Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Yaming Gu,Yizhen Guo,Changyong Wang,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
It is a promising way to treat the multi drug resistance (MDR) of tumor cells in both of drug and gene methods. A polyamidoamne dendrimer functionalized graphene oxide (GO-PAMAM) was designed, which could load doxorubicin (DOX) and MMP-9 shRNA plasmid at the same time in order to achieve effective treatment to breast cancer. GO-PAMAM has a high loading capacity to DOX and pH-controlled DOX release. Besides, it has efficient gene transfer ability, the transfection efficiency is significantly better than PEI-25k in the presence of serum, and it can significantly inhibit the expression of MMP-9 protein in MCF-7 cells. The effect of DOX and MMP-9 shRNA plasmid co-delivery was more significant than that of the single drug. Moreover, GO-PAMAM exhibited lower cytotoxicity compared to PEI-25k in CCK-8 assays, and also showed a good biocompatibility in vivo . Therefore, GO-PAMAM will have broad prospects for drug and gene co-delivery.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Tao Liu,Xidong Wu,Shaohua Chen,Peina Wu,Hong Han,Hongbin Zhang,Junzheng Li,Guanxue Li,Siyi Zhang
To obtain a high-efficiency drug and gene co-delivery system to HNE-1 tumor therapy, a polymeric prodrug (PAAs-MTX) with chemotherapeutic sensibilization was synthesized consisting of a GSH-response hyperbranched poly(amido amine) (PAAs) and an antitumor drug of methotrexate (MTX). Then, the targeting molecule to HNE-1 cells, transferrin (Tf), was conjugated to form the Tf-PAAs-MTX. This polymeric prodrug could deliver MMP-9 shRNA plasmid (pMMP-9) again to form the drug and gene co-delivery system of Tf-PAAs-MTX/pMMP-9. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency to HNE-1 cells. Besides that, Tf-PAAs-MTX also showed the chemotherapeutic sensibilization effect, the formulation containing PAAs segments showed much higher cytotoxicity than that of free MTX. Benefiting from the sensibilization effect and MTX/pMMP-9 co-delivery strategy, this Tf-PAAs-MTX/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. Moreover, its biocompatibility, especially the blood compatibility was analyzed. This polymeric prodrug provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization and targeting into one single platform, which showed a promising application in nasopharyngeal carcinoma therapy.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Qiao Tang,Xin Ma,Yi Zhang,Xiang Cai,Wei Xue,Dong Ma
Polymeric prodrugs are of immense interest as anticancer drug-delivery system owing to their superior drug stability during circulation and satisfactory drug loading capacity. However, they are usually less effective than free drugs due to imperfect degradable characteristics or active sites blockage. A polymeric prodrug (HPAA-MTX) with chemotherapeutic self-sensibilization effect consisting of glutathione (GSH)-triggered hyperbranched poly(amido amine) (HPAA) and methotrexate (MTX) was designed and synthesized in this work. This prodrug not only showed better inhibition effect on the tumor cells proliferation compared with free MTX , but also displayed selective sensibilization to tumor cells rather than normal cells. Meanwhile, HPAA-MTX was also explored as a MMP-9 shRNA plasmid delivery vector due to their rich amino group of HPAA, accompanying with MTX for simultaneous inhibiting tumor cells proliferation and migration. As expected, HPAA-MTX possessed excellent gene delivery capacity with significant down-regulation expression of MMP-9 protein and further inhibition of MCF-7 cells migration. Benefiting from the self-sensibilization effect and MTX/MMP-9 co-delivery strategy, this HPAA-MTX/MMP-9 co-delivery system exhibited significantly improved therapeutic efficacy to breast cancer in a combined manner which was confirmed through in vitro and in vivo assays. The strategy established in this study provided a facile “all-in-one” platform to integrate the drug/gene co-delivery strategy and self-sensibilization effect into one single nanocomposite for potential cancer treatment. Statement of significance A cationic polymeric prodrug with chemotherapeutic self-sensibilization effect was designed and showed better inhibition effect on tumor cells proliferation compared with its free drug, as well displayed the selective sensibilization effect to tumor cells rather than normal cells. Moreover, the prodrug could also deliver MMP-9 shRNA plasmid for a combined therapy. As expected, the prodrug possessed excellent gene delivery capacity with significant down-regulation expression of MMP-9 protein and further inhibition of MCF-7 cells migration. Benefiting from the self-sensibilization effect and the drug/gene co-delivery strategy, this prodrug exhibited significantly improved therapeutic efficacy to breast cancer in a combined manner.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2016
·
IF 6.008
Qianming Lin,Yumeng Yang,Qian Hu,Zhong Guo,Tao Liu,Jiake Xu,Jianping Wu,Thomas Brett Kirk,Dong Ma,Wei Xue
Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly( l -lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system , this supramolecular hydrogel is a promising candidate for long-term gene therapy. Statement of Significance To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly( l -lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth inhibition meanwhile keep good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate in long-term gene therapy and tissue engineering.
研究领域:
生物材料学
·
基因治疗
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Yanan Kang,Lu Lu,Jinshuai Lan,Yue Ding,Jing Yang,Yong Zhang,Yuan Zhao,Tong Zhang,Rodney J.Y. Ho
A novel redox-sensitive system for co-delivering hydrophobic drugs and hydrophilic siRNA or shRNA was developed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs) through amide bonds, which is called GA-conjugated PAAs (PAG). PAG can self-assemble into micelles as amphiphilic block copolymers , which exhibits an excellent loading ability for the co-delivery of docetaxel (DTX) and MMP-9 shRNA with adjustable dosing ratios. In addition, confocal microscopy , flow cytometry and in vitro transfection analyses demonstrated more efficient cellular internalization of DTX and MMP-9 shRNA after incubation with PAG/DTX- MMP-9 shRNA micelles (PAG/DTX-shRNA) than with free drugs. Unlike traditional amphiphilic copolymer micelles, GA conjugated in PAG possesses an intrinsic anticancer efficacy. The presence of disulfide bonds in PAAs enables rapid disassembly of PAG micelles in response to reducing agents, inducing the release of loaded drugs (DTX, GA and MMP-9 shRNA). In vitro cellular assays revealed that PAG/DTX-shRNA micelles inhibited MCF-7 cell proliferation more efficiently than the single drug or single drug-loaded micelles. In vivo biodistribution and anti-tumor effect studies using an MCF-7 breast cancer xenograft mouse model have indicated that PAG/DTX-shRNA micelles can enhance drug accumulation compared with the free drug, thereby sustaining the therapeutic effect on tumors. Additionally, PAG/DTX-shRNA micelles displayed a greater anti-tumor efficacy than Taxotere® and PAG-shRNA micelles. These results suggest that the redox-sensitive PAG platform is a promising co-delivery system for combining drugs and gene therapy for the treatment of cancer. Statement of Significance The PAG micelles were designed by conjugating gambogic acid (GA) with poly(amido amine)s (PAAs), which would serve dual purposes as both gene and drugs co-delivery carrier and an anti-tumor prodrug. Unlike traditional amphiphilic micelles, GA conjugated in PAG could exert its intrinsic efficacy and provide synergistic antiproliferative effects with docetaxel (DTX) on MCF-7 cells. Disulfide bonds in PAG enables a rapid disassembly of PAG micelles in response to reducing agents and to release all loaded drugs (DTX, GA and MMP-9 shRNA) at tumor sites. PAG/DTX-shRNA micelles displayed greater anti-tumor efficacy than that of Taxotere®, indicating the design concept for PAG works well. And the strategy for PAG could be used to develop a series of similar co-delivery systems through conjugations of other small-molecule drugs with PAAs, such as doxorubicin , methotrexate and other drugs with carboxy groups in their structure.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2016
·
IF 7.145
Yi Zhang,Junkun Duan,Lingguang Cai,Dong Ma,Wei Xue
For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.
研究领域:
生物化学
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2019
·
IF 10.159
Siming Yu,Rong Wen,Haiyang Wang,Yongchao Zha,Lin Qiu,Bo Li,Wei Xue,Dong Ma
Au nanoclusters (Au NCs) are materials that hold great promise in biomedical applications due to their improved photophysical properties. However, the current nonthiolate polymer-based self-assembly methods for preparing Au NCs face drawbacks of usage of environmentally unfriendly reducing reagents or nonbiocompatible polymers, which largely hamper their more extensive biomedical use. In this work, biocompatible chitosan-graft-poly(l-lysine) (CPL) dendrons are designed and synthesized based on a simple azide–alkyne cyclization reaction for facile preparation of Au@CPL NCs in one step. The obtained Au@CPL NCs exhibited enhanced computer tomography imaging property as compared with clinically used iohexol (Omnipaque) and displayed high delivery efficiency for matrix metalloproteinase-9 plasmid shRNA (pMMP-9). After surface functionalization by cyclic arginine-glycine-aspartic (Arg-Gly-Asp, RGD), a peptide that specifically targets αvβ3 integrin overexpressed by cancer cells, the resultant Au@CPL-RGD/pMMP-9 complex can precisely and efficiently inhibit tumor growth both in vitro and in vivo. Our work provides a novel strategy to fabricate Au NCs with enhanced biorelevant properties for more efficient cancer diagnosis and therapy.
研究领域:
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 26
·4314-4325
·
IF 4.776
Tao Liu,Shaohua Chen,Siyi Zhang,Xidong Wu,Peina Wu,Beiping Miao,Xiang Cai
Transferrin-functionalized chitosan-graft-poly(L-lysine) dendrons (CS–PLLD–Tf) were synthesized in this work and then used to deliver the MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS–PLLD–Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS–PLLD–Tf showed much higher gene transfection efficiency than PEI-25k and CS–PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition of the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS–PLLD–Tf delivered the MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with the PBS control group. Moreover, CS–PLLD–Tf displayed higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy of tumors.
研究领域:
癌症研究
·
基因治疗
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Tao Liu,Jingzhen Li,Xidong Wu,Siyi Zhang,Zhongming Lu,Guanxue Li,Junzheng Li,Shaohua Chen
A drug and gene co-delivery system with chemotherapeutic sensibilization was prepared and used for nasopharyngeal carcinoma therapy. For this purpose, the graphene oxide (GO) was conjugated with the redox hyperbranched poly(amido amine) (HPAA) and then the targeting molecule, transferrin (Tf), was also conjugated. The obtained Tf-HPAA-GO could co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid (pMMP-9) effectively and showed the targeting effect to HNE-1 cells. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency. Besides that, Tf-HPAA-GO/DOC also showed the chemotherapeutic sensibilization effect, the formulation containing HPAA segments showed much higher cytotoxicity than free DOC. Benefiting from the sensibilization effect and DOC/pMMP-9 co-delivery strategy, this Tf-HPAA-GO/DOC/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. This strategy provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization, and targeting into one single platform, which showed a promising application in cancer therapy.
研究领域:
癌症治疗
·
药学
·
生物材料
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）