INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Wei-liang Chen,Shu-di Yang,Fang Li,Ji-zhao Li,Zhi-qiang Yuan,Wen-jing Zhu,Yang Liu,Xiao-feng Zhou,Chun Liu,Xue-nong Zhang
Internal stimuli, such as intracellular lysosomal pH, enzyme, redox and reduction, can be applied to improve biological specificity of chemotherapeutic drugs for cancer therapy. Thus, functionalized copolymers based on their response to specific microenvironment of tumor regions have been designed as smart drug vesicles for enhanced anti-cancer efficiency and reduced side effects . Herein, we reported dually pH/reduction-responsive novel micelles based on self-assembly of carboxymethyl chitosan-cysteamine- N -acetyl histidine (CMCH-SS-NA) and doxorubicin (DOX). The tailor-made dually responsive micelles demonstrated favorable stability in normal physiological environment and triggered rapid drug release in acidic and/or reduction environment. Additionally, the nanocarriers responded to the intracellular environment in an ultra-fast manner within several minutes, which led to the pinpointed release of DOX in tumor cells effectively and ensured higher DOX concentrations within tumor areas with the aid of targeted delivery, thereby leading to enhanced tumor ablation. Thus, this approach with sharp drug release behavior represented a versatile strategy to provide a promising paradigm for cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qing Liu,Zhu Jin,Wei Huang,Yuanyuan Sheng,Zhongmin Wang,Shengrong Guo
To overcome the different extra-/intracellular barriers in gene delivery, tumor-targeted and pH/redox-responsive ternary polyplexes with charge-conversional properties were prepared through a modular self-assembly strategy. Firstly, the thiolated trimethylated chitosan (TMC-SH) was synthesized to crosslink and condense pDNA through electrostatic interaction and disulfide formation, which obtained the TMC-SS/pDNA binary polyplexes with redox-responsive gene release. To further endow the binary polyplexes with tumor targeting and endo/lysosomal pH-triggered charge-reversal properties, a folate conjugated cis -aconitic amide-polyethylenimine (FA-PEI-AcO) was synthesized to shield the positive TMC-SS/pDNA, generating the FA-PEI-AcO/TMC-SS/pDNA ternary polyplexes with a size of ~190 nm and negative surface-charges. The ζ-potential of the polyplexes was stable at physiological pH and increased rapidly from -14 mV to + 20 mV at pH 5.5 (endo/lysosomal pH) due to the breakages of acid-liable amide bonds and the subsequent de-shielding of FA-PEI-AcO layers, which might benefit the endo/lysosomal escape of the polyplexes. Afterward, the polyplexes could redox-responsively release gene at higher intracellular concentrations of glutathione. By taking advantage of such multi-responses, significantly enhanced transfection efficiency was achieved in vitro in Hela cells for the ternary polyplexes. These results suggested that the newly developed polyplexes had potential application for gene delivery.
研究领域:
生物材料学
·
分子生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2019
·
IF 6.361
Junqiang Zhao,Caixia Yan,Ze Chen,Jinjian Liu,Huijuan Song,Weiwei Wang,Jianfeng Liu,Ning Yang,Yiping Zhao,Li Chen
Multifunctional nanoparticles (NPs) with high blood-stability, tumor-targeting ability, and stimuli-bioresponsive drug release behaviors are urgently demanded. Herein, folic acid (FA) and galactose (GAL) functionalized, core-crosslinked NPs (CC NPs) with dual-targeting and pH/redox-bioresponsive properties were developed based on amphiphilic FA-poly(6-O-methacryloyl- d -galactopyranose)- b -poly[2-(diisopropylamino) ethyl methacrylate- co -pyridyl disulfide methylacrylate] [FA-PMAgGP- b -P(DPA- co -PDEMA), termed as FA-PMgDP] block copolymers , and then investigated for facilitated hepatoma-targeting delivery of doxorubicin (DOX). A series of PMgDP copolymers were synthesized though two-step RAFT copolymerization followed by acid-induced acetal deprotection reaction. Their well-defined chemical structures and compositions were characterized by 1 H NMR and gel permeation chromatography . Nano-sized, non-crosslinked PMgDP NPs (PMgDP NC NPs) with sizes of less than 25 nm in aqueous solution were self-assembled via the solvent exchange method, and PMgDP CC NPs were readily prepared in the presence of dithiothreitol. The drug-loading content of PMgDP CC NPs was up to 15.8% and its entrapment efficiency was 89.0%. In normal physiological conditions, 11.6% of DOX was released from DOX-loaded PMgDP CC NPs at 25 h, whereas in analogous intracellular microenvironment, 95.5% was released at 11 h owing to the acid-induced protonation of tertiary amine and reductive cleavage of disulfide bond in the hydrophobic core. In a cellular uptake study, FA and GAL-mediated, active, dual-targeted DOX-loaded FA-PMgDP CC NPs showed a 3.54-fold increase in cellular uptake efficiency to HepG2 cells compared to that of shown by single GAL-targeted, DOX-loaded PMgDP NC NPs. Results of in vitro cytotoxicity study showed that blank FA-PMgDP CC NPs exhibited good biocompatibility, whereas dual-targeting DOX-loaded FA-PMgDP CC NPs increased cell apoptosis. Therefore, the above results indicated that the well-constructed FA-PMgDP CC NPs with multi-synergistic effect may serve as new nanocarriers in the field of precise hepatoma-targeting drug delivery.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Zhengzhong Wu,Bin Chen,Ziying Gan,Fan Chen,Xianglin Luo
The effective accumulation at tumor sites and endocytosis by tumor cells for anticancer agents in carriers are essential in successful cancer therapy, and both of the processes are affected by the surface charge of drug carriers. In this study, vitamin C (VC) was employed as an “exogenous switch” to trigger the surface charge conversion of DOX-loaded micelles to obtain a better antitumor effect. T micelles formed by poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL–PDEA-ss-PMPC) turned their ζ potentials from +1 mV to +18 mV under treatment of 20 mM VC, while the ζ potentials of control R micelles formed by PCL-ss-P(DEA-r-MPC) almost remained unchanged under the same condition. DOX-loaded T@DOX and R@DOX had high DLCs of 12% and 13.8%, respectively, and both showed an accelerated drug release in a reductive environment (10 mM GSH or 20 mM VC) at pH 5.0. Notably, due to the surface charge conversion and fast drug release triggered by VC, T@DOX/VC (T@DOX was pretreated by VC) showed an enhanced cytotoxicity and cellular uptake superior to T@DOX, R@DOX, and R@DOX/VC. T@DOX/VC also displayed the in vivo antitumor effect well, which was comparable to DOX·HCl but with less toxic side effects than DOX·HCl. In summary, VC as an exogenous trigger can induce a better antitumor effect of drug-loaded micelles with a suitable polymer structure by charge conversion, and T@DOX/VC has shown to be as a promising approach to achieve potent treatment of tumors.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2021
·
IF 4.774
Nanxia Zhang,Weixing Liu,Zhipeng Dong,Yunxue Yin,Jun Luo,Tao Lu,Weifang Tang,Yue Wang,Yonghu Han
Tumor microenvironment (TME) responsive polymeric micelles are promising carriers for drug delivery. In order to meet the needs of various applications, multifarious TME-responsive switches are used to construct smart polymeric micelles, which causes the complexity and corpulence of the polymeric micelle system and increases the difficulty of preparation. In this study, we designed and synthesized an ingenious TME-responsive switch through grafting disulfide bond-modified piperidinepropionic acid (CPA) on copolymer poly(ethylene glycol)-b-poly(aspartate)(PEG-b-PAsp) and built a novel pH/reduction-responsive PEG-b-PAsp-g-CPA polymeric micelle delivery system. The CPA-pendants can reverse the surface charge of the polymeric micelle from negative to positive at pH 6.5 because of the protonation of piperidine groups, thereby enhancing the internalization of cell. Subsequently, more piperidine groups are protonated at pH 5.0 which will increase the hydrophilicity of polymeric micelles and cause the hydrophobic core to swell, thus making the disulfide bonds packed in the core to be more easily broken by GSH. With the synergistic effect of the pH-triggered protonation of piperidine groups and reduction triggered break of disulfide bonds, the polymeric micelles will disintegrate and achieve efficient intracellular drug release. The TME-responsive polymeric micelles exhibited good biological safety, enhanced internalization, and rapid intracellular doxorubicin (DOX) release in vitro. Moreover, the PEG-b-PAsp-g-CPA/DOX polymeric micelles showed excellent antitumor efficacy and low systemic toxicity in lung tumor-bearing BALB/C mice. These results indicated that the novel integrated TME-responsive switch CPA helps the PEG-b-PAsp-g-CPA polymeric micelles to obtain excellent TME-responsiveness and antitumor drug delivery capabilities, while it also makes the preparation of TME-responsive polymeric micelles simpler and more convenient. This work provides a new idea for the architecture of TME-responsive polymeric micelles.
研究领域:
药学
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纳米技术
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癌症研究
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
·
2023
·
IF 3.2
Pan Jun,Cai Youzhi,Zhang Chi,Xu Sanzhong
Osteoarthritis (OA) remains a challenging condition due to limited drug bioavailability within the avascular and dense cartilage matrix. This study introduces a pH/redox-responsive nanogel for enhanced delivery of geraniol in OA therapy. We investigated geraniol's role in preventing chondrocyte matrix degradation and designed a pH/redox-responsive nanogel as a delivery platform. Our methods included Western blot, histological staining, and immunohistochemistry. Geraniol treatment reduced Keap1 expression while elevating Nrf2 and HO-1 levels, effectively inhibiting cartilage matrix degradation. The pH/redox-responsive nanogel further enhanced geraniol’s therapeutic impact. Our study demonstrates that geraniol encapsulated within a pH/redox-responsive nanogel mitigates OA by regulating oxidative stress and inflammation. This innovative approach holds potential as an effective OA therapeutic strategy.
研究领域:
药理学
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纳米技术
·
骨科
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Shumin Chen,Xiaoguo Ji,Mengyao Zhao,Jiayang Jin,Haiping Zhang,Liming Zhao
AZD9291 can prolong the survival of patients with non-small cell lung cancer. Unfortunately, resistance to AZD9291 is inevitable and hinders effectiveness. Studies showed the combination of Cyclosporin A (CsA) and AZD9291 could increase the efficacy of AZD9291, but the delivery efficiency of free drugs was limited. A chitooligosaccharide (COS) -based nanoparticle with enhanced delivery efficiency and endocytosis was constructed in this study. The results showed that this pH/redox cascade responsive nanoparticles improved therapeutic effect. The system is small and the surface charge changed from negative to positive according to the weakly acidic tumor microenvironment. After endocytosis, the nanoparticles decomposed and released AZD9291 and CsA in redox-rich cytoplasm. Experiments in vitro and in vivo proved that the nanoparticles overcame the biological barrier and significantly enhanced the anti-tumor effect of AZD9291. The novel multifunctional nanoparticle provides a way to overcome the drug resistance and the possibility of clinical application.
研究领域:
药学
·
纳米技术
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2023
·Vol. 25
·期 17
·12458-12468
·
IF 3.3
Chufen Yang,Delin Wang,Wenyao Liu,Zexiong Yang,Teng He,Fang Chen,Wenjing Lin
Aiming at achieving the concurrent performances of high loading, well controlled release and active targeted delivery, folate (FA) modified dual pH/reduction-responsive mixed polymeric micelles were rationally assembled using FA-PEG-PDEAEMA and PEG-SS-PCL by dissipative particle dynamics (DPD) simulations. The optimized polymers PEG112-PDEAEMA40, FA-PEG112-PDEAEMA40, and PEG112-SS-PCL70 were synthesized and characterized using 1H NMR, FT-IR and GPC, and their mixed micelles were applied for doxorubicin (DOX) delivery. The drug loading capacity (LC) and encapsulation efficiency (EE) values of the MIX1 (FA-PEG112-PDEAEMA40/PEG112-SS-PCL70) at a DOX/polymer feeding ratio of 15 mg/30 mg were 20.22% and 50.69%, which were higher than those of single polymer micelles and MIX2 (PEG112-PDEAEMA40/PEG112-SS-PCL70). Particle size distributions, mesoscopic morphologies, DPD simulations and in vitro drug release profiles all confirmed the well-controlled release performance of the DOX-loaded micelles formed by MIX1: slow DOX release with a cumulative release of 20.46% in the neutral environment and accelerated release with a cumulative release of 74.20% at pH 5.0 + 10 mM DTT within 120 h, which were similar to those of MIX2. Cytotoxicity assay found that both MIX1 and MIX2 blank micelles were biocompatible, and a superior inhibitory effect of the FA-modified DOX-loaded micelles MIX1 on HepG2 cells was found compared to that of free DOX and non-FA-modified DOX-loaded micelles MIX2. All of these confirmed the superiority of MIX1 micelles with high loading capacity, well controlled release, and enhanced inhibitory effects on HepG2 cells, which might be a prospective candidate for anticancer drug delivery.
研究领域:
药学
·
纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Pengfei Guo,Xiujuan Luan,Tao Wang,Linlin Hu,Weifen Zhang
For most degradable nanocarriers, precisely controlled delivery remains a challenge because the drug release is fast in neutral buffer solution. The unfavorable drug leakage could lead to serious toxicity. Thus, it is important to realize precise controlled delivery for nanocarriers with fast biodegradability but excellent stability in a neutral physiological environment. Here, a biodegradable pH/redox-responsive drug delivery system, quercetin (Que)-loaded and poly(ethylene glycol) (PEG)-modified manganese (Mn)-containing mesoporous silica nanoparticles (MSN), designated as PEG@MSN(Mn)@Que, was built for cancer therapy. Nanoparticles present a rough nanoscale spherical morphology with an average size of 107.2 nm and an ordered mesoporous structure. Quercetin has been successfully loaded with an efficiency of 46.47% and a drug release rate of 48.64%. Mn–O bonds were formed by doping Mn to the MSN framework at the molecular level, and the Mn-doping amount was 36.59%. The pH/redox-responsive cleavage of Mn–O bonds promotes the specific biodegradation of PEG@MSN(Mn)@Que and the controlled Que release in the tumor microenvironment. Especially, the degradation behaviors showed excellent stability of PEG@MSN(Mn)@Que in neutral conditions for 5 days, and the drug leakage was very low (only 5.65% of Que released), achieving the precisely controlled Que delivery. A high antitumor effect was simultaneously achieved by anticancer drug delivery mediated by PEG@MSN(Mn)@Que, and the high biocompatibility of nanoparticles was systematically demonstrated in vitro and in vivo. This work provides a feasible way to reduce side effects caused by drug leakage, improving the antitumor effect.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Panpan Song,Zhongxia Lu,Tianze Jiang,Wenwei Han,Xiangyan Chen,Xia Zhao
The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/ [email protected] ) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/ [email protected] are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4 + /CD8 + T cells by silencing PD-L1 expression. In vivo studies show that R/C/ [email protected] exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
生物医学工程
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yibing Yan,Fangxiang Song,Songye Li,Tingxian Li,Qian Li,Yan Li
Accurate pesticide application enhances efficiency, reduces usage and minimizes environmental risks. This study employed amino-functionalized degradable mesoporous organosilicon nanoparticles (DMON-N) as a carrier, with chitosan (CS) acting as a capping agent. Chemical cross-linking of CS with Cu 2+ through chelation promotes the formation of Cu 2+ -CS complexes. A pH/redox dual-responsive prochloraz (PRO) delivery system (Cu-CS@PRO-DMON, CCPD) was constructed and evaluated for its potential application in controlling rice sheath blight. The successful preparation of CCPD was confirmed through a series of physicochemical characterizations. The findings demonstrated that CCPD exhibited a high PRO loading capacity (29.09 %) and that PRO could be released from CCPD for an extended duration (up to 144 h) under the influence of acidity and glutathione promotion. Furthermore, CCPD demonstrated excellent wettability (measured contact angle: 63.52 ± 0.42°), adhesion (23.83 ± 2.59 mg/cm 2 ) and resistance to rainfall washout on rice leaves. CCPD demonstrated superior antimicrobial efficacy to prochloraz technical (PRO TC) material and prochloraz emulsion in water (PRO EW). The biosafety assessment revealed that CCPD exhibited minimal acute toxicity to zebrafish, no discernible toxicological effects on human bronchial epithelial cells and no notable impact on rice.
研究领域:
农业科学
·
纳米技术
·
植物病理学
·
环境科学
·
药学
✓ 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）