Tumor microenvironment: a mechanical force link

Nano carrier targeted drug delivery system has been widely concerned by many countries. Although papers published in this field have increased exponentially, no drug has come into the market successfully. Based on physicochemical and biological principles and through diffusion coefficient determination of nano carriers in different materials and particle sizes, this paper studies the different diffusion capacity of molecules and nanoparticles in aqueous media, as well as in vivo targeting process of the nanoparticles. After fundamental analysis of various theoretical misunderstanding for nano carriers targeted drug delivery system, we reveal that active targeting nanoparticles could not improve tumor targeting efficiency as their original designations. Then we draw a conclusion that EPR effect is only applicable for drug molecules and nano carriers with sufficient diffusion capacity, and propose new strategies for more feasible nano carriers targeted delivery, including environment-specific responded targeting drug release, improving the nano carrier diffusion capacity, using macrophage phagocytosis capturing NPs to achieve the target drug delivery, and step-by-step targeting strategy. nano carrier, active targeting, high efficient target, diffusion coefficient, EPR effect

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Section: 利用巨噬细胞固有的吞噬作用捕获Nps 实现靶向药物递送unclassified

Initial analysis of nano carrier targeted drug delivery system: misunderstanding, barriers and strategy

Mei

Gao

et al. 2016

Sci. Sin.-Vitae

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A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

Liu

Yang

et al. 2017

Sci. China Life Sci.

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Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway. In this study, we established a high-profile compounds library and certificated a novel compound named N-(N-pyrrolidylacetyl)-9-(4-bromobenzyl)-1,3,4,9-tetrahydro-β-carboline (YF-452), which remarkably inhibited the migration, invasion and tube-like structure formation of human umbilical vein endothelial cells (HUVECs) with little toxicity invitro. Rat thoracic aorta ring assay indicated that YF-452 significantly blocked the formation of microvascular exvivo. In addition, YF-452 inhibited angiogenesis in chick chorioallantoic membrane (CAM) and mouse corneal micropocket assays. Moreover, YF-452 remarkably suppressed tumor growth in xenografts mice model. Furthermore, investigation of molecular mechanism revealed that YF-452 inhibited VEGF-induced phosphorylation of VEGFR2 kinase and the downstream protein kinases including extracellular signal regulated kinase (ERK), focal adhesion kinase (FAK) and Src. These results indicate that YF-452 inhibits angiogenesis and may be a potential antiangiogenic drug candidate for cancer therapy.

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Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma

Modi

Kulkarni

2020

European Journal of Medicinal Chemistry

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Tumor microenvironment: a mechanical force link

Cited by 4 publications

References 10 publications

Initial analysis of nano carrier targeted drug delivery system: misunderstanding, barriers and strategy

Initial analysis of nano carrier targeted drug delivery system: misunderstanding, barriers and strategy

A novel synthetic small molecule YF-452 inhibits tumor growth through antiangiogenesis by suppressing VEGF receptor 2 signaling

Discovery of VEGFR-2 inhibitors exerting significant anticancer activity against CD44+ and CD133+ cancer stem cells (CSCs): Reversal of TGF-β induced epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma

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