Multifunctional nanoagents integrating multiple therapeutic and imaging functions hold promise in the field of non-invasive and precise tumor therapies. However, the complex preparation process and uncertain drug metabolism of nanoagents loaded with various therapeutic agents or imaging agents greatly hinder its clinical applications. Developing simple and effective nanoagents that integrate multiple therapeutic and imaging functions remain a huge challenge. Therefore, a novel strategy based on in situ hydrogen release is proposed in this work: aminoborane (AB) was loaded onto mesoporous polydopamine nanoparticles (MPDA NPs) as a prodrug for hydrogen production, and then, PEG was modified on the surface of nanoparticles (represented as AB@MPDA-PEG). MPDA NPs not only act as photothermal agents (PTA) with high photothermal conversion efficiency (808 nm, η = 38.72%) but also as the carriers of AB accumulated in the tumor through enhanced permeability and retention (EPR) effect. H₂ gas generated by AB in the weak acid conditions of the tumor microenvironment (TME) not only was used to treat tumors via a combination of hydrogen and photothermal therapies but also serves as a US and CT contrast agent, providing accurate guidance for tumor treatment. Finally, in vivo and in vitro investigation suggest that the designed multifunctional nanosystem not only showed excellent properties such as high hydrogen-loading capacity, long-lasting sustained hydrogen release ability and excellent biocompatibility but also achieve selective PTT/hydrogen therapies and US/CT bimodal imaging functions, which can effectively guide antitumor therapies. The proposed hydrogen gas-based strategy for combination therapies and bimodal imaging integration holds promise as an efficient and safe tumor treatment for future clinical translation.

中文翻译：

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用于双峰成像引导的协同光热/氢疗法的原位氢纳米发电机

集成多种治疗和成像功能的多功能纳米药物在非侵入性和精确的肿瘤治疗领域大有可为。然而，载有各种治疗剂或显像剂的纳米制剂制备过程复杂，药物代谢不确定，极大地阻碍了其临床应用。开发集成多种治疗和成像功能的简单有效的纳米药物仍然是一个巨大的挑战。因此，一种基于原位的新策略在这项工作中提出了氢释放：将氨基硼烷 (AB) 负载到介孔聚多巴胺纳米颗粒 (MPDA NPs) 作为产氢前药，然后在纳米颗粒表面修饰 PEG（表示为 AB@MPDA-PEG）。MPDA NPs 不仅作为具有高光热转换效率（808 nm，η = 38.72%）的光热剂（PTA），而且作为通过增强渗透性和保留（EPR）效应在肿瘤中积累的 AB 的载体。AB在肿瘤微环境（TME）的弱酸性条件下产生的H ₂气体不仅可以通过氢气和光热疗法的组合治疗肿瘤，还可以作为US和CT造影剂，为肿瘤治疗提供准确指导. 最后，在体内和体外研究表明，所设计的多功能纳米系统不仅表现出优异的性能，例如高氢负载能力，长效的持续氢释放能力和优异的生物相容性，而且实现选择性PTT /氢疗法和US / CT双峰成像功能，可有效指导抗肿瘤治疗。提出的基于氢气的联合疗法和双峰成像集成策略有望成为未来临床转化的有效且安全的肿瘤治疗方法。