New power of self-assembling carbonic anhydrase inhibitor: Short peptide–constructed nanofibers inspire hypoxic cancer therapy
Jiayang Li, Kejian Shi, Zeinab Farhadi Sabet, Wenjiao Fu, Huige Zhou, Shaoxin Xu, Tao Liu, Min You, Mingjing Cao, Mengzhen Xu, Xuejing Cui, Bin Hu, Ying Liu and Chunying Chen
Science Advances 06 Sep 2019: Vol. 5, no. 9, eaax0937 DOI: 10.1126/sciadv.aax0937
Carbonic anhydrase (CA) IX overexpresses exclusively on cell membranes of hypoxic tumors, regulating the acidic tumor microenvironment. Small molecules of CA inhibitor modified with short peptide successfully achieve CA IX–targeted self-assembly that localizes CA inhibitors on hypoxic cancer cell surfaces and enhances their inhibition efficacy and selectivity. CA IX–related endocytosis also promotes selective intracellular uptake of these nanofibers under hypoxia, in which nanofiber structures increase in size with decreasing pH. This effect subsequently causes intracellular acid vesicle damage and blocks protective autophagy. The versatility of tunable nanostructures responding to cell milieu impressively provokes selective toxicities and provides strategic therapy for hypoxic tumors. Moreover, in vivo tests demonstrate considerable antimetastatic and antiangiogenesis effects in breast tumors, and particularly remarkable enhancement of antitumor efficacy in doxorubicin administration. With its biocompatible components and distinctive hypoxia therapies, this nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy.
Circular dichroism, biochemistry, nanomaterials, nanofibers, cancer, tumor