Facile synthesis of chitosan-based nanogels through photo-crosslinking for doxorubicin delivery

Chitosan-based nanogels are effective carriers for drug delivery due to their biocompatibility and biodegradability. However, the chemically cross-linked nanogels usually require complicated procedures or tough conditions. Herein, we report a simple approach to generate chitosan-based nanogels by photo-crosslinking of poor solvent-induced nanoaggregates without requiring any emulsifying agent, catalyst, or external crosslinker. O-nitrobenzyl alcohol-modified carboxymethyl chitosan was synthesized and self-crosslinked into the nanogels in a mixed solution of ethanol and water under 365 nm light irradiation due to UV-induced primary amine and o-nitrobenzyl alcohol cyclization. The nanogels (CMC-NBA NPs) and lactobionic acid-decorated nanogels (LACMC-NBA NPs) displayed a uniform diameter (~200 nm) and excellent stability under physiological conditions. Notably, the nanogels exhibited a high loading content (~28 %) due to π-π stacking and electrostatic interactions between doxorubicin (DOX) and the carriers. These DOX-loaded nanogels showed rapid drug release under slightly acidic conditions. The cell and animal experiments confirmed that LACMC-NBA NPs increased cellular uptake, improved cytotoxicity in tumor cells, and enhanced growth inhibition in vivo than CMC-NBA NPs. Thus, these photo-crosslinked nanogels possess great potential for DOX delivery.