoma, nanoparticles carrying same and use thereof | |
| CN107789632A (en) | A kind of active Brain targeting nanoscale medicine delivery system of T7 peptides modification and preparation method thereof | |
| Wang et al. | Cetuximab conjugated and doxorubicin loaded silica nanoparticles for tumor-targeting and tumor microenvironment responsive binary drug delivery of liver cancer therapy | |
| CN107184987B (en) | Lipoic acid modified targeted integrin alpha v beta 3 nano-polypeptide carrier and preparation method and application thereof | |
| Shao et al. | A smart multifunctional nanoparticle for enhanced near-infrared image-guided photothermal therapy against gastric cancer | |
| Yang et al. | Tumor-targeted biodegradable multifunctional nanoparticles for cancer theranostics | |
| CN102397564B (en) | Tumor-targeted diagnosis nuclear magnetic resonance contrast agent and preparation method thereof | |
| CN108339124B (en) | Preparation method and application of two-stage brain-targeted polymer micelle drug delivery system | |
| KR20100094664A (en) | A tumor targeting protein conjugate and a method for preparing the same | |
| Lin et al. | Doxorubicin loaded silica nanoparticles with dual modification as a tumor-targeted drug delivery system for colon cancer therapy | |
| Xing et al. | Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer | |
| Xiao et al. | A dendrimer-based dual radiodense element-containing nanoplatform for targeted enhanced tumor computed tomography imaging | |
| CN114748639A (en) | Photosensitizer-hydroxyalkyl starch-polypeptide coupled amphiphilic macromolecular compound, nano drug delivery system and preparation method thereof | |
| CN101249266B (en) | Nano liver target direction amphipathic nature block copolymers drug administration system and preparation | |
| Li et al. | Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy | |
| CN101337076A (en) | Functional dendritic polymer gene vector system of targeted malignant cerebroma | |
| CA3045367A1 (en) | Vap polypeptide and use thereof in preparation of drug for targeted diagnosis and treatment of tumour | |
| CN101234205B (en) | High molecule adriamycin bonding medicine nano capsule with targeting function and preparation thereof | |
| Wang et al. | Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer | |
| US20130302255A1 (en) | Novel targeted paramagnetic contrast agent | |
| CN106880846B (en) | Tumor-targeted multifunctional nano drug delivery system, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130313 Termination date: 20151106 |
|
| EXPY | Termination of patent right or utility model |