Polydopamine-Based Multifunctional Platform for Combined Photothermal Therapy, Chemotherapy, and Immunotherapy in Malignant Tumor Treatment
Polydopamine-Based Multifunctional Platform for Combined Photothermal Therapy, Chemotherapy, and Immunotherapy in Malignant Tumor Treatment
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基于聚多巴胺的恶性肿瘤光热疗法、化疗和免疫疗法联合治疗的多功能平台
DOI：
10.1021/acsabm.8b00718
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发表时间：
2019-02-18
影响因子：
4.7
通讯作者：
Chen, Zhipeng
中科院分区：
文献类型：
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作者：
Chen, Rui;Zhu, Chenqi;Chen, Zhipeng
我们设计了一种多功能平台，将抗癌药物DOX和抗TLR-7免疫佐剂咪喹莫特（R837）共载于光热治疗剂聚多巴胺纳米粒（PDANPs）上，制备了PDANPs/DOX&R837纳米粒，用于光热治疗、化疗和免疫治疗，以提高肿瘤的治疗效果。为了向恶性肿瘤的高递送，将叶酸配体-受体识别分子接枝到纳米颗粒表面以获得更高的细胞摄取效率。颗粒大小，。考察了FA-PDA/DOX&R837纳米粒的电位、形态、载药量和药物释放特性。评价了近红外（NIR）激光辐射下的抗肿瘤效果，我们的结果表明，三模式策略联合治疗对肿瘤的抑制明显上级单一模式治疗。热疗和DOX的协同毒性几乎完全消除了肿瘤，并且它们与R837一起进一步促进树突状细胞的成熟以诱导强烈的抗肿瘤免疫应答，使得肿瘤复发率显著低于没有R837的情况。该平台可作为一种潜在的靶向给药系统用于联合治疗癌症。
We designed a multifunctional platform by coloading DOX, an antitumor drug, and imiquimod (R837), an immune adjuvant against Toll-like-receptor-7 (TLR-7), onto polydopamine nanoparticles (PDANPs), a photothermal therapy (PTT) agent, to develop PDA/DOX&R837 NPs used as combined photothermal therapy, chemotherapy, and immunotherapy in order to enhance the cancer therapeutic effects. For a high delivery to malignant tumors, a folate ligand-receptor recognition molecule was grafted to the nanoparticle surface for a higher cellular uptake efficiency. The particle size,. potential, morphology, drug loading content, and drug release profiles of FA-PDA/DOX&R837 NPs were investigated. The antitumor effects under near-infrared (NIR) laser radiation were evaluated, and our results showed that a three-mode strategy combined therapy was significantly superior to single-mode therapy for tumor suppression. The synergetic toxicity of hyperthermia and DOX almost completely eliminated tumors, and together with R837, they further promoted the maturation of dendritic cells to induce a strong antitumor immune response, making tumor recurrence substantially lower than that without R837. This platform can be used as a potential targeted drug delivery system for combined cancer therapy.