INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
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IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
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癌症研究
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药物递送系统
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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
JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Xinyuan Zhou,Pan Zhang,Nan Liu,Xiao Zhang,Hui Lv,Wei Xu,Meirong Huo
Pancreatic cancer (PC) carries a poor prognosis among all malignancies and poses great challenges to clinical drug accessibility due to the severely fibrotic and hypoxic tumor microenvironment (TME). Therein, cancer-associated fibroblasts (CAFs), which are extremely abundant in PC, play a key role in forming the complex PC microenvironment. Therefore, a highly efficient TME reprogramming therapeutic paradigm that can specifically inhibit CAF function is urgently needed. Herein, we successfully developed a novel CAF-tailored nanosystem (Dex-GP-DOCA, DPD) loaded with a potent anti-fibrosis flavonoid compound (Quercetin, QUE), which possesses biological responsiveness to fibroblast activation protein alpha (FAP-α), prolonged TME remodeling and enhancement of clinical chemotherapeutics. Specifically, DPD/QUE allowed for extracellular matrix (ECM) reduction, vessel normalization, hypoxia-induced drug resistance reversal, and blockade of Wnt16 paracrine in CAFs. More importantly, this chemotherapy conducive microenvironment persisted for at least 8 days following treatment with DPD/QUE. It should also be noted that the effective and prolonged microenvironment modulation induced by DPD/QUE significantly improved the chemotherapy sensitivity of Abraxane and gemcitabine, the first-line chemotherapeutic drugs for PC, with inhibition rates increasing from 37.5% and 40.0% to 87.5% and 85.2%, respectively. Overall, our CAFs-targeted nanosystem showed promising prospects for remodeling the TME and facilitating chemotherapy for refractory pancreatic cancer.
研究领域:
肿瘤学
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药理学
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纳米技术
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-18
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IF 16.6
Li Zheng,Zhu Yabo,Zeng Haowen,Wang Chong,Xu Chen,Wang Qiang,Wang Huimin,Li Shiyou,Chen Jitang,Xiao Chen,Yang Xiangliang,Li Zifu
Nanomedicine has been developed for cancer therapy over several decades, while rapid clearance from blood circulation by reticuloendothelial system (RES) severely limits nanomedicine antitumour efficacy. We design a series of nanogels with distinctive stiffness and investigate how nanogel mechanical properties could be leveraged to overcome RES. Stiff nanogels are injected preferentially to abrogate uptake capacity of macrophages and temporarily block RES, relying on inhibition of clathrin and prolonged liver retention. Afterwards, soft nanogels deliver doxorubicin (DOX) with excellent efficiency, reflected in high tumour accumulation, deep tumour penetration and outstanding antitumour efficacy. In this work, we combine the advantage of stiff nanogels in RES-blockade with the superiority of soft nanogels in drug delivery leads to the optimum tumour inhibition effect, which is defined as mechano-boosting antitumour strategy. Clinical implications of stiffness-dependent RES-blockade are also confirmed by promoting antitumour efficacy of commercialized nanomedicines, such as Doxil and Abraxane.
研究领域:
药理学
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纳米技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2023
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IF 6
Lan Tang,Kaijuan Huang,Wenhui Jiang,Lulu Fu,Ran Zhang,Liting Shen,Zhimin Ou,Ye Huang,Zhenhai Zhang
D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) is a commonly used nonionic surfactant used as a pharmaceutical carrier in different drug delivery systems. TPGS can reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) and also has anticancer activities. It suggests that when designing antitumor drug preparation, it’s necessary to take into account the antitumor activity of TPGS. Our in vivo studies showed that TPGS exerted the strongest cytotoxicity in MCF-7-ADR cells when compared with seven other tumor cell lines. The further study revealed TPGS caused apoptosis and blocked MCF-7 cell growth in G2/M phase. Mechanistic insights suggested that TPGS increased intracellular calcium ion concentrations, leading to apoptosis via the mitochondrial pathway. Furthermore, two in vivo experiments were performed. One was TPGS, and DOX solution was administered by tail vein injection on MCF-7-ADR tumor bearing nude mice. The other was temperature sensitive TPGS gel (TPGS-TG) was administered by intratumoral injection on MCF-7-ADR tumor bearing nude mice combined with paclitaxel albumin nanoparticles (Abraxane®) administered by tail vein injection. The findings confirmed that TPGS could play its role in anti-tumor to reduce the toxicity of chemotherapeutic drugs and improve the efficiency of drug-resistant tumors, thereby enhancing the development of safe oncology therapeutics.
研究领域:
药理学
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肿瘤学
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药物递送系统
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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