Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

摘要: Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) generate a tumor-associated antigen tumor microenvironment. Cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) were used enhance T helper (Th) 1 response. However, CpG ODNs also induced secretion interleukin-10 (IL-10) that reduces Th1 response and enhances 2 (Th2) Therefore, RNA interference downregulate IL-10 from bone marrow-derived den-dritic cells (BMDCs). For combined immunomodulation BMDCs, we fabricated two types poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing activate BMDCs via Toll-like receptor 9 ODN-encapsulated PLGA NPs, PCNs) small interfering silence (IL-10 RNA-encapsulated PINs). Treatment both NPs increased Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for effective induction an antitumor After primary injection HA/PTX complex, generated taken up by tumor-recruited BMDCs. secondary immunomodulating PCNs PINs, became activated migrated tumor-draining lymph nodes. As result, combination complex PINs not only efficiently inhibited but animal survival rate. Taken together, our results suggest sequential treatment chemotherapeutic agent immunomodulatory nanomaterials represents promising strategy efficient therapy.