越来越多的证据表明，癌症干细胞（CSC）的存在是当前肿瘤治疗的主要挑战，特别是从非CSC向CSC分化的转变，以逃避常规治疗并驱动转移。在这里，我们提出了协同分化疗法和光疗的治疗策略，通过分化诱导剂诱导CSC分化为成熟肿瘤细胞，并通过光疗协同消除它们和正常癌细胞。在这项工作中，我们通过生物矿化合成了负载 IR-780 和全反式视黄酸 (ATRA) 的仿生纳米平台。该方法可以将铝离子整合到小尺寸的蛋白质载体中形成纳米团簇，该纳米团簇在酸性条件下发生响应性降解并促进肿瘤的深度渗透。在 ATRA 诱导的 CSC 分化的帮助下，IR-780 通过协同产生高热和活性氧来抑制 CSC 的自我更新和癌症进展。此外，ATRA可以促进光疗诱导的免疫原性细胞死亡，从而强烈引起全身抗肿瘤免疫反应，有效消除CSC和肿瘤细胞。总而言之，这种双重策略代表了通过诱导 CSC 分化、改善光热疗法/光动力疗法和增强抗肿瘤免疫力来靶向消灭 CSC 和肿瘤的新范例。© 2023 沉阳药科大学。由 Elsevier B.V. 出版

Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.© 2023 Shenyang Pharmaceutical University. Published by Elsevier B.V.