Chemotherapy is widely used in combination with high-intensity focused ultrasound (HIFU) ablation for
cancer therapy; however, the spatial and temporal integration of
chemotherapy and HIFU ablation remains a challenge. Here, temperature-sensitive plateletsomes (TSPs) composed of platelet (PLT) membrane,
1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine and
1,2-dipalmitoyl-sn-glycero-3-phosphocholine were developed to adequately integrate
chemotherapy with HIFU
tumor ablation in vivo. Methods: The thermosensitive permeability of TSPs was evaluated under both water bath heating and HIFU
hyperthermia. The targeting performance, pharmacokinetic behavior and therapeutic potential of TSPs in combination with HIFU ablation were evaluated using HeLa cells and a HeLa cell
tumor-bearing nude mouse model in comparison with temperature-sensitive
liposomes (TSLs). Results: TSPs showed high drug loading efficiency and temperature-sensitive permeability. When applied in vivo, TSPs showed a circulation lifetime comparable to that of TSLs and exhibited PLT-specific
cancer cell affinity and a vascular damage response. Upon HIFU
hyperthermia, TSPs displayed ultrafast drug release and enhanced
tumor uptake, providing high drug availability in the
tumor site to cooperate with HIFU ablation. After HIFU ablation, TSPs rapidly targeted the postoperative
tumor site by adhesion to the damaged
tumor vasculature, leading to targeted and localized postoperative
chemotherapy. Conclusion: Due to effective integration at both intraoperative and postoperative stages, TSPs could be a promising
chemotherapy nanoplatform in combination with HIFU ablation for
cancer therapy.