Development of an interactive tumor vascular suppression strategy to inhibit multidrug resistance and metastasis with pH/H2O2 responsive and oxygen-producing nanohybrids.

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Development of an interactive tumor vascular suppression strategy to inhibit multidrug resistance and metastasis with pH/H2O2 responsive and oxygen-producing nanohybrids.

J Mater Chem B. 2019 Aug 07;7(31):4784-4793

Authors: Du B, Ding X, Wang H, Du Q, Xu T, Huang J, Zhou J, Cheng G

Abstract
An ideal cancer therapeutic strategy should not only reverse multidrug resistance (MDR), but also prevent cancer metastasis. In this study, bovine serum albumin (BSA) was hybridized with Mn2+via biomineralization to develop a hybrid protein oxygen nanocarrier, which contained doxorubicin (DOX) and small interfering RNA (siRNA). The nanohybrid has the function of producing oxygen and chemotherapy synergistic gene therapy. FA-BSA-MnO2/DOX/siRNA was favorable for increasing the sensitivity of MCF-7/ADR cells to DOX. Moreover, FA-BSA-MnO2/DOX/siRNA NPs were also able to generate oxygen (O2) by reaction with endogenous hydrogen peroxide (H2O2) in tumor, thereby down-regulating the expression of hypoxia inducible factor-1α (HIF-1α), and then the expression of the vascular endothelial growth factor (VEGF) was down-regulated. At the same time, siRNA can directly or indirectly suppress the expression of the VEGF and HIF-1α. Therefore, the combination of two pathways and the chemo-gene therapy strategy can interactively overcome tumor hypoxia-associated MDR and metastasis, which will enhance therapeutic efficacy in the future.

PMID: 31389949 [PubMed - in process]