Co-delivery of nitric oxide and camptothecin using organic-inorganic composite colloidal particles for enhanced anticancer activity

Camptothecin (CPT) is a highly potent anticancer agent with low water solubility and high toxicity. Nitric oxide (NO) is a gaseous free-radical molecule with potential to enhance anticancer chemotherapy. In this study, we designed and fabricated hybrid colloidal particle carriers for simultaneous delivery of CPT and NO, aiming to produce augmented anticancer activities. The drug carrier contains two separate domains, where CPT is physically loaded in the PLGA particle and NO is chemically conjugated to the organosilica scaffold via S-nitrosothiol linkage. The fabrication involves preparation of CPT-loaded PLGA particles and deposition of S-nitroso-orga-nosilica, leading to the formation of anisotropic, Janus-like colloidal particles. We prepared and characterized 3 formulations with various entrapment amounts of CPT and NO (CPT:NO molar ratio = 1:4, 1:15, and 1:200). The release study demonstrates successful co-delivery of CPT and NO. Moreover, the formulations show increased cytotoxicity with increasing NO loading against various cancer cell lines. In conclusion, our study demonstrates the feasibility of co-delivering CPT and NO using organic-inorganic composite particle carriers. The hybrid nanocarriers increase the versatility of colloidal anticancer drug delivery.