Chongqing Key Laboratory of Ultrasound Molecular Imaging, Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China.
Vascular Surgery Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China.
ACS Appl Mater Interfaces. 2021 Jan 27;13(3):3605-3621. doi: 10.1021/acsami.0c19259. Epub 2021 Jan 15.
Breast cancer is a major threat to health and lives of females. Biomimetic nanotechnology brought brighter hope for early diagnosis and treatment of breast cancer. Here, we proposed a platelet (PLT) membrane-derived strategy for enhanced photoacoustic (PA)/ultrasonic (US)/fluorescence (FL) multimodal imaging and augmented synergistic photothermal/chemotherapeutic efficacy in tumor cells. A PA imaging contrast and photothermal agent, nanocarbons (CNs), a chemotherapeutic and FL material, doxorubicin (DOX), and perfluoropentane (PFP) were coencapsulated into the poly(lactic--glycolic) acid (PLGA) skeletons. Then, the PLT membranes were coated onto the PLGA NPs, which were named as "nanoplatelets" (DOX-PFP-CNs@PLGA/PM NPs). The "nanoplatelets", which conserved the structural advantages and inherent properties of PLTs, could not only escape from phagocytosis of macrophages but also actively targeted tumor cells by the way of antigen-antibody interactions between P-selectin on the PM and CD44 receptors of the tumor cells. With CNs and DOX loaded in, these "nanoplatelets" could serve as an excellent contrast agent for PA/FL imaging. Under laser irradiation, the "nanoplatelets" could turn light energy into heat energy. The laser-triggered photothermal effect, on the one hand, could ablate the tumor cells immediately, and on the other hand, could initiate the optical droplet vaporization of PFP, which subsequently enhanced US imaging and promoted the discharge of encapsulated DOX from the "nanoplatelets" for remarkably strengthening photothermal therapeutic power in turn. In this work, as compared with the bare drug-loaded nanoparticles, the "nanoplatelets" exhibited much more accumulation in the tumor cells, demonstrating superior multimodal imaging capability and preferable synergistic therapeutic performance. In conclusion, the "nanoplatelets" could serve as contrast agents for US imaging and PA imaging to guide the therapy. What is more, the bioinspired PLT-derived, targeted, and nontoxic "nanoplatelets", which were exploited for multimodal PA/US/FL imaging-guided synergistic photothermal/chemo therapy, will be of great value to breast cancer theranostics in the days to come.
乳腺癌是女性健康和生命的主要威胁。仿生纳米技术为乳腺癌的早期诊断和治疗带来了更光明的希望。在这里，我们提出了一种基于血小板（PLT）膜的策略，用于增强超声（US）/荧光（FL）多模态成像，并增强肿瘤细胞的协同光热/化学治疗效果。将光声（PA）成像对比剂和光热剂纳米碳（CNs）、化疗药物阿霉素（DOX）和全氟戊烷（PFP）共包封到聚乳酸-羟基乙酸共聚物（PLGA）骨架中。然后，将 PLT 膜涂覆到 PLGA NPs 上，命名为“纳米血小板”（DOX-PFP-CNs@PLGA/PM NPs）。“纳米血小板”保留了 PLT 的结构优势和固有特性，不仅可以逃避巨噬细胞的吞噬作用，还可以通过 PM 上的 P-选择素与肿瘤细胞上的 CD44 受体之间的抗原-抗体相互作用主动靶向肿瘤细胞。由于负载了 CNs 和 DOX，这些“纳米血小板”可以作为 PA/FL 成像的优秀造影剂。在激光照射下，“纳米血小板”可以将光能转化为热能。激光触发的光热效应一方面可以立即消融肿瘤细胞，另一方面可以引发 PFP 的光液滴蒸发，从而增强 US 成像，并促进封装的 DOX 从“纳米血小板”中释放，从而显著增强光热治疗效果。在这项工作中，与裸载药纳米颗粒相比，“纳米血小板”在肿瘤细胞中的积累更多，表现出更好的多模态成像能力和更好的协同治疗效果。总之，“纳米血小板”可以作为 US 成像和 PA 成像的造影剂来指导治疗。更重要的是，基于仿生 PLT 衍生的、靶向的、无毒的“纳米血小板”，用于多模态 PA/US/FL 成像引导协同光热/化疗，将对未来乳腺癌的治疗具有重要价值。
