Injectable Nanocomposite Hydrogels With Co-Delivery of Oxygen and Anticancer Drugs for Higher Cell Viability of Healthy Cells Than Cancer Cells Under Normoxic and Hypoxic Conditions

Abstract

Injectable nanocomposite hydrogels (NC hydrogels) have the potential to be used for minimally invasive local drug delivery. In particular, pH-sensitive injectable NC hydrogels can be used in cancer treatment to deliver high doses of anticancer drugs to the target site in cancer tissue without damaging healthy tissue. Recent studies have shown that in addition to stimuli-responsive delivery of anticancer drugs to cancer cells, oxygen delivery to the hypoxic environment of cancer tissue can lead to advanced effects, as hypoxia and an acidic pH are common characteristics of cancer tissue. However, few studies have investigated the effects of simultaneous administration of oxygen (O2) and pH-dependent anticancer drugs via injectable NC hydrogels on the viability of healthy and cancer cells under normoxic and hypoxic conditions. In this context, we describe the synthesis of injectable NC hydrogels composed of pH-responsive nanomaterials carrying oxygen and anticancer drugs. Our system provides sustained O2 release and pH-responsive sustained release of anticancer drugs for 15 and 30 d, respectively. Moreover, O2 delivery and/or simultaneous delivery of O2 and anticancer drug resulted in higher cell survival of healthy fibroblast cells than malignant Colo-818 cells under hypoxic conditions (1% O2) after 7 d of incubation.