Prodrug-based strategy with a two-in-one liposome for Cerenkov-induced photodynamic therapy and chemotherapy.
Prodrug-based strategy with a two-in-one liposome for Cerenkov-induced photodynamic therapy and chemotherapy.
复制标题
DOI：
10.1016/j.jconrel.2023.10.036
复制
发表时间：
2023-10
期刊：
影响因子：
--
通讯作者：
Huihui Liu;Qing Wang;Jingru Guo;Kai Feng;Yiling Ruan;Zhihao Zhang;Xin Ji;Jigang Wang
中科院分区：
文献类型：
--
作者：
Huihui Liu;Qing Wang;Jingru Guo;Kai Feng;Yiling Ruan;Zhihao Zhang;Xin Ji;Jigang Wang
切伦科夫辐射诱导光动力治疗（CR-PDT）可以解决传统PDT穿透组织的局限性。然而，在循环过程中，放射性核素和光敏剂的共同递送可能在正常组织中引起持续的光毒性。5-氨基乙酰丙酸（ALA）是一种可在细胞内转化为光敏原卟啉IX （PpIX）的癌症选择性光敏剂，其副作用可忽略不计。然而，ALA的亲水性和PpIX向光活性血红素的进一步转化严重阻碍了ALA基PDT的治疗效果。在此，我们开发了一种89zr标记的，pH响应的ALA和青蒿素（ART）共载脂质体（89Zr-ALA-Liposome-ART），用于高选择性癌症治疗。89Zr可以作为内部激发源自激活PpIX治疗CR-PDT，光失活性的Heme可以激活ART的化疗效果。89zr - ala -脂质体- art在皮下4t1荷瘤Balb/c小鼠、acr - pdt和化疗中表现出良好的肿瘤抑制能力。与抗pd - l1联合，89zr - ala - liposomes - art可诱导较强的抗肿瘤免疫，抑制肿瘤复发。
Cerenkov radiation induced photodynamic therapy (CR-PDT) can tackle the tissue penetration limitation of traditional PDT. However, co-delivery of radionuclides and photosensitizer may cause continuous phototoxicity in normal tissues during the circulation. 5-aminolevulinic acid (ALA) which can intracellularly transform into photosensitive protoporphyrin IX (PpIX) is a cancer-selective photosensitizer with negligible side effect. However, the hydrophilic nature of ALA and the further conversion of PpIX to photoinactive Heme severely hinder the therapeutic benefits of ALA-based PDT. Herein, we developed an89Zr-labeled, pH responsive ALA and artemisinin (ART) co-loaded liposome (89Zr-ALA-Liposome-ART) for highly selective cancer therapy.89Zr can serve as the internal excitation source to self-activate PpIX for CR-PDT, and the photoinactive Heme can activate the chemotherapeutic effect of ART. The89Zr-ALA-Liposome-ART exhibited excellent tumor inhibition capability in subcutaneous 4T1-tumor-bearing Balb/c miceviaCR-PDT and chemotherapy. Combined with anti-PD-L1, the89Zr-ALA-Liposome-ART elicited strong antitumor immunity to against tumor recurrence.