Efficient retention of drugs at tumor sites was always desirable to maximize therapeutic functions, yet the main concern is the dynamic blood clearance induced fast removal from localized lesion. Herein, a tumor microenvironment activated covalently conjugation (self- and proximal conjugation) of tyramine modified Pt nanoclusters (PCMT NPs) was constructed by in situ produced radical hooks, leading to efficient accumulation of PCMT NPs at tumor sites. Such accumulation further aggravated the oxidative stress and provoked autophagy of tumor cells via activating the caspase-3 pathway mediated massive apoptosis, thereby stimulating immunogenic cell death (ICD). As verified by in vivo results, the PCMT NPs effectively suppressed primary and distant tumor growth (with an inhibition rate of 99%) while eliciting immunotherapeutic responses. As such, a new paradigm for boosting drug retention was provided, which enabled specific tumor treatment with synergistic therapeutic outcomes.

中文翻译：

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纳米药物通过原位产生的自由基钩与增强的自噬和免疫疗法进行近端锚定


为了最大限度地提高治疗功能，始终希望将药物有效保留在肿瘤部位，但主要问题是动态血液清除诱导从局部病灶中快速去除。在此，通过原位产生的自由基钩构建酪胺修饰的 Pt 纳米簇 （PCMT NPs） 的肿瘤微环境激活共价共轭 （自近端共轭），导致 PCMT NPs 在肿瘤部位有效积累。这种积累进一步加剧了氧化应激，并通过激活 caspase-3 通路介导了大量细胞凋亡，从而刺激免疫原性细胞死亡 （ICD） 引发肿瘤细胞自噬。体内结果验证，PCMT NPs 有效抑制原发性和远处肿瘤生长 （抑制率为 99%），同时引发免疫治疗反应。因此，提供了一种提高药物保留率的新范式，使特异性肿瘤治疗具有协同治疗结果。