New power of self-assembling carbonic anhydrase inhibitor: Short peptide–constructed nanofibers inspire hypoxic cancer therapy

Abstract

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.

A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer

“…The 3 proteins selected in the previous study (carbonic anhydrase 1 [CAH 1], neural cell adhesion molecule L1-like protein [NCHL1], and apolipoprotein C-1 [APOC1]) exhibited differences in concentration between breast cancer patients and healthy individuals [13]. Changes in blood concentration of the three proteins in breast and other cancers are presented in Supplementary Table 1 [1415161718192021] and the characteristics of each protein are mentioned in Supplementary Table 2. Algorithm optimization and validation using new samples were performed using these three markers.…”

Designing Hypoxia‐Responsive Nanotheranostic Agents for Tumor Imaging and Therapy

“…With the similar chemical structure of SD, our group used another CA IX inhibitor (benzenesulfonamide) to design a CA IX‐targeted, self‐assembling, small molecule, peptide‐based hydrogel to treat hypoxic tumor cells and enhance the therapeutic effects of DOX ( Figure ). [ 103 ] Modified to possess a carbonic anhydrase inhibitor, the small molecule peptide exclusively self‐assembles to form nanofibers on the surface of hypoxic tumor cells. These nanofibers can induce endocytosis and further increase their size in the more acidic environment of lysosomes.…”

“…Reproduced with permission of CC‐BY‐NC license 4.0. [ 103 ] Copyright 2019, The Authors. Published by AAAS.…”

Detection of a multi‐disease biomarker in saliva with graphene field effect transistors

“…Carbonic anhydrases (CAs) are a family of enzymes that catalyse the reversible reaction of carbon dioxide and water into bicarbonate and protons (Krishnamurthy et al, 2008). Several studies have pointed to the importance of the CAs and their inhibitors as an indicator for various diseases (Finkelmeier et al, 2018; Koutnik et al, 2017; Li et al, 2019; Mehta et al, 2018; Zamanova et al, 2019). Of particular importance is the human isozyme CA1, which has been identified as a potential marker of various cancers (breast, oral, colorectal, lung, prostate), ankylosing spondylitis, diabetes, Sjogren's syndrome and pancreatitis (Bánová Vulić et al, 2019; Chang et al, 2010, 2012; Frulloni et al, 2000; Giusti et al, 2007; Hu et al, 2007; Inagaki et al, 1991; Kardoush et al, 2017; Lee et al, 2015; Liu et al, 2012; Peng et al, 2012; Ryu et al, 2006; Torella et al, 2014; Wang et al, 2016; Zheng et al, 2015).…”