Zhu Bengao, Qu Fei, Bi Duohang, Geng Rui, Chen Senbin, Zhu Jintao
State Key Laboratory of Materials Processing and Mold Technology, and Key Laboratory of Materials Chemistry for Energy Conversion and Storage of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, Hubei 430074, China.
ACS Appl Mater Interfaces. 2023 Feb 8. doi: 10.1021/acsami.2c22338.
Tumor recurrence and metastasis are the main causes of cancer mortality; traditional chemotherapeutic drugs have severe toxicity and side effects in cancer treatment. To overcome these issues, here, we present a pH-responsive, self-destructive intelligent nanoplatform for magnetic resonance/fluorescence dual-mode image-guided mitochondrial membrane potential damage (MMPD)/photodynamic (PDT)/photothermal (PTT)/immunotherapy for breast cancer treatment with external near infrared (NIR) light irradiation. To do so, we construct multifunctional monolayer-layered double hydroxide (LDH) nanosheets (MICaP), co-loading indocyanine green (ICG) with ultrahigh loading content realized via electrostatic interactions, and calcium phosphate (Ca(PO)) coating via biomineralization. Such a combined therapy design is featured by the outstanding biocompatibility and provokes immunogenic cell death (ICD) of tumors toward cancer immunotherapy. The active transport of excess Ca released from pH-sensitive Ca(PO) can induce MMPD of tumor cells to minimize oxygen consumption in the tumor microenvironment (TME). The presence of ICG not only generates singlet oxygen (O) to induce apoptosis by photodynamic therapy (PDT) but also initiates tumor cell necrosis by photothermal therapy (PTT) under near-infrared (NIR) light radiation. Eventually, the immune response generated by MMPD/PDT/PTT greatly promotes a cytotoxic T lymphocyte (CTL) response that can limit tumor growth and metastasis. Both in vitro and in vivo studies indeed illustrate outstanding antitumor efficiency and outcomes. We anticipate that such precisely designed nanoformulations can contribute in a useful and advantageous way that is conducive to explore novel nanomedicines with notable values in antitumor therapy.
肿瘤复发和转移是癌症死亡的主要原因；传统化疗药物在癌症治疗中具有严重的毒性和副作用。为了克服这些问题，在此，我们提出了一种pH响应性、自毁型智能纳米平台，用于在外部近红外（NIR）光照射下进行磁共振/荧光双模式图像引导的线粒体膜电位损伤（MMPD）/光动力（PDT）/光热（PTT）/免疫疗法来治疗乳腺癌。为此，我们构建了多功能单层层状双氢氧化物（LDH）纳米片（MICaP），通过静电相互作用实现超高负载量地共负载吲哚菁绿（ICG），并通过生物矿化进行磷酸钙（Ca(PO)）包覆。这种联合治疗设计具有出色的生物相容性，并引发肿瘤的免疫原性细胞死亡（ICD）以用于癌症免疫治疗。从pH敏感的Ca(PO)释放的过量Ca的主动转运可诱导肿瘤细胞的MMPD，以最小化肿瘤微环境（TME）中的氧消耗。ICG的存在不仅通过光动力疗法（PDT）产生单线态氧（O）来诱导细胞凋亡，还在近红外（NIR）光辐射下通过光热疗法（PTT）引发肿瘤细胞坏死。最终，由MMPD/PDT/PTT产生的免疫反应极大地促进了细胞毒性T淋巴细胞（CTL）反应，从而可以限制肿瘤的生长和转移。体外和体内研究确实都表明了出色的抗肿瘤效率和效果。我们预计，这种精确设计的纳米制剂可以以有用且有利的方式做出贡献，有助于探索在抗肿瘤治疗中具有显著价值的新型纳米药物。
