Self-Assembled Supramolecular Nanogels as a Safe and Effective Drug Delivery Vector for Cancer Therapy

Simple construction and manipulation of low-molecular-weight supramolecular nanogels, based on the introduction of multiple hydrogen bonding interactions, with the desired physical properties to achieve effective and safe delivery of drugs for cancer therapy remain highly challenging. Herein, a novel supramolecular oligomer cytosine (Cy)-polypropylene glycol containing self-complementary multiple hydrogen-bonded Cy moieties is developed, which undergoes spontaneous self-assembly to form nanosized particles in an aqueous environment. Phase transitions and scattering studies confirm that the supramolecular nanogels can be readily tailored to obtain the desired phase-transition temperature and temperature-induced release of the anticancer drug doxorubicin (DOX). The resulting nanogels exhibit an extremely high load carrying capacity (up to 24.8%) and drug-entrapment stability, making the loading processes highly efficient. Importantly, in vitro cytotoxicity assays indicate that DOX-loaded nanogels possess excellent biosafety for drug delivery applications under physiological conditions. When the environmental temperature is increased to 40 °C, DOX-loaded nanogels trigger rapid DOX release and exert cytotoxic effects, significantly reducing the dose required compared to free DOX. Given its simplicity, low cost, high reliability, and efficiency, this newly developed temperature-responsive nanocarrier has highly promising potential for controlled release drug delivery systems.