Facile encapsulation of hydroxycamptothecin nanocrystals into zein-based nanocomplexes for active targeting in drug delivery and cell imaging.

Nano-drug delivery systems that integrate inorganic and organic or even bioactive components into a single nanoscale platform are playing a hugely important role in cancer treatment. In this article, the fabrication of a versatile nanocarrier based on self-assembled structures of gold nanoparticles (AuNPs)-zein is reported, which displays high drug-loading efficiency for needle-shaped hydroxycamptothecin (HCPT) nanocrystals. The surface modification with folate-conjugated polydopamine (PFA) renders them stable and also facilitates their selective cellular internalization and enhancement of endocytosis. The release of payloads from nanocomplexes (NCs) was shown to be limited at physiological pH (17.1±2.8%) but significantly elevated at endosomal/lysosomal pH (58.4±3.0%) and at enzymatic environment (81.4±4.2%). Compared to free HCPT and its non-targeting equivalent, HCPT@AuNPs-Zein-PFA exerted a superior tumor suppression capacity as well as low side effects due to its active and passive targeting delivery both in vitro and in vivo. These results suggest that the NCs with well-defined core@shell nanostructures encapsulated with HCPT nanocrystals hold great promise to improve cancer therapy with high efficiency in the clinic. STATEMENT OF SIGNIFICANCE: A novel nanocomplex with HCPT nanocrystals encapsulated was designed to achieve selective cellular uptake by endocytosis, acid responsive release in the tumor microenvironment and excellent tumor suppression without toxicity. This nanocomplex with conjugation of folate was stable in the bloodstream, with minimal drug release in extracellular conditions, leading to prolonged blood circulation and high accumulation in tumor tissues. The entrapment of a nanocrystal drug into nanomaterials might be capable of delivering drugs in a predictable and controllable manner.