Multifunctional DNA Nanogels for Aptamer-Based Targeted Delivery and Stimuli-Triggered Release of Cancer Therapeutics.

Targeted, stimulus-responsive DNA nanogels hold considerable promise for cancer therapeutics. To expand their functionality including thermoresponsiveness, here, multifunctional DNA nanogels are developed for potential application toward cancer-targeted delivery and stimuli-responsive release of cancer therapeutics. Three types of functionalized DNA nanobuilding units are formed into DNA nanogels of ≈200 nm via sequence-dependent self-assembly. The sequence-dependent assembly of nanobuilding units is precisely designed for controlled assembly and thermal disassembly at physiological temperatures. The supramolecular structure exhibits multifunctionalities including temperature-induced disassembly, aptamer-mediated cancer cell targeting, and light-triggered temperature increase. The nanogels support co-loading of cancer therapeutics including anti-sense oligonucleotides and doxorubicin along with stimuli-responsive release of loaded drugs through temperature-responsive structural disassembly and pH-responsive deintercalation. The nanogels exhibit efficient aptamer-mediated cancer-specific intracellular delivery and combinational anticancer effects upon light triggering. The developed DNA nanogels, thus, constitute potential noncationic nanovectors for targeted delivery of combinational cancer therapeutics.