NIR/pH-responsive Biomimetic Small Molecular Drug Co-assembly For Imaging-guided Combinational Chemo-photothermal Therapy

Compared to traditional carrier delivery systems,carrier-free small molecule nanodrug self-delivery systems based on single or multiple small molecules can achieve an optimal drug loading close to 100%,which can enhance the anti-cancer activity and be in favor of overcoming the serious hidden biosafety problems from traditional nanocarriers.More importantly,the preparation method of new small molecule self-delivery nanomedicine is simple and green,which is helpful for biomedicine transformation.Besides,inspired by the structure of natural cell membrane,taking advantage of the biological characteristics of different cells,introducing naturally occurring cell membranes on the surface of nanomedicines is an emerging strategy for cancer treatment in the field of biomedicine.It could endow nano-medicine carriers with advantages as excellent biocompatibility,lower immunogenicity,and low non-specific uptake rate of the reticuloendothelial system,while solving the disadvantages of traditional carrier materials.In addition,the realization of on-demand drug release by designing stimulus-response characteristics is also of great benefit in improving the application of biomimetic nanomedicines in the field of cancer treatment.Considering the drawbacks of carrier-free nanomedicine including the serious drug burst release,poor stability,and lacking of immune escape function,we fabricated a novel RBC membranes biomimetic combinational therapeutic system by enveloping the small molecular drug co-assemblies of chemo-drug 10-hydroxycamptothecin(10-HCPT)and near-infrared fluorescent probe indocyanine green(ICG)in the RBC membranes for prolonged circulation,controlled drug release,and synergistic chemo-photothermal therapy(PTT).The self-reorganized RBCs@ICG-HCPT nanoparticles(NPs)exhibited a diameter of～150 nm with core-shell structure,high drug payload,and reduced RES uptake function.Taking advantage of the stealth functionality of RBC membranes,RBCs@ICG-HCPT NPs remarkably enhanced the accumulation at the tumor sites via passive targeting followed by cellular endocytosis.Upon the stimuli of near-infrared(NIR)laser followed by acidic stimulation,RBCs@ICG-HCPT NPs showed a NIR/pH-responsive burst release effect by both heat-mediated membrane disruption and pH change.At the same time,the fluorescent dye ICG is used for in vivo fluorescence imaging and photothermal therapy.Consequently,the cell and animal level results demonstrated that compared with individual treatment,RBCs@ICG-HCPT NPs under dual-stimuli accomplished highly killing efficient in cancer cells.In vivo experiments results demonstrated remarkable ablation without recurrence of tumors by chemo-PTT combination therapy.This biomimetic nanoplatform based on carrier-free,small molecular drug co-assemblies integrating imaging capacity as a promising theranostic system provides potential for cancer diagnosis and combinational therapy.