介孔硅固液相变性纳米粒复合物原位产氧产碱双重改善肿瘤微环境对肿瘤化疗增敏作用

肿瘤特殊的乏氧和酸性微环境是产生多药耐药和恶性进展的重要促成因素，通过氧供和碱化细胞外酸性微环境的策略可能提高肿瘤治疗响应性，对抗肿瘤多药耐药并抑制肿瘤浸润、转移。介孔硅包载相变性过氧化钙载药纳米粒复合物体系稳定性好、载药量大，聚焦超声刺激体系固液相变后，肿瘤局部区域快速释放出的CaO₂与肿瘤间质内富含的大量水分子反应生成足量 O₂ 的同时也生成碱类化合物Ca（OH）₂，维持时间长，从而通过肿瘤区域原位高效产氧、产碱，双重调节微环境而实现增敏化疗药物的作用。同时高原位产氧的特性可能具有局部超声增强显像潜能。该体系通过化学修饰携带肿瘤归巢穿膜肽，可靶向穿透肿瘤血管和间质，有利于进一步提高肿瘤内靶向递送效能。

Tumor hypoxic and acidic microenvironment significantly induce tumor multidrug-resistance and malignant process. Improving oxygen saturation and alkalifying extra-cellular acidic microenvironment may enhance the response of tumor therapy, which defense against multidrug resistance and suppress tumor infiltration as well as metastasis. Mesoporous silica-coated CaO₂ phase-change materials nanoparticle drug delivery system characterized by many a advantages of high stability, large drug loading, ect. More importantly, focused ultrasound phase-transformates the drug delivery system, CaO₂ is quickly released on tumor regions and reacts with H₂O, generating a large amount of O₂ and Ca（OH）₂ , which simultaneously regulates tumor microenvironment of hypoxia and acid so as to enhance tumor chemotherapy. As the same time, our drug delivery system has the potential for enhancing tumor imaging because of highly efficient oxygen generation in situ. Additionally，THPs-MONs-14-CaO₂NPs is modified with homing-penetrating peptide, which can specifically penetrate tumor blood vessels and tumor stroma, and further improve tumor targeting delivery efficacy.