Wu Jianrong, Williams Gareth R, Niu Shiwei, Gao Feng, Tang Ranran, Zhu Li-Min
College of Chemistry, Chemical Engineering and Biotechnology Donghua University Shanghai 201620 P. R. China.
UCL School of Pharmacy University College London 29-39 Brunswick Square London WC1N 1AX UK.
Adv Sci (Weinh). 2019 May 21;6(14):1802001. doi: 10.1002/advs.201802001. eCollection 2019 Jul 17.
Theranostic formulations, integrating both diagnostic and therapeutic functions into a single platform, hold great potential for precision medicines. In this work, a biodegradable theranostic based on hollow mesoporous organosilica nanoparticles (HMONs) is reported and explored for ultrasound/photoacoustic dual-modality imaging guided chemo-photothermal therapy of cancer. The HMONs prepared are endowed with glutathione-responsive biodegradation behavior by incorporating disulfide bonds into their framework. The nanoparticles are loaded with indocyanine green (ICG) and perfluoropentane (PFP). The former acts as a photothermal agent and the latter can generate bubbles for ultrasound imaging. A paclitaxel prodrug is developed to both serve as a redox-sensitive gatekeeper controlling ICG release from the HMON pores and a chemotherapeutic. ICG generates mild hyperthermia upon exposure to an 808 nm laser, and this in turn leads to a liquid-gas phase transition of PFP, resulting in the generation of bubbles which can be used for ultrasound imaging. The platform is found to have excellent properties for both ultrasound and photoacoustic imaging. In addition, both in vitro and in vivo results show that the nanoparticles provide potent synergistic chemo-photothermal therapy. The material developed in this work thus has great potential for exploitation in advanced cancer therapies.
治疗诊断制剂将诊断和治疗功能整合到一个单一平台，在精准医学方面具有巨大潜力。在这项工作中，报道并探索了一种基于中空介孔有机硅纳米颗粒（HMONs）的可生物降解治疗诊断制剂，用于超声/光声双模态成像引导的癌症化学-光热治疗。通过将二硫键引入其骨架，制备的HMONs具有谷胱甘肽响应性生物降解行为。纳米颗粒负载了吲哚菁绿（ICG）和全氟戊烷（PFP）。前者作为光热剂，后者可产生用于超声成像的气泡。开发了一种紫杉醇前药，既作为控制ICG从HMON孔中释放的氧化还原敏感守门人，又作为化疗药物。ICG在暴露于808 nm激光时产生温和的热疗，这反过来又导致PFP的液-气相转变，从而产生可用于超声成像的气泡。发现该平台在超声和光声成像方面均具有优异的性能。此外，体外和体内结果均表明，纳米颗粒提供了有效的协同化学-光热治疗。因此，这项工作中开发的材料在先进癌症治疗中具有巨大的开发潜力。
