HIFU对于前列腺癌疗效确切，但仍存在病灶消融不完全和周边正常组织易损伤等问题。项目组前期制备了PLGA微球诊疗剂，具备一定的HIFU增效性能，但该类有机增效剂存在粒径大、结构不稳定和制备过程复杂等缺点，限制了其成像及增效效果。为了解决上述问题，本研究提出了采用简单可控的乳化聚合方法，制备粒径小和结构稳定的有机无机杂化（Hybrid-）纳米诊疗剂的思路。该诊疗剂表面镶嵌超顺磁纳米颗粒，内核负载乙酸异戊酯，将实现MRI示踪和HIFU治疗增效双重性能。进一步对诊疗剂表面链接特异性识别PSMA的J591单抗，将有效提高前列腺癌的靶向疗效。本项目将开展PSMA靶向Hybrid-SiO2基纳米诊疗剂的可控合成和结构表征，通过动物模型系统地评价诊疗剂的体内分布、安全性、示踪成像和HIFU增效等性能，并对其主动靶向和增效机制进行研究。本项目的开展将对HIFU增效剂的研究提供更加完善的理论基础和实验证据。

High intensity focused ultrasound (HIFU) is a type of clinical therapy that has been used for the ablation of localized prostate tumor, however, it generally leads to unsatisfactory ablation effect for the deep tumor as result of low energy deposition. In the previous research, a poly (lactic-co-glycolic acid) (PLGA) microsphere-based HIFU synergistic agent was fabricated by our group to significantly enhance the HIFU therapeutic efficacy. However, this organic agent still suffers from several problems including over-large particle size, rapid structural collapse and complex synthetic process, which limit its clinical translation. To solve the above problems, we propose to design a novel organic-inorganic silica (Hybrid-SiO2) nanosystem in this project, which possesses both HIFU synergistic liquid in the hollow cavity and plenty of superparamagnetic nanodots on the particle surface. Furthermore, the J591 antibody is chemically linked to the Hybrid-SiO2 nanosystem for the biological recognition of PSMA antigen in order to realize the positive targeting therapy for the prostate cancer. Thus, the designed nanosystem is a single multifunctional platform with HIFU ablation enhancement, magnetic resonance (MR) imaging and prostate cancer targeting capabilities, which is ideally feasible to be applied in MRI-guided HIFU therapy of prostate cancer. The effectiveness of the PSMA-targeting Hybrid-SiO2 nanosystem on theranostic application and tumor-specific recognition will be systemically evaluated in vitro, ex vivo and in vivo. Overall, this research will provide sufficient theoretic and experimental basis for the future study of HIFU synergistic therapy.