JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2017
·
IF 1.194
Wei Wang,Biyun Zhao,Xiangyang Meng,Pan She,Pantian Zhang,Yi Cao,Xuefei Zhang
The traditional chemotherapy using single agent may suffer from serious drawbacks, particularly dose-limiting toxicity and relatively low antitumor efficacy, which can lead to failure of chemotherapy. Co-delivery of two or more therapeutic drugs in nanotechnology is a potential strategy to generate synergistic anticancer effects and reduce individual drug-related toxicity, but explosive release of each drug from multi-drug loaded nanoparticles has been a distinct obstacle. In this study, a novel amphiphilic and biodegradable triblock copolymer , named MPEG-b-norbornene functional PLA-b-P(α-BrCL), was constructed to covalently conjugate dual anticancer drugs , i.e., doxorubicin (DOX) and paclitaxel (PTX). The resultant P-PTX-DOX prodrugs were confirmed by 1 H NMR and HPLC. By adjusting the length of PLA and PCL, it was shown that this polymer could carry relatively sufficient amount of both drugs (12.1 wt% of PTX and 15.8 wt% of DOX, respectively). Moreover, the drug release profile of P-PTX-DOX in vitro was also analyzed, which showed the desired drug release in a sustained manner. Cytotoxicity study indicated synergistic effects of P-PTX-DOX self-assembled micelles in suppression of proliferation of A549 cancer cells. In summary, a novel polyester-based copolymer was developed to covalently conjugate dual-drug, which exhibited controlled drug release behavior and synergistic anti-cancer efficacy in vitro.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Weifeng Lin,Yueying He,Juan Zhang,Longgang Wang,Zhen Wang,Fangqin Ji,Shengfu Chen
Both blood stability and intelligent-responsiveness after reaching the drug-targeting site are very important features to make desirable nano-drug vehicles (NDVs). Here, a highly nonfouling cross-linked micelle based on a copolymer composed of carboxybetaine methacrylate (CBMA) as hydrophilic segment and 2-(methacryloyloxy)ethyl lipoate (MAEL) as hydrophobic and cross-linked segment is reported. Furthermore, a simple method to evaluate the hemocompatibility of NDVs through examining the activation of a blood-clotting protein (fibrinogen) was introduced. The micelles can encapsulate anticancer drug doxorubicin (DOX) conveniently and release DOX quickly in response to an intracellular reductive environment. With the advantages of excellent stability in fibrinogen (1 mg/mL) PBS solution and 50% fetal bovine serum (FBS), and accelerated intracellular drug release, the biocompatible zwitterionic micelles stabilized by reversible cross-linkage might be a promising drug carrier for cancer chemotherapy.
研究领域:
生物材料学
·
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
POLYMER SCIENCE SERIES A
·
2021
·Vol. 63
·期 6
·769-778
·
IF 1.206
Yu Lili,Yao Lin,Yang Kuan,Fei Wenling,Chen Qingqing,Qin Lan,Liu Shaojing,Zou Zengqiang,Qin Bei
Abstract The surface cRGD modified polymeric (PMMA- b -PPEGMA-RGD) micelles were constructed by a combination of two-step atom transfer radical polymerization (ATRP), azide reaction, click reaction, deprotection, self-assembly of amphiphilic polymers, and addition reaction. The self-assembled DOX-loaded micelles had spherical morphology. The average size of DOX-loaded micelles measured by scanning electron microscopy (SEM) and dynamic light scattering (DLS) was less than 200 nm. According to the enhanced permeability and retention (EPR) effect of solid tumors, the micelles should have the passive targeting of tumor tissues. The introduction of cRGD on the micelles surface can not only achieve the active targeting of drug carriers to tumor tissues, but also form the network hydrogen bond between the PEG unit at the hydrophilic end of the micelles and the guanidine group in RGD, to improve the uniformity of the particle size distribution and the stability of drug loading, and also achieve the slow release of drugs. The cytotoxicity of DOX-loaded micelles on SGC7901 cells in vitro indicated that PMMA- b -PPEGMA-RGD micelles could provide the same or more remarkable antitumor activity (at low dose) as DOX. The results showed that PMMA- b -PPEGMA-RGD micelles might have great potential applications in the delivery of hydrophobic anticancer drugs.
研究领域:
药剂学
·
聚合物化学
·
药物递送系统
·
癌症研究
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Qi-Ming Wang,Zhonggao Gao,Shan Liu,Bo Fan,Lin Kang,Wei Huang,Mingji Jin
The bioactive polymer poly( l -glutamic acid) n - b -poly( d , l -lactic acid) m was synthesized and used to form doxorubicin-loaded hybrid polymeric micelles to treat melanoma. These polymers exhibited pH-responsive changes in conformation, which controlled the diverse functionalities of the micelles. During circulation, poly( l -glutamic acid) n - b -poly( d , l -lactic acid) m protected Tat peptides on the micelles from proteolysis . Under tumor-acidic conditions, polymers with shorter poly( l -glutamic acid) blocks underwent a conformational change to form channels that accelerated the release of doxorubicin . The conformational change also exposed the Tat peptides to tumor cells, thereby promoting cellular internalization of the micelles. Enhanced cellular uptake of the micelles induced significant apoptosis of A375 melanoma cells in tumor-acidic conditions. In vivo studies demonstrated that the micelles with shorter poly( l -glutamic acid) blocks could effectively accumulate in tumor tissues, suppress tumor growth and help maintain the body weight of tumor-bearing mice. However, micelles with longer poly( l -glutamic acid) blocks did not undergo a conformational change under acidic conditions and performed poorly in both in vitro and in vivo evaluations. Our work provides a strategy for applying bioactive polymers to the rational construction of pH-responsive delivery systems for solid tumors and lends insight into possible conformational effects on the bioactivity of drug carriers.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2014
·
IF 5.788
Yang Li,Junjie Li,Biao Chen,Qixian Chen,Guoying Zhang,Shiyong Liu,Zhishen Ge
Adequate retention in blood circulation is a prerequisite for construction of gene delivery carriers for systemic applications. The stability of gene carriers in the bloodstream requires them to effectively resist protein adsorption and maintain small size in the bloodstream avoiding dissociation, aggregation, and nuclease digestion under salty and proteinous medium. Herein, a mixture of two block catiomers consisting of the same cationic block, poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PAsp(DET)), but varying shell-forming blocks, poly[2-(2-methoxyethoxy) ethyl methacrylate] (PMEO2MA), and poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA), was used to complex with plasmid DNA (pDNA) to fabricate polyplex micelles with mixed shells (MPMs) at 20 °C. The thermoresponsive property of PMEO2MA allows distinct phase transition from hydrophilic to hydrophobic by increasing incubation temperature from 20 to 37 °C, which results in a distinct heterogeneous corona containing hydrophilic and hydrophobic regions at the surface of the MPMs. Subsequent study verified that this transition promoted further condensation of pDNA, thereby giving rise to improved complex and colloidal stability. The proposed system has shown remarkable stability in salty and proteinous solution and superior tolerance to nuclease degradation. As compared with polyplex micelles formed from single POEGMA-b-PAsp(DET) block copolymer, in vivo circulation experiments in the bloodstream further confirmed that the retention time of MPMs was prolonged significantly. Moreover, the proposed system exhibited remarkably high cell transfection activity especially at low N/P ratios and negligible cytotoxicity and thus portends promising utility for systemic gene therapy applications.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2018
·Vol. 56
·期 13
·1383-1394
·
IF 2.588
Huiru Yang,Xuezhi Zhao,Xiaolong Zhang,Liwei Ma,Baoyan Wang,Hua Wei
Dendritic polymers-based unimolecular micelles with enhanced stability are attractive carriers. However, the preparation of dendrimers or dendrons with higher generation remains substantially synthetic challenge due to the increased steric hindrance, multistep and tedious preparation, and low yields. The adoption of Boltorn H40, a commercially available dendritic polymer of Boltorn family containing multiple hydroxyl groups with various functionalities as a dendrimer-based starting core template for the generation of hyperbranched polymers, offers a straightforward solution to address this problem. To develop universal strategies toward H40-based amphiphilic block copolymers, the “grafting from” and “grafting to” approaches were both applied in this study. The reduction-insensitive block copolymers, H40- b -poly(ɛ-caprolactone)- b -poly(oligo(ethylene glycol) monomethyl ether methacrylate) (H40- b -PCL- b -POEGMA), were synthesized by “grafting from” including sequential ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The core structure and the polymer composition of the nonreducible amphiphilic hyperbranched block copolymers were optimized toward better properties and performance for drug delivery applications, and H40-PCL 15 - b -POEGMA 23 was screened as the best polymer construct relative to H20-PCL 15 - b -POEGMA 23 and H40-PCL 15 - b -POEGMA 32 in terms of micelle stability and drug loading capacity. Therefore, the reducible H40- b -PCL-SS-POEGMA with an identical core and polymer composition to that of H40-PCL 15 - b -POEGMA 23 was further prepared by “grafting to” using click coupling between H40-PCL-azide and P(OEGMA)-alkyne. The delivery efficacy evaluated by an in vitro cytotoxicity study revealed that the resulting DOX-loaded reducible micelles of H40-PCL 15 -SS-POEGMA 23 produced greater cytotoxicity in cancer cells than in normal cells and macrophages, therefore, are promising carriers for anticancer drug delivery. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56 , 1383–1394
研究领域:
聚合物化学
·
药物递送系统
·
材料科学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Nanoscale
·
2015
·Vol. 8
·期 1
·283-291
·
IF 7.394
Haijie Han,Haibo Wang,Yangjun Chen,Zuhong Li,Yin Wang,Qiao Jin,Jian Ji
A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and “click” reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.
研究领域:
药学
·
癌症治疗
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2017
·
IF 8.766
Qu Jin,Yu Cai,Sihan Li,Haoran Liu,Xingyu Zhou,Chunqiang Lu,Xihui Gao,Jun Qian,Jun Zhang,Shenghong Ju,Cong Li
Thrombolysis has been a standard treatment for ischemic stroke. However, only 2-7% patients benefit from it because the thrombolytic agent has to be injected within 4.5 h after the onset of symptoms to avoid the increasing risk of intracerebral hemorrhage. As the only clinically approved neuroprotective drug, edaravone (EDV) rescues ischemic brain tissues by eradicating over-produced reactive oxygen species (ROS) without the limitation of therapeutic time-window. However, EDV's short circulation half-life and inadequate cerebral uptake attenuate its therapeutic efficacy. Here we developed an EDV-encapsulated agonistic micelle (EDV-AM) to specifically deliver EDV into brain ischemia by actively tuning blood-brain barrier (BBB) permeability. The EDV-AM actively up-regulated endothelial monolayer permeability in vitro . HPLC studies showed that EDV-AM delivered more EDV into brain ischemia than free EDV after intravenous injection. Magnetic resonance imaging also demonstrated that EDV-AM more rapidly salvaged ischemic tissue than free EDV. Diffusion tensor imaging indicated the highest efficiency of EDV-AM in accelerating axonal remodeling in the ipsilesional white matter and improving functional behaviors of ischemic stroke models. The agonistic micelle holds promise to improve the therapeutic efficiency of ischemic stroke patients who miss the thrombolytic treatment.
研究领域:
药理学
·
神经科学
·
生物医学工程
·
中风治疗
✓ 已验证
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2017
·
IF 5.246
Yang Pan,Xiaoting Ren,Shuang Wang,Xin Li,Xianglin Luo,Zongning Yin
To alleviate the hemorrhagic side effect of thrombolysis therapy, a thrombus targeted drug delivery system based on the specific affinity of Annexin V to phosphatidylserine exposed on the membrane surface of activated platelet was developed. The amphiphilic and biodegradable biomaterial, polycaprolactone-block-poly(2-(dimethylamino)ethyl methacrylate)-block-poly(2-hydroxyethyl methacrylate) (PCL-b-PDMAEMA-b-PHEMA (PCDH)) triblock polymer, was synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) to use as the nanocarriers of thrombolytic drug. In order to conjugate Annexin V to the polymer, PCDH was modified by succinic anhydride via ring-opening reaction to introduce the carboxyl group (PCDH-COOH). After preparation of PCDH/PCDH-COOH (9/1, m/m) mixed micelles, Annexin V was coupled with the micelles using carbodiimide chemistry. The blood clot lysis assay in vitro confirmed that lumbrokinase-loaded targeted micelles (LKTM) had stronger thrombolysis potency than free lumbrokinase (LK) and LK-loaded nontargeted micelles (LKM, P < 0.05). In vivo thrombolytic assay, multispectral, optoacoustic tomography (MSOT) was used to assess the target ability of LKTM. The results of MSOT images indicated the fluorescence intensity of the LKTM group located in the blood clot position were significantly stronger than the LKM group. A 5 mm of carotid artery containing blood clot was cut out 24 h later after administration to assess the degree of thrombolysis. The results of thrombolytic assay in vivo were consistent with the assay in vitro, which the differences between LK, LKM, and LKTM groups were both statistically significant. All the results of thrombolysis assays above proved that the capacity of thrombolysis in the LKTM group was optimal. It suggested that Annexin V-conjugated micelles will be a potential drug delivery system for targeted thrombolysis.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
药物递送
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Yunchun Zhao,Caihong Zheng,Li Zhang,Yue Chen,Yiqing Ye,Mengdan Zhao
Biodegradable and biocompatible poly( d,l -lactic- co -glycolic acid) (PLGA)was conjugated to the 5′-thiol end of signal transducer and activator of transcription 3 (STAT3) small interfering RNA (STAT3–siRNA) via a disulfide bond. In aqueous environments, these siRNA–PLGA conjugates can spontaneously form core/shell type spherical micelles with a particle size of about 200 nm. A biodegradable, low molecular weight cationic polymer, chitosan oligosaccharide (CSO), was added to the siRNA–PLGA micelles at different nitrogen to phosphate (N/P) ratios to form stable, spherical siRNA–PLGA/CSO micelles with sizes of 150–180 nm. The siRNA–PLGA/CSO micelles were produced via ionic complexation between negatively charged siRNA and positively charged CSO on the outer shell of the micelles. The siRNA–PLGA/CSO micelles exhibited superior cellular uptake and STAT3 gene silencing efficiency in SKOV3 ovarian cancer cells when compared with siRNA/CSO complexes at the same N/P ratios with no significant differences with lipofectamine 2000. Furthermore, the siRNA–PLGA/CSO micelles showed that the efficiencies of cellular uptake and STAT3 gene silencing gradually increased with increasing N/P ratios. The siRNA–PLGA/CSO micelles also inhibited the growth of SKOV3 cells, as well as, promoted apoptosis of the cells. These results indicate that siRNA–PLGA/CSO micelles can be utilized as a novel and efficient siRNA carrier to treat a variety of diseases.
研究领域:
癌症研究
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 46
·23756-23767
·
IF 6.895
Chao Teng,Beiyuan Zhang,Zhongyue Yuan,Zheng Kuang,Zhuodong Chai,Lianjie Ren,Chao Qin,Lei Yang,Xiaopeng Han,Lifang Yin
Cancer-associated fibroblasts (CAFs) are the majority cell population of tumor stroma, and they not only play important roles in tumor growth and metastasis, but they also form a protective physical barrier for cancer cells. Herein, we designed a fibroblast activation protein-α (FAP-α)-adaptive polymeric micelle based on hyaluronic acid and curcumin conjugates. The polymeric micelle is composed of a CD44-targeting shell and a FAP-α-cleavable polyethylene glycol (PEG) coating. When FAP-α is encountered on the surface of CAFs in the tumor microenvironment, the PEG layer is released, hyaluronic acid is recovered on the surface of nanoparticles, and the nanoparticles effectively inhibit the growth of tumor cells and CAFs through CD44-mediated endocytosis. The FAP-α-adaptive polymeric micelle exhibited potent anti-cancer efficacy by enhancing CAF apoptosis and reducing collagen in tumor tissues. Collectively, FAP-α-adaptive nanoparticles may be a promising method for antitumor anticancer treatments via reprogramming of stroma fibrosis.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2026
·
IF 10.4
Xiangrong Dai,Yi Liao,Rong Chen,Xuanxiang Jin,Jiajia Dong,Ying Tan,Xuru Jin
Nebulized inhalation represents an attractive approach for pulmonary drug delivery due to its non-invasiveness and direct lung targeting capability. However, the effectiveness of conventional inhaled formulations is limited by their inability to simultaneously evade mucociliary clearance and macrophage phagocytosis, leading to suboptimal lung retention and low bioavailability. To address these challenges, a series of ultra-small zwitterionic "camouflage" micelles, Distearoylphosphatidylethanolamine (DSPE)-block-poly ( N -methacryloyloxyethyl- N, N -dimethylammonium-α-N-methylcarboxybetaine) (CB) (D-PCB n ), were developed to synergize biomimetic targeting with enhanced mucosal penetration. The micelles feature a DSPE-based core structurally modeled after dipalmitoylphosphatidylcholine (DPPC), a key pulmonary surfactant lipid, enabling biomimetic alveolar targeting. Simultaneously, a carboxybetaine-derived corona facilitates robust hydration-mediated surface lubrication for efficient mucus penetration. Among the series, the optimized D-PCB 30 variant exhibited superior mucus-permeating capacity, enhanced pulmonary deposition, and high encapsulation efficiency for dexamethasone. In vivo evaluation in a murine model following aerosol administration demonstrated significantly improved lung accumulation, extended residence time, reduced systemic distribution, and enhanced anti-inflammatory efficacy. Transcriptomic analysis further indicated modulation of critical inflammatory pathways and reprogramming of macrophage polarization (M1 to M2 phenotype), corroborating the therapeutic benefits achieved through enhanced barrier penetration. These results demonstrate the potential of D-PCB n micelles as a promising inhalable nanoplatform for targeted treatment of lung diseases. Statement of Significance Delivering therapeutics to injured lungs is hampered by mucus barriers, rapid clearance, and immune sequestration. Here, we describe ultra-small, biomimetic zwitterionic micelles D-PCBMA n (D-PCB 30 ) that combine a DPPC-mimetic DSPE core with a carboxybetaine corona to create a “camouflage-and-lubricate” nanoplatform. D-PCB 30 exhibits a low critical micelle concentration (CMC), high drug loading, and stability upon nebulization, enabling deep mucus penetration, reduced macrophage uptake, and sustained pulmonary residence. When loaded with dexamethasone (DEX) and delivered by nebulization, D-PCB 30 increases local drug deposition while reducing systemic exposure, resulting in potent attenuation of LPS-driven inflammation, preservation of alveolar architecture, and diminished fibrotic remodeling. Mechanistically, transcriptomic profiling reveals suppression of TLR/MyD88/NF-κB inflammatory circuits and induction of tissue-repair programs, alongside a shift in macrophage phenotype toward resolution. With an encouraging biosafety profile and mitigated steroid side effects, D-PCB 30 represents a clinically promising strategy to overcome pulmonary barriers and to deliver targeted, effective therapies for acute inflammatory lung disease.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）