CN103622915A - Targeting nanometer drug delivery system aiming at glioma - Google Patents
Targeting nanometer drug delivery system aiming at glioma Download PDFInfo
- Publication number
- CN103622915A CN103622915A CN201210306978.1A CN201210306978A CN103622915A CN 103622915 A CN103622915 A CN 103622915A CN 201210306978 A CN201210306978 A CN 201210306978A CN 103622915 A CN103622915 A CN 103622915A
- Authority
- CN
- China
- Prior art keywords
- delivery system
- glioma
- polyethylene glycol
- cerebral glioma
- targeted nano
- 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.)
- Granted
Links
Images
Abstract
The invention belongs to the field of medicine preparation, and in particular to a targeting nanometer drug delivery system aiming at glioma, and a preparation method and application thereof. The drug delivery system comprises target functional molecules, a drug and nano carriers. The target functional molecules are from short chain polypeptide from interleukin 13; the drug is a micromolecular anti-glioma drug; the nano carriers are liposome with surface modified by polyethylene glycol, nanoparticles, polymeric vesicles, polymer micelles and solid lipid nanoparticles; and the drug is enveloped in the nano carriers in an enveloping or covalent connection manner, and the short chain polypeptide is connected with the polyethylene glycol on the surfaces of the nanoparticles through covalent connection. The drug delivery system can promote uptake of the glioma cells by mediated effect of an interleukin 13 receptor alpha 2 on the surfaces of the glioma cells, so as to improve the effect of anti-glioma chemotherapeutics.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to cancer target and pass medicine research, be specifically related to a kind of targeted nano delivery system for cerebral glioma and its preparation method and application.
Background technology
Malignant glioma has become affects one of the brain of human health major disease, report according to statistics, and it has very high mortality rate, and 5 years survival rates of adult's malignant glioma are lower than 5%, but there is no at present the way of effective healing.For malignant glioma, traditional Therapeutic Method is to adopt antitumor drug to carry out chemotherapy after ocal resection again.Yet excision is very risky, and most of traditional antitumor drug does not have selectivity, when killing tumor cell, can cause lethal effect to normal cell yet, causes serious side effect and its application is restricted.
At present, nano target delivery system is one of focus of antitumor drug research and development.The antitumor research of nanoscale medicine delivery system is devoted in a large amount of research and invention, to improve the antitumous effect of medicine, reduces the toxic and side effects of medicine.As patent " nano-micelle preparations of the anthracene nucleus antineoplastic antibiotic that polyglycol derivatization phospholipid bag carries " (number of patent application 200510059621.8), " nano-micelle preparations of the catharanthus roseus alkaloids anti-tumor medicaments that polyglycol derivatization phospholipid bag carries " (number of patent application 200510098381.2), " preparation method that suppresses the composite nano-polymers of multi-drug resistance of the tumor " (number of patent application 200610096365.4), " a kind of tumour-specific targeting drug delivery system and the application in preparing medicine for treating tumor thing thereof " (number of patent application 02105456.8).And, the preparation listing of existing part nano target delivery system, as Evacet, paclitaxel albumin nano granular.Nano target delivery system treatment tumor main advantage is embodied in following 2 points: first, nanoscale medicine delivery system is by the distribution that enhancing sees through and delay (EPR) effect has improved tumor locus of tumor locus, reduced the distribution of non-target site, improve the action effect of medicine, reduced the toxic and side effects of medicine; Second, some normal cell of the normal specificity overexpression of tumor cell surface is not expressed or receptor or the albumen of low expression, on nanoscale medicine delivery system surface, connect a target function molecule, the combination of the specific receptor by target function molecule and tumor cell surface, can significantly improve tumor cell for the picked-up of medicine, improve the antitumous effect of nanoscale medicine delivery system.
Prior art discloses Interleukin-13 receptor I α 2(L13R α 2) be interleukin-11 3(IL13) one of receptor, on kinds of tumor cells surface, have specific expressedly, there is very high affinity with interleukin-11 3.Research discovery, the expression of IL23R α 2 has significant samples of human glioma specificity: only express the glioma in astrocyte source, and normal brain tissue cell is not expressed or trace is expressed; And IL13R α 2 is relevant to the grade of malignancy of astrocytoma, and have closely related with the generation development of astrocytoma.Therefore, IL13R α 2 is considered to new glioma mark of correlation thing, can be used for targeting diagnosis and the treatment of glioma.There is research to confirm IL13 and toxic protein molecule construction fusion rotein, by IL13R α 2 combinations of IL13 and tumor surface, lps molecule targeting is imported in tumor cell, play the effect of killing tumor cell.As people IL13 and Pseudomonas exotoxin (PE) are formed to fusion rotein IL13PE38QQR, IL13PE38QQR just can kill glioma cell in extremely low concentration, and its toxic action can be blocked by excessive IL13, the cytotoxic effect of prompting IL13R α 2 mediations is special.Because normal brain tissue cell is expressed IL13R α 2 hardly, so IL13PE38QQR does not show obvious toxicity or there is no toxicity these cells.Pharmacodynamics test also confirms, IL13PE38QQR has good therapeutic effect to lotus glioblastoma Mus, does not find obvious toxic and side effects.Due to the acquired clinical front experimental result preferably of IL13PE38QQR, be used to I/II clinical and experimental study of the glioblastoma patient of recurrence.
Although it is the method for approving in the industry that construction of fusion protein is realized the targeted therapy of glioma, remain in following shortcoming: (1) fusion rotein may reduce the affinity of IL13 and IL13R α 2, also likely reduce the activity of toxin protein simultaneously; (2) stably express of fusion rotein and purification difficulty are large, and production cost is high; (3) receptor of IL13 is more, fusion rotein may targeting non-target site cell, cause the toxic and side effects of normal tissue cell; (4) the quiet notes Half-life in vivo of fusion rotein is short, and medicine is less in the distribution of tumor locus.IL13 peptide (sequence is VDKLLLHLKKLFREGQFNRNFESIIICRDR) is the short peptide sequence that derives from IL13, has very high affinity with IL13R α 2, and is not combined with other receptor of IL13.Have no at present the report of IL13 peptide decorated nanometer delivery system treatment cerebral glioma both at home and abroad.
For obtaining better glioma targeting, significantly improve tumor cell for the picked-up of medicine, improve the antitumous effect of medicine.The present invention intends adopting IL13 peptide decorated nanometer delivery system, by the IL13R α 2 on selectively targeted glioma cell surface, promotes the picked-up of tumor cell, improves the antitumous effect of chemotherapeutics.
Summary of the invention
The object of the invention is to the deficiency existing for prior art, a kind of nanoscale medicine delivery system for cerebral glioma is provided, be specifically related to the nanoscale medicine delivery system that IL13 peptide is modified.This delivery system can pass through the mediation of brain glioblastoma cell surface receptor IL13R α 2, promotes the picked-up of tumor cell, improves the antitumous effect of chemotherapeutics.
Particularly, it is characterized in that, comprise target function molecule, medicine and nano-carrier, described target function molecule is the small peptide (IL13) that derives from interleukin-11 3, described medicine is micromolecule antitumor drug, and described nano-carrier is polyethyleneglycol modified liposome, nanoparticle, polymer vesicle, polymer micelle or solid lipid nanoparticle of surface; Described medicine is loaded in nano-carrier with parcel or covalently bound mode bag, and described small peptide is connected with the Polyethylene Glycol on nanoparticle surface by covalently bound mode.
In the present invention, the described small peptide aminoacid sequence that derives from IL13 is VDKLLLHLKKLFREGQFNRNFESIIICRDR.
In the present invention, the molecular weight of nano-carrier surface Polyethylene Glycol is 1000-20000Da, preferably 2000-5000Da; Above-mentioned Polyethylene Glycol can be mono methoxy polyethylene glycol, or contains the Polyethylene Glycol of other active group; Above-mentioned active group is selected from a kind of in maleimide base, sulfydryl, amido, carboxyl, biotin or Avidin.
In the present invention, described targeted nano delivery system particle diameter is 10-300nm, preferably 50-150nm.
In the present invention, micromolecule antitumor drug is selected from a kind of in taxanes, Anthraquinones, camptothecin, vinca.
Object of the present invention is achieved through the following technical solutions:
1, take polyethylene glycol-caprolactone (PEG-PCL) is material, adopt the preparation of emulsifying lyase evaporation to carry Docetaxel nanoparticle (DTX-NP), IL13 peptide is connected and obtains DTX-ILNP with carboxyl-PEG covalency on nanoparticle surface, Zeta/ laser particle analyzer is measured mean diameter and the current potential of nanoparticle, its form of transmission electron microscope observing;
2, external glioma cell apoptosis test, the targeted therapy effect of the drug-carrying nanometer particle that cellular level evaluation IL13 peptide is modified to glioma cell;
3, by external glioma ball growth inhibited, test the therapeutic effect of the drug-carrying nanometer particle that evaluation IL13 peptide is modified to external glioma ball;
4, with after IR dyes Dir marking nano grain, the targeting of the nanoparticle of evaluating the modification of IL13 peptide by living imaging to cerebral glioma;
5, by anti-glioma in body, test the therapeutic effect of the drug-carrying nanometer particle that evaluation ILI3 peptide is modified to lotus glioma Mus.
Outstanding advantages of the present invention is that this delivery system, by the mediation of brain glioblastoma cell surface Interleukin-13 receptor α 2, promotes the picked-up of brain glioblastoma cell, effectively realizes the targeted therapy of cerebral glioma, improves the anti-cerebral glioma effect of chemotherapeutics.
For the ease of understanding, below the drawings and Examples by concrete are described in detail the cerebral glioma targeted nano delivery system of IL13R α 2 mediations of the present invention.It needs to be noted, instantiation and accompanying drawing are only in order to illustrate, those of ordinary skill in the art can make various corrections and change to the present invention within the scope of the invention according to explanation herein, and these corrections and change are also included in scope of the present invention.
Accompanying drawing explanation
Fig. 1, the structure of nanoparticle and sign, wherein, (A) transmission electron microscope picture; (B) particle size distribution figure.
Fig. 2, the ILNP that carries DTX suppresses external U87 tumor ball growth figure, wherein, (A) tumor sphere volume-time graph; (B) the shape of tumor figure after drug treatment; DTX concentration 2500ng/mL, Control is administration matched group not, DTX is free Docetaxel group, NP is for carrying a DTX nanoparticle group, ILNP be IL13 peptide modify carry DTX nanoparticle group,
ap<0.05 and matched group comparison;
bp<0.05 and DTX group are relatively;
cp<0.05 and NP group are relatively.
Fig. 3, the live body scattergram of targeted nano granule in lotus glioma nude mouse, wherein, (A) living imaging figure; (B) blood, organ fluorescence imaging figure; (C) brain fluorescence intensity semi-quantitative analysis result figure; (D) organ fluorescence intensity semi-quantitative analysis result figure; (E) cerebral tumor position fluorescence intensity semi-quantitative analysis result figure.
Fig. 4, targeted nano delivery system treatment lotus glioma animal model effect, wherein, (A) is the survival curve of tumor bearing nude mice; (B) (green fluorescence granule represents nucleus apoptosis to TUNEI apoptosis colored graph, and blue markings is nucleus; Experiment divides four groups: normal saline (Saline) group, DTX group, NP group and ILNP group.
The specific embodiment
Preparation and the sign of embodiment 1 IL13 peptide decorated nanometer grain (ILNP)
Adopt emulsifying lyase evaporation to prepare nanoparticle, accurately weigh 1.0mgDTX, 28.0mg methoxyl group-PEG-PCL, 2.0mg carboxyl-PEG-PCL, is dissolved in after 1ml dichloromethane, the sodium cholate that adds 5ml0.6 ﹪, under ice-water bath, ultrasonic 5s, stops 5s, totally 20 times, 37 ℃ revolve steaming 15min removal dichloromethane, and 3500rpm4 ℃ of centrifugal ultrafiltration is concentrated into 1mL.With MES (MES) buffer (pH6.0), cross the desalination of Hitrap desalting column the outer water of displacement, add 4mg1-ethyl-(3-dimethylaminopropyl) phosphinylidyne diimmonium salt hydrochlorate (EDC) and 6mgN-N-Hydroxysuccinimide (NHS) to activate 20 minutes, crossing the desalination of Hitrap desalting column and replacing outer water is 0.01 mol/L phosphate buffer (PBS, pH7.4).Add 20 μ gIL13 peptides, reaction 6h, crosses Sepharose CL-4B post and washes punching, removes unconjugated ILl3 peptide, obtains year DTX nanoparticle (ILNP) that ILl3 peptide is modified.Adopt particle size analyzer to measure particle diameter and the Zete current potential of nanoparticle, after 1% (w/V, pH 7.0) phosphotungstic acid negative staining, transmission electron microscope observing particle shape.As shown in Figure 1, ILNP form rounding, mean diameter 124.5 nm, surperficial Zeta potential is-2.44 mV.
The external glioma cell apoptosis test of embodiment 2
U87 cell is seeded to 6 cm culture plates and cultivates 24 hours, the ILNP that to add containing DTX concentration after cell degree of converging reaches 80% left and right be 500ng/mL cultivates 24 hours.By cell dissociation, adopt apoptosis detection kit (containing annexinV-FITC and propidium iodide 50 μ g/mL) to dye to cell, flow cytometry detects morning, the late period apoptosis rate of cell.It is as shown in table 1 that flow cytometry detects apoptosis result, matched group U87 cell early, late period apoptosis seldom.Compare with matched group, after NP, ILNP, DTX process cell early, late period apoptosis rate all have remarkable increase, the total apoptosis rate of cell significantly increases, wherein, NP, ILNP group process after total apoptosis rate of cell be all significantly higher than DTX group.Table 1 is U87 apoptosis rate (n=3).
Table 1
*p<0.05, compared with the control;
compare with DTX group.
Embodiment 3 vitro inhibition U87 tumor ball growth tests
U87 cell is seeded to 6 well culture plates that have been coated with agarose and cultivates 7 days, make it to be grown to serve as without vascular tumor ball.To add containing DTX concentration be 2500ng/mL, and ILNP cultivates 5 days, measures tumor sphere volume every day, and while take administration, initial tumor sphere volume is with reference to the change in volume of calculating tumor ball.After treatment finishes, tumor ball is fixed to the configuration of surface of scanning electron microscopic observation tumor ball with 2.5% glutaraldehyde.Result as shown in Figure 2 A, the growth of matched group tumor ball is very fast, compares with matched group, and after NP, ILNP, DTX process, the growth of tumor ball is subject to obvious inhibition, the tumor sphere volume of ILNP group, significantly lower than NP and DTX group, shows that ILNP tool is with suppressing preferably tumor ball growth.Scanning electron microscope result also shows, matched group tumor sphere volume is larger, smooth surface, and cellular morphology is complete, clear to be debated.After adopting NP or DTX to process, tumor sphere volume diminishes, and surface is comparatively smooth, but cellular morphology is imperfect, has as seen obvious cell rupture.After adopting ILNP to process, tumor sphere volume is minimum, rough surface, and cellular morphology is imperfect, has obvious cell rupture, can obviously observe coming off of tumor cell.Prompting ILNP can inducing tumor cell apoptosis, suppress the growth of tumor ball.
Set up lotus U87 Brain Glioma Model, with nir dye Dir marking nano grain, by after 10 μ g/kg dosage tail intravenously administrables respectively at 2h, 4h, 8h, 12h, 24h detects nanoparticle in the picked-up at cerebral glioma position, the rear execution thing of administration 24, get each major organs, fluorescence imaging in living imaging instrument, as shown in Fig. 3 result, the fluorescence intensity of the nanoparticle that ILNP modifies at cerebral glioma position is significantly higher than the nanoparticle NP of unmodified, in animal level, confirmed that being modified with of target function molecule I L13 peptide helps nanoparticle and be distributed to cerebral glioma position.
The anti-cerebral glioma pharmacodynamic experiment of embodiment 5
The nude mice of lotus cerebral glioma is divided into four groups at random, is labeled as normal saline group (Saline), free Docetaxel group (DTX), carry Docetaxel nanoparticle group (NP), carry Docetaxel targeted nano granule group (ILNP), plant tumor and within 8 days, press afterwards DTX 10mg/Kg administration, within every 3 days, be administered once, totally four times (the 8th, 11,14,17 days), observe the survival curve of animal, calculate the median survival interval of each treatment group, take matched group as reference, calculate the median survival interval rate elongation of each treatment group.Kind of tumor after 20 days every group get at random 2 animals, put to death and to get brain, dehydration after 10 ﹪ neutral formalins are fixed 24 hours, frozen section after OCT embedding, TUNEL test kit detects apoptosis situation.
As shown in Fig. 4 and table 2, after administration, the death of matched group mice with tumor is the fastest, and after kind tumor, in 30 days all dead (Fig. 4 A), its median survival time is 23.0 days (table 2).Adopt DTX and NP treatment, can significantly delay the death (Fig. 4 A) of mice with tumor, its median survival time is respectively 30.0,35.0 days (table 2).Adopt ILNP treatment can significantly delay the death of mice with tumor, its median survival time is 42.0 days, is significantly higher than DTX and NP group.As shown in Figure 4 B, the dyeing of TUNEL apoptosis shows, the unobservable obvious apoptosis of brain glioblastoma cell of normal saline group, NP and DTX group brain glioblastoma cell have a small amount of apoptosis, and apoptosis of tumor cells degree is significantly higher than NP and DTX group after ILNP treatment, consistent with survival curve result.Above result shows, IL13 peptide can increase specifically DTX and make tumor suppression effect obviously be better than other each groups accumulating of cerebral glioma position.
The median survival time of table 2. mice with tumor (n=6)
ap<0.05 compared with the control,
bp<0.05 compares with DTX group,
cp<0.05 compares with NP group.
SEQUENCE LISTING
<110> Fudan University
<120> targeted nano delivery system for cerebral glioma
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 30
<212> PRT
<213> derives from the small peptide of interleukin-11 3
<400> 1
Val Asp Lys Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln
1 5 10 15
Phe Asn Arg Asn Phe Glu Ser Ile Ile Ile Cys Arg Asp Arg
20 25 30
Claims (8)
1. the targeted nano delivery system for cerebral glioma, it is characterized in that, comprise target function molecule, medicine and nano-carrier, described target function molecule is the small peptide that derives from interleukin-11 3, described medicine is micromolecule antitumor drug, and described nano-carrier is polyethyleneglycol modified liposome, nanoparticle, polymer vesicle, polymer micelle or solid lipid nanoparticle of surface; Described medicine is loaded in nano-carrier with parcel or covalently bound mode bag, and described small peptide is connected with the Polyethylene Glycol on nanoparticle surface by covalently bound mode.
2. by the targeted nano delivery system for cerebral glioma claimed in claim 1, it is characterized in that, described its aminoacid sequence of the small peptide that derives from interleukin-11 3 is:
VDKLLLHLKKLFREGQFNRNFESIIICRDR。
3. by the described targeted nano delivery system for cerebral glioma of claim 1, it is characterized in that, the molecular weight of described Polyethylene Glycol is 1000-20000Da.
4. by the described targeted nano delivery system for cerebral glioma of claim 1, it is characterized in that, the molecular weight of described Polyethylene Glycol is 2000-5000Da.
5. by the targeted nano delivery system for cerebral glioma of claim 1, it is characterized in that, described Polyethylene Glycol is mono methoxy polyethylene glycol or the Polyethylene Glycol that contains other active group.
6. by the targeted nano delivery system for cerebral glioma of claim 5, it is characterized in that, described active group is selected from a kind of in maleimide base, sulfydryl, amido, carboxyl, biotin or Avidin.
7. by the targeted nano delivery system for cerebral glioma of claim 1, it is characterized in that, described targeted nano delivery system particle diameter is 10-300nm.
8. by the targeted nano delivery system for cerebral glioma claimed in claim 1, it is characterized in that, the anti-cerebral glioma medicine of described micromolecule is selected from a kind of in taxanes, Anthraquinones, camptothecin or vinca.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210306978.1A CN103622915B (en) | 2012-08-24 | 2012-08-24 | A kind of targeted nano delivery system for cerebral glioma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210306978.1A CN103622915B (en) | 2012-08-24 | 2012-08-24 | A kind of targeted nano delivery system for cerebral glioma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103622915A true CN103622915A (en) | 2014-03-12 |
| CN103622915B CN103622915B (en) | 2015-10-07 |
Family
ID=50204606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210306978.1A Active CN103622915B (en) | 2012-08-24 | 2012-08-24 | A kind of targeted nano delivery system for cerebral glioma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103622915B (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105497922A (en) * | 2014-09-25 | 2016-04-20 | 复旦大学附属华山医院 | Targeted nano-magnetic resonance contrast agent for brain epileptic foci, preparation and application thereof |
| CN105582539A (en) * | 2014-10-20 | 2016-05-18 | 复旦大学 | Drug delivery system for glioma cell and dependent vessel |
| CN105582540A (en) * | 2014-10-20 | 2016-05-18 | 复旦大学 | Brain glioma targeting drug delivery system by aiming at fatty acid-binding protein acceptor |
| CN106619571A (en) * | 2017-01-03 | 2017-05-10 | 西南交通大学 | Polymer nanocarrier capable of promoting endocytosis and cell nucleus targeting and preparation method of polymer nanocarrier |
| CN108126189A (en) * | 2018-02-12 | 2018-06-08 | 中国药科大学 | It is classified nano combined carrier delivery system and its application of assembling |
| CN110354096A (en) * | 2019-07-03 | 2019-10-22 | 中国人民解放军第四军医大学 | Have both the brain targeting drug delivery system for improving drug resistance glioma microenvironment and reversing drug resistance |
| WO2019237884A1 (en) * | 2018-06-14 | 2019-12-19 | 复旦大学 | AMYLOID β SHORT PEPTIDE MEDIATED BRAIN TARGETED DELIVERY SYSTEM, PREPARATION METHOD THEREFOR AND USE THEREOF |
| CN113384707A (en) * | 2021-07-16 | 2021-09-14 | 高州市人民医院 | Preparation method of novel nano preparation capable of treating brain glioma |
| CN113480603A (en) * | 2021-07-13 | 2021-10-08 | 四川大学 | Specific short peptide targeting glioma cells, coding gene and application thereof |
| CN116869968A (en) * | 2023-09-07 | 2023-10-13 | 四川大学 | Nanoparticulate targeting brain and brain glioma, and synthesis method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009045579A2 (en) * | 2007-06-14 | 2009-04-09 | The Regents Of The University Of California | Multimodal imaging probes for in vivo targeted and non-targeted imaging and therapeutics |
| CN101588816A (en) * | 2006-10-19 | 2009-11-25 | 默克制药公司 | High affinity antibody antagonists of interleukin-13 receptor alpha 1 |
-
2012
- 2012-08-24 CN CN201210306978.1A patent/CN103622915B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101588816A (en) * | 2006-10-19 | 2009-11-25 | 默克制药公司 | High affinity antibody antagonists of interleukin-13 receptor alpha 1 |
| WO2009045579A2 (en) * | 2007-06-14 | 2009-04-09 | The Regents Of The University Of California | Multimodal imaging probes for in vivo targeted and non-targeted imaging and therapeutics |
Non-Patent Citations (2)
| Title |
|---|
| 俞文桥等: "人脑胶质瘤特异抗原肽白介素13α2受体的原核表达", 《中国肿瘤临床》, vol. 38, no. 9, 31 December 2011 (2011-12-31), pages 488 - 491 * |
| 张振宇: "纳米载体系统治疗恶性胶质瘤研究进展", 《国际精神病学神经外科学杂志》, vol. 38, no. 3, 31 December 2011 (2011-12-31) * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105497922A (en) * | 2014-09-25 | 2016-04-20 | 复旦大学附属华山医院 | Targeted nano-magnetic resonance contrast agent for brain epileptic foci, preparation and application thereof |
| CN105497922B (en) * | 2014-09-25 | 2018-11-16 | 复旦大学附属华山医院 | For the targeted nano mr contrast agent of brain epileptogenic focus and its preparation and application |
| CN105582539A (en) * | 2014-10-20 | 2016-05-18 | 复旦大学 | Drug delivery system for glioma cell and dependent vessel |
| CN105582540A (en) * | 2014-10-20 | 2016-05-18 | 复旦大学 | Brain glioma targeting drug delivery system by aiming at fatty acid-binding protein acceptor |
| CN105582539B (en) * | 2014-10-20 | 2019-01-11 | 复旦大学 | It is a kind of for glioma cell and its rely on blood vessel drug delivery system |
| CN106619571A (en) * | 2017-01-03 | 2017-05-10 | 西南交通大学 | Polymer nanocarrier capable of promoting endocytosis and cell nucleus targeting and preparation method of polymer nanocarrier |
| CN108126189A (en) * | 2018-02-12 | 2018-06-08 | 中国药科大学 | It is classified nano combined carrier delivery system and its application of assembling |
| CN108126189B (en) * | 2018-02-12 | 2021-03-02 | 中国药科大学 | Nano composite carrier drug delivery system assembled in grading manner and application thereof |
| WO2019237884A1 (en) * | 2018-06-14 | 2019-12-19 | 复旦大学 | AMYLOID β SHORT PEPTIDE MEDIATED BRAIN TARGETED DELIVERY SYSTEM, PREPARATION METHOD THEREFOR AND USE THEREOF |
| CN110604821A (en) * | 2018-06-14 | 2019-12-24 | 复旦大学 | Brain targeting delivery system mediated by amyloid beta short peptide |
| CN110354096A (en) * | 2019-07-03 | 2019-10-22 | 中国人民解放军第四军医大学 | Have both the brain targeting drug delivery system for improving drug resistance glioma microenvironment and reversing drug resistance |
| CN113480603A (en) * | 2021-07-13 | 2021-10-08 | 四川大学 | Specific short peptide targeting glioma cells, coding gene and application thereof |
| CN113480603B (en) * | 2021-07-13 | 2022-03-01 | 四川大学 | Specific short peptide targeting glioma cells, coding gene and application thereof |
| CN113384707A (en) * | 2021-07-16 | 2021-09-14 | 高州市人民医院 | Preparation method of novel nano preparation capable of treating brain glioma |
| CN116869968A (en) * | 2023-09-07 | 2023-10-13 | 四川大学 | Nanoparticulate targeting brain and brain glioma, and synthesis method and application thereof |
| CN116869968B (en) * | 2023-09-07 | 2023-11-24 | 四川大学 | Nanoparticulate targeting brain and brain glioma, and synthesis method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103622915B (en) | 2015-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103622915B (en) | A kind of targeted nano delivery system for cerebral glioma | |
| Zhao et al. | Enhancement of radiosensitization by silver nanoparticles functionalized with polyethylene glycol and aptamer As1411 for glioma irradiation therapy | |
| Feng et al. | Self-assembly of gold nanoparticles shows microenvironment-mediated dynamic switching and enhanced brain tumor targeting | |
| Sun et al. | Transferrin receptor-targeted PEG-PLA polymeric micelles for chemotherapy against glioblastoma multiforme | |
| Chen et al. | Transferrin-modified liposome promotes α-mangostin to penetrate the blood–brain barrier | |
| Luo et al. | Precise glioblastoma targeting by AS1411 aptamer-functionalized poly (l-γ-glutamylglutamine)–paclitaxel nanoconjugates | |
| Han et al. | Enzyme-sensitive gemcitabine conjugated albumin nanoparticles as a versatile theranostic nanoplatform for pancreatic cancer treatment | |
| Huang et al. | Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration | |
| Han et al. | Hypericin-functionalized graphene oxide for enhanced mitochondria-targeting and synergistic anticancer effect | |
| US9371364B2 (en) | Dual-targeted therapeutic peptide for nasopharyngeal carcinoma, nanoparticles carrying same and uses thereof | |
| CN103169982B (en) | Biological active peptide modified nano-silver and preparation method and applications thereof | |
| Shao et al. | A smart multifunctional nanoparticle for enhanced near-infrared image-guided photothermal therapy against gastric cancer | |
| Xu et al. | Hyaluronic acid coated liposomes Co-delivery of natural cyclic peptide RA-XII and mitochondrial targeted photosensitizer for highly selective precise combined treatment of colon cancer | |
| WO2019080504A1 (en) | Cell penetrating peptide and cell penetrating peptide complex, and application thereof | |
| Zou et al. | Selenium nanoparticles coated with pH responsive silk fibroin complex for fingolimod release and enhanced targeting in thyroid cancer | |
| Ma et al. | tLyP-1 peptide functionalized human H chain ferritin for targeted delivery of paclitaxel | |
| Song et al. | Erythrocyte-biomimetic nanosystems to improve antitumor effects of paclitaxel on epithelial cancers | |
| Liang et al. | A nanosystem of amphiphilic oligopeptide-drug conjugate actualizing both αvβ3 targeting and reduction-triggered release for maytansinoid | |
| Chen et al. | RETRACTED ARTICLE: The therapeutic effect of methotrexate-conjugated Pluronic-based polymeric micelles on the folate receptor-rich tumors treatment | |
| CN107157950B (en) | Albumin nanoparticles and preparation method and application thereof | |
| Yang et al. | Subcellular co-delivery of two different site-oriented payloads for tumor therapy | |
| Nagesetti et al. | Polyethylene glycol modified ORMOSIL theranostic nanoparticles for triggered doxorubicin release and deep drug delivery into ovarian cancer spheroids | |
| CN106215191A (en) | A kind of cerebral glioma targeting drug delivery system and its production and use | |
| Wang et al. | Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration | |
| Yu et al. | Camouflaged Virus‐Like‐Nanocarrier with a Transformable Rough Surface for Boosting Drug Delivery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | 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 |