Therapeutic Nanocarriers with Hydrogen Peroxide-Triggered Drug Release for Cancer Treatment

Abstract

Chemotherapy is an important modality in cancer treatment. The major challenge of recent works in this research field is to develop new types of smart nanocarriers that can respond selectively to cancer cell-specific conditions and realize rapid drug release in target cells. In the present study, a reactive oxygen species-responsive nanocarrier has been successfully self-assembled from an amphiphilic hyperbranched polymer consisting of alternative hydrophobic selenide groups and hydrophilic phosphate segments in the dendritic backbone. Because the hydrophobic selenide groups transformed into the hydrophilic selenone groups after oxidation under the exclusive oxidative microenvironment within cancer cells, the amphiphilic hyperbranched precursors become hydrophilic ones. As a result, the nanocarriers were rapidly disassembled in target cells, resulting in fast intracellular drug release. The hydrophilic products of oxidation can be degraded into harmless small molecular species via the enzymatic digestion of the phosphate segments and then eliminated by renal excretion. Meanwhile, the reactive selenium-containing nanocarrier possesses a potent intrinsic anticancer effect since selenium compounds can produce antitumor metabolites which induce apoptosis of cancer cells efficiently. Therefore, this type of therapeutic nanocarriers with a unique drug release mechanism based on an amphiphilic-to-hydrophilic transition provides a new platform for targeted drug delivery and combined therapy.