A dual-prodrug nanoparticle based on chitosan oligosaccharide for enhanced tumor-targeted drug delivery

The premature leakage of chemotherapeutics during delivery impedes drugs from entering tumor cells, which produces considerable side effects in normal organs. Herein, we describe a hydrophobic-hydrophilic balanced self-assembled prodrug nanoparticle (HA-DOX@HA-CSO-g-OA), formed via a facile synthesis based on chitosan oligosaccharide to reduce the non-targeting risk of premature leakage of chemotherapeutics during their delivery. The HA-DOX@HA-CSO-g-OA have a suitable size (similar to 186 nm) with a doxorubicin (DOX) loading of 9.88% and an oleanolic acid (OA) loading efficiency of 27.34%. The release of DOX or OA is pH-dependent and responds particularly well to the acidic tumor microenvironment. In vitro antitumor activity studies revealed that HA-DOX@HA-CSO-g-OA had enhanced performance in promoting tumor apoptosis and displayed significant anticancer effects compared to mono-delivery. In vitro cell studies showed that HA-functionalized nanoparticles could enhance the cellular uptake in tumor cells. Therefore, HA-DOX@HA-CSO-g-OA is a promising vehicle for CD44-targeted co-delivery of cancer chemotherapy, which deserves further evaluation.