Targeted delivery and stimulus-responsive release of anticancer drugs for efficient chemotherapy

Chemotherapy is currently an irreplaceable strategy for cancer treatment. Doxorubicin hydrochloride (DOX) is a clinical first-line drug for cancer chemotherapy. While its efficacy for cancer treatment is greatly compromised due to invalid enrichment or serious side effects. To increase the content of intracellular targets and boost the antitumor effect of DOX, a novel biotinylated hyaluronic acid-guided dual-functionalized CaCO₃-based drug delivery system (DOX@BHNP) with target specificity and acid-triggered drug-releasing capability was synthesized. The ability of the drug delivery system on enriching DOX in mitochondria and nucleus, which further cause significant tumor inhibition, were investigated to provide a more comprehensive understanding of this CaCO₃-based drug delivery system. After targeted endocytosis by tumor cells, DOX could release faster in the weakly acidic lysosome, and further enrich in mitochondria and nucleus, which cause mitochondrial destruction and nuclear DNA leakage, and result in cell cycle arrest and cell apoptosis. Virtually, an effective tumor inhibition was observed in vitro and in vivo. More importantly, the batch-to-batch variation of DOX loading level in the DOX@BHNP system is negligible, and no obvious histological changes in the main organs were observed, indicating the promising application of this functionalized drug delivery system in cancer treatment.