ACS Applied Materials & Interfaces
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2020
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IF 8.758
Jia Liu,Lei Zhao,Lin Shi,Ye Yuan,Daan Fu,Zhilan Ye,Qilin Li,Yan Deng,Xingxin Liu,Qiying Lv,Yanni Cheng,Yunruo Xu,Xulin Jiang,Guobin Wang,Lin Wang,Zheng Wang
Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attributed to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nanostrategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors’ adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors’ adverse effects, a stealthy, sequentially responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of an extracellular-tumor-acidity-responsive polymer shell (PEG-b-PLLDA), pH/redox dual-responsive mesoporous silica nanoparticle-based carriers (MSNs-SS-Py), and cationic β-cyclodextrin-PEI (CD-PEI) gatekeepers. The PEG-b-PLLDA corona makes RCMSNs stealthy with prolonged blood circulation time. Once tumors are reached, extracellular acidity degrades PEG-b-PLLDA, reversing nanosystem’s surface charges to be positive, which drastically improves RCMSNs’ tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione and functionally act as a P-gp inhibitor, dampening P-gp’s efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverses MDR in vitro. Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.
研究领域:
纳米技术
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药学
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肿瘤学
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生物医学工程
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药物递送系统
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 13
·2338-2350
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IF 4.872
Yuanyuan Guo,Boning Niu,Qingle Song,Yongdan Zhao,Yuling Bao,Songwei Tan,Luqin Si,Zhiping Zhang
Developing multifunctional nanoparticles (NPs) to improve therapeutic efficacy is highly desirable in cancer therapy. In an attempt to respond to such a challenge, a novel copolymer, D-α-tocopherol polyethylene glycol succinate-SS-poly(lactide) (TPGS-SS-PLA) with a disulfide linkage between the TPGS and PLA units, was synthesized for paclitaxel (PTX) delivery. PTX-loaded NPs were fabricated using a nanoprecipitation method to form a particle size of ∼130 nm with good in vitro stability, which can be disassociated under intracellular reductive conditions to release PTX rapidly. The detached TPGS can further promote the drug retention and cytotoxicity through its P-glycoprotein inhibiting property. Integrin-specific targeting peptide, cyclic RGD (cRGD), was further conjugated to the surface of the NPs for targeting the drug delivery. The RGD-decorated NPs exhibited enhanced cellular uptake, PTX accumulation and cell cytotoxicity as compared to non-targeted NPs on murine melanoma B16F10 cells, PTX-sensitive human ovarian A2780 cells and PTX-resistant A2780/T cells. In vivo evaluation of the targeted NPs further showed an extended half-life, increased AUC (area under the concentration–time curve), and significant tumor growth inhibition in mouse sarcoma S180- and B16F10-tumor bearing mice, with reduced side effects as compared to Taxol® and non-targeted NPs. These results indicate that the RGD decorated redox-sensitive NPs could deliver chemotherapies specifically inside the cell via receptor-mediated endocytosis with enhanced efficacy, especially in integrin αvβ3/αvβ5-rich tumor cells. Such a targeted nanocarrier against receptor clustering prepared from a non-cytotoxic and biodegradable copolymer might have great potential in cancer treatment.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 50
·2104473
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IF 18.808
DanRong Hu,Meng Pan,Yun Yang,Ao Sun,Yu Chen,LiPing Yuan,KangKang Huang,Ying Qu,ChengQi He,Quan Wei,ZhiYong Qian
Focal therapy, or partial gland ablation, represents the middle ground between active surveillance and definitive treatment strategies against localized prostate cancer (PCa), among which the ultrasound- and light-mediated focal therapies are quite promising. Herein, for the first time in the literature, a novel polysaccharide-based nanoprodrug is fabricated for synergistic sonodynamic therapy and phototherapy against localized PCa. Specifically, the cyanine dye IR806 is conjugated to chondroitin sulfate (CS) via disulfide linkages to obtain CS-ss-IR806 (CSR) conjugates, which then self-assemble to form CSR nanoparticles (NPs) with properties of enhanced endocytosis, redox/hyaluronidase-responsiveness, and mitochondria-targeted ability. In contrast to free sensitizers, CSR NPs reveal dramatically enhanced water solubility, substantially lower dark toxicity, and superior biocompatibility. Encouragingly, favorable hyperthermia and high reactive oxygen species generation are observed on exposing CSR NPs to combined sono/photoirradiation. In a PCa tumor-bearing mice model, intratumoral injection with a markedly low dose of CSR NPs followed by dual-irradiation results in superior trimodal anticancer efficacy when compared with either monoirradiation strategy. Such synergistic antitumor efficacy is further demonstrated to be associated with the common and complementary mechanisms of sonotherapy and phototherapy. This work provides a promising approach as a next-generation focal therapy strategy against localized PCa.
研究领域:
癌症研究
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纳米技术
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生物医学工程
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药学
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治疗学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Xinyi Liang,Aiyang Zhang,Wei Sun,Jiao Lei,Xiaoli Liu,Zengchao Tang,Hong Chen
The endothelial glycocalyx is a carbohydrate–rich layer overlying the outermost surface of endothelial cells. It mediates intercellular interactions by specific chemical compositions (e.g., proteoglycans containing glycosaminoglycan (GAG) side chains) and micro/nanotopography. Inspired by the endothelial glycocalyx, we fabricated a series of glycocalyx–mimetic surfaces with tunable chemical compositions (GAG–like polymers with different functional units) and topographical structures (micro/nanopatterns with pillars different in size). The combination of micro/nanopatterns and GAG–like polymers was flexibly and precisely controlled by replica molding using silicon templates (Si templates) and visible light–initiated polymerization. Human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs) were suppressed on surfaces modified with polymers of 2–methacrylamido glucopyranose (MAG) but promoted on surfaces modified with polymers of sodium 4–vinyl–benzenesulfonate (SS) and copolymers of SS and MAG. Surface micro/nanopatterns showed highly complicated effects on surfaces grafted with different GAG–like polymers. Moreover, the spread of HUVSMCs was highly promoted on all flat/patterned surfaces containing sulfonate units, and the elongation effect was stronger on surfaces with smaller pillars. On all the flat/patterned surfaces modified with GAG–like polymers, the adsorption of human vascular endothelial growth factor (VEGF) and human basic fibroblast growth factor (bFGF) was improved, and the amount of VEGF and bFGF absorbed on patterned surfaces containing sulfonate units decreased with pattern dimensions. The decreasing trend of VEGF and bFGF adsorption was in accordance with HUVEC density, suggesting that glycocalyx–mimetic surfaces influence the adsorption of VEGF and bFGF and further influence the growth behavior of vascular cells.
研究领域:
生物材料
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组织工程
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细胞生物学
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生物医学工程
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DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 39
·28753-28767
·
IF 3.9
Yu Hu,Tian Lan,Ji Li,Lingjun Li,Jizheng Song
Cantharidin (CTD) has been widely used to treat hepatocellular carcinoma (HCC) in clinical practice. However, the current CTD preparations may induce hepatic and renal damage due to their non-specific distribution. Therefore, redox-sensitive polymer Pluronic F127-disulfide bond-poly(D,L-lactide) (F127-SS-PDLA) and active targeting polymer F127-glycyrrhetinic acid (F127-GA) were synthesized to prepare mixed micelles (GA/F127-SS-PDLA/CTD) for effective delivery of CTD. Fourier transform infrared (FTIR) spectroscopy and 1H nuclear magnetic resonance (1H-NMR) spectroscopy were used to verify the successful synthesis of F127-SS-PDLA and F127-GA. During the preparation, this study was the first to screen the density of GA by cellular uptake assay. The results indicated that mixed micelles with 10% and 15% F127-GA (weight fraction) exhibited superior cellular uptake in comparison to micelles with 5% and 20% F127-GA. GA/F127-SS-PDLA/CTD micelles prepared by thin film hydration method demonstrated excellent drug loading capacity for CTD (16.12 ± 0.11%). The particle size and zeta potential of GA/F127-SS-PDLA/CTD micelles were 85.17 ± 1.24 nm and −11.71 ± 0.86 mV, respectively. Hemolysis and stability assay showed that the mixed micelles had good blood compatibility and could remain stable for 30 days at 4 °C. The redox-sensitivity of GA/F127-SS-PDLA/CTD micelles in vitro was verified under reducing conditions through dynamic light scattering (DLS) and an in vitro drug release experiment, which showed obvious particle size variation and rapid drug release ability. In cellular experiments, GA/F127-SS-PDLA/CTD micelles could induce superior cytotoxicity, apoptosis and intracellular reactive oxygen species (ROS) levels compared with free CTD, non-sensitive F127-PDLA/CTD micelles and redox-sensitive F127-SS-PDLA/CTD micelles. The cellular uptake ability of nile red-labeled GA/F127-SS-PDLA micelles, which was evaluated via fluorescent microscope and flow cytometry, indicated that the modification of GA significantly increased micelle uptake in HepG-2 cells. Consequently, GA/F127-SS-PDLA/CTD micelles could be considered as a satisfactory drug administration strategy in the treatment of HCC.
研究领域:
药学
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生物医学工程
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肿瘤学
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材料科学
✓ 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）