Development of Highly Sensitive Molecular Blocks at Cancer Microenvironment for Rapid Cancer Cell Death

Abstract

Improving the efficiency and selectivity of drug delivery systems (DDS) is still a major challenge in cancer therapy. Recently, the low transport efficiency of anticancer drugs using a nanocarrier due to the elimination of the carriers from the blood circulation and the blocking by tumor stromal tissues surrounding cancer cells has been reported. Furthermore, multiple steps are required for their intracellular delivery. We recently reported a cancer microenvironment-targeting therapy termed molecular block (MB) which induced cancer cell death by a pH-driven selfaggregation and cell membrane disruption at tumor microenvironment. The MB were designed to disperse as nanoscale assemblies in the bloodstream for efficient circulation and penetration through the stromal tissues. When the MBs reach the tumor site, they selfassembled in microscale aggregates on the cancer cell surfaces in response to the cancer microenvironment and induced cancer cell death. However, in vivo study in mice showed that the MB could not efficiently accumulate at the tumor site because slight hydrophobic aggregations in the bloodstream might potentially be the reason for the off-target accumulation. In this study, we optimize the hydrophilic−hydrophobic balance of MB for avoiding the offtarget accumulation and for gaining higher sensitivity to the cancer microenvironment at weak acid condition. Copper-free click reaction with propiolic acid was used to reduce the hydrophobicity of the main chain and obtain higher responsive MB at cancer microenvironment for rapid cell killing. The optimized MB can be considered as a promising approach for an improved cancer cell targeting.

Preface to the Françoise M. Winnik Special Issue

“…This special issue celebrates her career with contributions from colleagues across the world. The included papers represent many topical areas, including microgels, elastomers, microbubbles, microemulsions, supramolecular assemblies, and thin films, with critical physical properties enabling applications as broad-ranging as carbon capture, medicine, and electronics. − Nonetheless, many of the papers are fundamental in nature, reflecting Professor Winnik’s enduring commitment to and interest in basic colloid and interfacial science.…”