CN115433354B - Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex - Google Patents
Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex Download PDFInfo
- Publication number
- CN115433354B CN115433354B CN202210987175.0A CN202210987175A CN115433354B CN 115433354 B CN115433354 B CN 115433354B CN 202210987175 A CN202210987175 A CN 202210987175A CN 115433354 B CN115433354 B CN 115433354B
- Authority
- CN
- China
- Prior art keywords
- drug
- self
- amphiphilic block
- block polymer
- entrapped
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/3311—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group
- C08G65/3314—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic
- C08G65/3315—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic aromatic
- C08G65/3317—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing a hydroxy group cyclic aromatic phenolic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/337—Polymers modified by chemical after-treatment with organic compounds containing other elements
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G2650/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterized by the type of post-polymerisation functionalisation
- C08G2650/04—End-capping
Abstract
The invention discloses an amphiphilic block polymer, self-assembled nano particles, a medicine-entrapped complex prepared from the amphiphilic block polymer and application thereof, relates to a medicine high-molecular polymer, and aims to solve the problems of poor sensitivity response or less medicine-entrapped complex, slow medicine release and the like, and the technical scheme is as follows: the hydrophilic and lipophilic groups are connected through aryl borate groups, and self-assembled nano particles are formed to wrap the anticancer drugs to form a drug-loaded complex. The polymer can be self-assembled into nano particles in water environment, has the capability of encapsulating drugs, can encapsulate anti-tumor drugs, and can be targeted released in the tumor environment with high ROS expression, thereby achieving the effect of high-efficiency treatment, effectively improving the bioavailability of the drugs, avoiding the toxic and side effects of the chemotherapeutics, and overcoming the problems of poor water solubility of the chemotherapeutics and the like.
Description
Technical Field
The invention relates to a medical high molecular polymer, in particular to an ROS responsive amphiphilic block polymer, self-assembled nano particles, a medicine-entrapped complex prepared from the same and application of the medicine-entrapped complex.
Background
It is well known that ROS levels in the tumor environment are highly expressed due to the faster proliferation of tumor cells. This highly expressed ROS is one of the differences between normal cellular environment and tumor cellular environment. Thus, with this difference, more and more ROS-responsive drugs, nanoparticles, liposomes, etc. are being studied and developed for the treatment of cancer. The main characteristic of the medicines is that the medicines can be kept stable in normal cell environment, and when encountering tumor environment with high ROS expression, the medicines are released, so that the purpose of targeted therapy is achieved, and the problems of great toxic and side effects of general chemotherapeutics, damage to normal tissues and the like are reduced.
In recent years, more and more responsive nano-drug carriers are researched and developed, including pH, enzyme and ROS responsive drug carriers, wherein the drug carriers responding to ROS are relatively more, but many of the drug carriers have the problems of poor sensitivity responsiveness or less drug-entrapped, slow drug release and the like. Moreover, more and more antitumor drugs face the problems of cell resistance, poor solubility, short half-life, insignificant effect and the like.
Therefore, the novel nano drug delivery system targeting the tumor microenvironment is designed and constructed, the treatment effect of the drug is improved, the drug resistance is overcome, the toxic and side effects are reduced, and the method has good scientific significance and clinical value.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention aims to provide an amphiphilic block polymer, wherein a lipophilic and hydrophilic part of the amphiphilic block polymer is connected with a boric acid ester structure through a chemical bond, and the structure has the characteristic of responsive fracture in an ROS environment. The polymer can be self-assembled into nano particles in water environment, has the capability of encapsulating drugs, can encapsulate anti-tumor drugs, and can be targeted released in the tumor environment with high ROS expression, thereby achieving the effect of high-efficiency treatment, effectively improving the bioavailability of the drugs, avoiding the toxic and side effects of the chemotherapeutic drugs, and overcoming the problems of poor water solubility of the chemotherapeutic drugs and the like.
The technical aim of the invention is realized by the following technical scheme: an amphiphilic block polymer characterized by: the hydrophilic and lipophilic groups are linked by an arylboronic acid ester group, the structure of which is:
the invention is further provided with: the hydrophilic group is polyethylene glycol (PEG) and polylactic acid, and the lipophilic group is various long-chain saturated fatty acids, unsaturated fatty acids and cholesterol.
A self-assembled nanoparticle is formed by self-assembling amphiphilic block polymers in water environment.
By adopting the technical scheme, the self-assembled nanoparticle can stably exist in a normal environment, but can quickly respond in an ROS environment and decompose, and has the characteristic of very sensitive responsiveness.
A composite for encapsulating medicine is prepared from self-assembled nanoparticles and the insoluble antineoplastic medicine.
By adopting the technical scheme, the polymer has the capability of carrying the medicine in the water environment, and the medicine-carrying complex can rapidly release the medicine in the ROS environment and slowly release the medicine in the normal body fluid environment.
The invention is further provided with: the antitumor drug comprises 10-hydroxycamptothecin and doxorubicin.
The invention is further provided with: the self-assembled nanoparticle is decomposed and targeted for release in a tumor environment with high ROS expression.
Use of a drug-loaded complex according to claim 4 or 5, wherein: the drug-loaded complex is applied to the treatment of colon cancer and lung cancer diseases.
By adopting the technical scheme, the test result shows that the complex of the entrapped medicine has no obvious toxicity to normal cells and has obvious inhibition effect to tumor cells. Can obviously promote apoptosis of tumor cells and has good tumor inhibition effect.
In summary, the invention has the following beneficial effects:
the amphiphilic block polymer is designed and synthesized to form an amphiphilic polymer, the polymer can be self-assembled in water environment to form stable self-assembled nanoparticles, the self-assembled nanoparticles have the capability of being released by cracking under the condition of H2O2, and the problems of poor water solubility, large side effect, insignificant treatment effect and the like of the drug are overcome by targeted delivery of experimental drugs.
Drawings
FIG. 1 is a synthetic route and cleavage mechanism under ROS environment for the amphiphilic block polymer of example 1, showing cleavage of the polymer;
FIG. 2 shows the particle size measurement data of self-assembled nanoparticles and the effect of a scanning electron microscope;
FIG. 3 is a graph showing stability and responsiveness data of self-assembled nanoparticles for different H' s 2 O 2 Particle size variation under conditions;
FIG. 4 is in vitro simulated drug release data of drug-loaded complexes showing the drug-loaded complexes at different H' s 2 O 2 Simulating drug release conditions under the conditions;
FIG. 5 shows the inhibition effect of the drug-loaded complex on normal human cells and tumor cells, showing the killing effect of the drug-loaded complex on normal cells and tumor cells;
FIG. 6 is the effect of drug-loaded complexes on apoptosis of human colon cancer cells.
Detailed Description
The present invention will be described in detail below with reference to the accompanying drawings and examples.
Example 1 Process for the preparation of Polymer
3g of 2-hydroxy-5-methyl-1, 3-benzenedimethanol (2, 6-Bis (Hydroxymethyl) -4-Methylphenol) (1.0 eq), 2.67g of imidazole (Glyoxaline) (2.2 eq) were dissolved in 8ml of DMF, followed by stirring at 0℃and 6.08g of Tert-butyldimethylsilyl chloride (TBDMSCL) (technical-butylmethylcellobiosilane) (2.26 eq) were dissolved in DMF, and the mixture was slowly dropped into the reaction system, and after the completion of the dropping, R.T. reaction was followed by TLC monitoring and reaction was completed for 5 hours. The reaction was extracted three times with saturated NaCl solution, EA, the organic layers were combined, dried over MgSO4, and the solution was suction-filtered. Then separated by silica gel column and passed out the point of the product by PE to give the product as colorless oily liquid (92%).
The starting material (1.0 eq) for the reaction was dissolved in 10ml of anhydrous DMF, then stirred at 0deg.C, K2CO3 (1.5 eq) 2.09g of solid was slowly added, stirred for 10min, then 4-bromomethylphenylboronic acid pinacol ester (4-Bromomethylphenylboronic acid pinacol ester) (1.1 eq) 3.27g was slowly added at 0deg.C, after the addition was completed, the reaction was transferred to 50deg.C for 2h, monitored by TLC, and the starting material was complete. The reaction was extracted three times with saturated NaCl solution, EA, the organic layers were combined, dried over MgSO4, and the solution was suction-filtered. Then separated by silica gel column and passed out the point of the product by PE to give the product as colorless oily liquid (66%).
Raw material (1.0 eq) 4.9g was dissolved in 10ml of methanol, stirred at r.t. and then p-toluenesulfonic acid monohydrate (p-Toluenesulfonic acid monohydrate) (0.19 eq) 0.3g was added and monitored by tlc, and the reaction was completed for 2 h. The reaction system was dried in vacuo, then purified by column chromatography on silica gel, and purified by PE: ea=2:1 over product, yield a white solid (88%).
1.1g of raw material (1.0 eq) and 0.88g of Stearic acid (Stearic acid) (1.2 eq) were added to a three-necked flask, dissolved in DCM, and the whole system was protected with N2. Then, 0.74g of edc.hcl (1..5 eq), 0.065g of et3n (0.25 eq) were dissolved in DCM, and then 0.063g of DMAP (0.2 eq) was dissolved in DCM by syringe and added to the reaction system, followed by r.t. reaction, TLC monitoring, 5h reaction, and completion of the reaction. The reaction was extracted three times with DCM and the organic layers were combined, dried over MgSO4 and the solution was spun-dried by suction filtration. Purification by silica gel column, PE: ea=20:1 over-substitution points and impurities, with PE: ea=5:1 isolation and purification gave the product as a colourless oil, 0.56g (33%).
Raw material 4 (1.0 eq) 20mg and PEG-COOH (1K) (0.5 eq) 320mg were added to a three-necked flask, dissolved in DMSO, and then the whole system was protected with N2. Then, 9.47mg of EDC. HCl (1..5 eq.) and 0.842mg of Et3N (0.25 eq.) were dissolved in DMSO, and then 0.813mg of DMAP (0.2 eq.) was dissolved in DMSO by adding to the reaction system by syringe, and then the mixture was reacted for 110 hours. The reaction system was dialyzed against ultrapure water using a dialysis bag of 1.0KD, water was changed every 4 hours, and the reaction system was dialyzed for 48 hours to remove unreacted small molecules. And then freeze-dried.
Example 2 self-assembled nanoparticle Property measurement
5mg of PEG-1000 material was precisely weighed and dissolved in 1ml of DMSO, respectively, and slowly dropped into 20ml of PBS under high-speed stirring, and the dropping was stopped. The particle size was then measured. Then, the change in particle size under the conditions of response and control at H2O2 concentrations of 0mmol,0.05mmol,0.1mmol,1mmol,2mmol,5mmol was monitored.
EXAMPLE 3 preparation of drug-loaded Complex and simulated drug Release
10mg of PEG material was dissolved in 1ml of DMSO, 6mg of HCPT was weighed and dissolved in 1ml of DMSO, the two parts were aliquoted, mixed and shaken, and added to 20ml of PBS under high-speed stirring by using a rubber head dropper, and stirring was started for 4h, 17.10. Dialysis was performed with 1000KD dialysis bags for 24h, with water changing every 4 h. The liquid was lyophilized.
Example 4 measurement of cytostatic Effect
The digestion was stopped by pancreatin digestion of HCT116 cells for 2min, and addition of medium containing 10% serum. The mixed cells were then gently swirled and exponentially growing HCT116 cells were seeded at 5000 cells/well in 96-well plates. After 24h incubation, the cells were treated individually or cooperatively with 10-Hydroxycamptothecin (HCPT), DE or DEH at the indicated concentrations and then cultured continuously for 48h. Add 25. Mu.l MTT solution directly to each well and continue incubation for an additional 3h. The absorbance of the optical concentration was measured with a microplate reader (Sunrise, tecan) having a wavelength of 490 nm. Cell viability was calculated by the following formula: cell viability (%) = (average absorbance of treated group-average absorbance of blank)/(average absorbance of untreated group-average absorbance of blank) ×100%. Normal cell assays were as described above.
EXAMPLE 5 determination of apoptosis in tumor cells
HCT116 cells were plated on 6-well plates for 24 hours and then treated with varying concentrations of DEH (36.2,72.4 or 144.8 μg/ml), NAC (5 μm), nac+deh (5 μm+144.8 μg/ml) or DMSO for 36 hours. Cells were collected, washed twice with ice-cold PBS, and then analyzed by flow cytometry (FACSCalibur flow cytometer; BD Biosciences), apoptosis was assessed by staining with FITC-conjugated annexin V and PI in binding buffer for 30 minutes.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above examples, and all technical solutions belonging to the concept of the present invention belong to the protection scope of the present invention. It should be noted that modifications and adaptations to the present invention may occur to one skilled in the art without departing from the principles of the present invention and are intended to be within the scope of the present invention.
Claims (5)
1. An amphiphilic block polymer characterized by: the hydrophilic and lipophilic groups are connected through arylborate groups, the preparation flow is shown as follows, and the structure of the polymer is shown as a formula (1):
2. a nanoparticle prepared by self-assembly, characterized in that: formed from self-assembly of the amphiphilic block polymer of claim 1 in an aqueous environment.
3. A pharmaceutical entrapped complex, characterized by: a nanoparticle prepared by the self-assembly of claim 2 and an entrapped poorly soluble anti-tumor drug.
4. A drug-entrapped complex according to claim 3, characterized in that: the antitumor drug comprises 10-hydroxycamptothecin and doxorubicin.
5. A drug-entrapped complex according to claim 3, characterized in that: the nanoparticle is decomposed and targeted for release in the tumor environment where ROS is highly expressed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210987175.0A CN115433354B (en) | 2022-08-17 | 2022-08-17 | Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210987175.0A CN115433354B (en) | 2022-08-17 | 2022-08-17 | Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115433354A CN115433354A (en) | 2022-12-06 |
| CN115433354B true CN115433354B (en) | 2023-09-12 |
Family
ID=84243512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210987175.0A Active CN115433354B (en) | 2022-08-17 | 2022-08-17 | Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115433354B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI225870B (en) * | 2000-02-09 | 2005-01-01 | Ciba Sc Holding Ag | Hyperbranched amphiphilic polymeric additives and polymer compositions with increased surface energy |
| CN105273205A (en) * | 2015-10-09 | 2016-01-27 | 华东师范大学 | Block polymer with benzeneboronic acid ester as connecting unit, synthesis method and application thereof |
| CN108478531A (en) * | 2018-05-21 | 2018-09-04 | 中国医学科学院生物医学工程研究所 | Folate-targeted restores sensitive medicament-carried polymer nano micelle and its preparation method and application |
| US10517823B1 (en) * | 2016-08-10 | 2019-12-31 | Verily Life Sciences Llc | ROS—responsive liposomes for specific targeting |
| CN113633625A (en) * | 2021-05-19 | 2021-11-12 | 河南大学 | Nano-drug of hybrid membrane loaded oxidative phosphorylation inhibitor and preparation method thereof |
| CN113925841A (en) * | 2020-07-09 | 2022-01-14 | 中国科学技术大学 | High-drug-loading-efficiency nano-particles and preparation and application thereof |
| CN113995850A (en) * | 2021-09-30 | 2022-02-01 | 浙江大学杭州国际科创中心 | Tyrosinase response cascade amplification nano-drug and preparation and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9333264B2 (en) * | 2013-03-06 | 2016-05-10 | The Regents Of The University Of California | Biocompatible polymeric nanoparticles degrade and release cargo in response to biologically relevant levels of hydrogen peroxide |
-
2022
- 2022-08-17 CN CN202210987175.0A patent/CN115433354B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI225870B (en) * | 2000-02-09 | 2005-01-01 | Ciba Sc Holding Ag | Hyperbranched amphiphilic polymeric additives and polymer compositions with increased surface energy |
| CN105273205A (en) * | 2015-10-09 | 2016-01-27 | 华东师范大学 | Block polymer with benzeneboronic acid ester as connecting unit, synthesis method and application thereof |
| US10517823B1 (en) * | 2016-08-10 | 2019-12-31 | Verily Life Sciences Llc | ROS—responsive liposomes for specific targeting |
| CN108478531A (en) * | 2018-05-21 | 2018-09-04 | 中国医学科学院生物医学工程研究所 | Folate-targeted restores sensitive medicament-carried polymer nano micelle and its preparation method and application |
| CN113925841A (en) * | 2020-07-09 | 2022-01-14 | 中国科学技术大学 | High-drug-loading-efficiency nano-particles and preparation and application thereof |
| CN113633625A (en) * | 2021-05-19 | 2021-11-12 | 河南大学 | Nano-drug of hybrid membrane loaded oxidative phosphorylation inhibitor and preparation method thereof |
| CN113995850A (en) * | 2021-09-30 | 2022-02-01 | 浙江大学杭州国际科创中心 | Tyrosinase response cascade amplification nano-drug and preparation and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115433354A (en) | 2022-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10188605B2 (en) | Nanoparticles and nanoparticle compositions | |
| CN102060991B (en) | Amphiphilic prodrug of 7- ethyl-10-hydroxycamptothecin and preparation method thereof | |
| CN110591078B (en) | Preparation method of reduction/pH dual-responsiveness adriamycin prodrug | |
| CN107936058B (en) | Docetaxel derivative and preparation method and application thereof | |
| CN111330014B (en) | Acid-responsive cross-linked polymer prodrug and preparation method and application thereof | |
| CN112843241B (en) | Bioresponsible nitric oxide donor polymer prodrugs and methods of making same | |
| CN109288813B (en) | Selenium-containing taxol dimer prodrug polymer nanoparticles and preparation method thereof | |
| CN110746598B (en) | Completely degradable GSH/ROS double-sensitive polymer and preparation method and application thereof | |
| CN112494458B (en) | Construction of triglyceride-like prodrug intravenous injection self-assembly nanoparticles | |
| CN110251685B (en) | Synthesis method and application of taxol-berberine nano-drug | |
| Soleimani et al. | Photodegradable poly (ester amide) s for indirect light-triggered release of paclitaxel | |
| CN111333786B (en) | Preparation method of acid-sensitive adriamycin prodrug based on zwitterion and folic acid targeting | |
| US20180303949A1 (en) | Water-soluble docetaxel anticancer drug compound and preparation method and use thereof | |
| CN115433354B (en) | Amphiphilic block polymer, self-assembled nanoparticle, drug-entrapped complex prepared from amphiphilic block polymer and application of drug-entrapped complex | |
| CN108635590B (en) | PH-responsive polysaccharide-bortezomib nanosphere and preparation method and application thereof | |
| CN111202850A (en) | Camptothecin prodrug and preparation method and application thereof | |
| CN111592605A (en) | Hyaluronic acid-cystamine-oleic acid polymer and application thereof in drug delivery | |
| CN113398276B (en) | Preparation and application of brain glioma targeted berberine and folic acid modified lipid material | |
| CN103055321A (en) | Methoxy polyethylene glycol-polyphosphate diblock copolymer and adriamycin bonding medicine thereof | |
| CN104892807A (en) | Surface saccharide-modified polymer micelle, and preparation method and application thereof | |
| WO2007145455A1 (en) | Water soluble micelle-forming and biodegradable cyclotriphosphazene-taxol conjugate anticancer agent and preparation method thereof | |
| Jun et al. | A micellar prodrug of paclitaxel conjugated to cyclotriphosphazene | |
| Qiao-Ling et al. | Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with lactosylnorcantharidin phospholipid complex: Preparation, characterization, and therapeutic evaluation in vivo and in vitro | |
| CN107744503B (en) | Preparation method of enzyme-sensitive amphiphilic polyester MePEG-Peptide-PER-CL administration nanoparticle | |
| CN116120333B (en) | Podophyllotoxin nano prodrug and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |