Tailoring Multifunctional Small Molecular Photosensitizers to In Vivo Self-Assemble with Albumin to Boost Tumor-Preferential Accumulation, NIR Imaging, and Photodynamic/Photothermal/Immunotherapy
Tailoring Multifunctional Small Molecular Photosensitizers to In Vivo Self-Assemble with Albumin to Boost Tumor-Preferential Accumulation, NIR Imaging, and Photodynamic/Photothermal/Immunotherapy
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DOI：
10.1002/smll.202201298
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发表时间：
2022-06-02
期刊：
影响因子：
13.3
通讯作者：
Yu, Songtao
中科院分区：
文献类型：
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作者：
Luo, Shenglin;Luo, Xi;Yu, Songtao
癌症免疫疗法在根除肿瘤和抑制转移方面具有巨大潜力。然而，免疫佐剂的全身给药和癌症治疗的特异性不足，导致临床环境中的治疗效果有限和潜在的免疫相关副作用。在本报告中，优化了各种长度的七次甲基花青小分子的合成，作为多功能光敏剂（PS），用于肿瘤特异性积累、近红外（NIR）荧光成像和光动力/光热/免疫治疗。特别是，研究证明，在两个 N-烷基侧链上含有 8 个碳的 C8 可以与白蛋白有效自组装，形成纳米尺寸的染料-白蛋白复合物。这一特性有利于C8体内自组装，显着提高其水溶性、近红外荧光发射、长期血液循环以及肿瘤特异性积累。更重要的是，C8不仅对原发性肿瘤表现出优异的光疗效果，而且还能引发损伤相关分子模式的分泌、细胞因子的分泌、树突状细胞的成熟和细胞毒性T淋巴细胞的激活，最终引发足够的抗肿瘤免疫反应，抑制远处和转移性肿瘤的生长。因此，这种多功能小分子PS具有优异的肿瘤优先积累、成像引导激光照射和光疗诱导的原位抗肿瘤免疫反应的特点，为其在肿瘤靶向免疫治疗中的应用提供了广阔的前景。
Cancer immunotherapy has great potential in tumor eradication and metastasis suppression. However, systemic administration of immune adjuvants and inadequate specificity in cancer treatment, lead to restricted therapeutic benefits and potential immune-related side effects in clinical settings. In this report, the synthesis of various lengths of heptamethine cyanine small molecules to act as multifunctional photosensitizers (PS) for tumor-specific accumulation, near-infrared (NIR) fluorescent imaging, and photodynamic/photothermal/immunotherapy is optimized. In particular, it is demonstrated that C8, which contains eight carbons on two N-alkyl side chains, efficiently self-assembles with albumin to form nanosized dye-albumin complexes. This feature facilitates C8 in vivo self-assembly to remarkably improve its water-solubility, NIR fluorescent emission, long-term blood circulation, as well as tumor-specific accumulation. More importantly, C8 not only exhibits a superior phototherapeutic effect on primary tumors, but also elicits secretion of damage associated molecular patterns, cytokine secretion, dendritic cell maturation, and cytotoxic T lymphocytes activation, ultimately triggering a sufficient antitumor immune response to suppress growths of distant and metastatic tumors. Hence, this multifunctional small molecular PS is characterized with excellent tumor-preferential accumulation, imaging-guided laser irradiation, and phototherapy-induced in situ antitumor immune response, providing a prospective future of its use in tumor-targeting immunotherapy.