Abstract
Chemotherapy research highly prioritized overcoming the multi-drug resistance (MDR) effect in cancer cells. It might occur through different mechanisms, but it correlated with the over expression of integral membrane transporters, such as P-glycoprotein (P-gp), and exhibited a lower nitric oxide production, with resulting decrease of drug accumulation and cellular death. Irinotecan hydrochloride (CPT-11) was a general anti-microtubule drug used to treat cancer. It was also the drug efflux mediated by P-glycoprotein (P-gp) transporters. We supposed that supplying enough amount of nitride oxide that reduced the overexpression of P-gp. Thus, the resistance to CPT-11 could be reversed when MCF-7/ADR cells were incubated with nitric oxide. To solve above problem, we developed pH-responsive nitric oxide releasing poly (D,L-lactic-co-glycolic acid) hollow microparticles (PLGA HMs). Organic shell used PLGA and their aqueous core carried CPT-11, polyvinyl alcohol (PVA) and DETA-NONOate, a gas-generating agent when presented in acidic environments. SEM morphology and drug release profile provided visible evidences of the acid-responsive release of CPT-11 from PLGA HMs. MTT assay showed that our PLGA HMs could release nitric oxide in acid experiment and released nitric oxide to enhance the toxicity of CPT-11 to MCF-7/ADR cells, bringing about more MCF-7/ADR cells death. Furthermore, we created an animal model in order to proving that our PLGA HMs had greater effects on treating MCF-7/ADR tumor tissue. The results suggested that the developed PLGA HMs that could release nitric oxide to inhibit P-glycoprotein expression and reduced drug efflux in MDR cells and was a highly promising approach in chemotherapy.