Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Mater. 2023 Jul;35(28):e2300048. doi: 10.1002/adma.202300048. Epub 2023 May 25.
Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial-temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo-conjugated-polymer is designed via Stille polymerization, resulting in PSP-Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR-II light. PSP-Pt can co-assemble with a commercially available lipid polymer, namely mPEG -DSPE, into NP . Under 1064 nm light irradiation, NP can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo-immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR-II light for accelerating Pt(IV) reduction for cancer tumor therapy.
肿瘤内选择性激活 Pt(IV)前药特别有吸引力，因为它们对正常组织的损伤较小。然而，目前通过化学/光还原将 Pt(IV)前药转化为 Pt(II)前药的常用方法受到这种还原过程不理想的时空控制以及不理想的光的组织穿透深度的限制。在这里，通过 Stille 聚合设计了一种伪共轭聚合物，得到了具有奥沙利铂（Oxa(IV)）Pt(IV)前药的 PSP-Pt，该前药可以被近红外二区 (NIR-II) 光激活。PSP-Pt 可以与市售的脂质聚合物，即 mPEG-DSPE，共组装成 NP。在 1064nm 光照射下，NP 可以被光激活，加速 Pt(IV)还原，从而通过光热效应和化学免疫疗法杀死 CT26 结肠癌小鼠模型中的癌细胞。这项工作报道了近红外二区光在加速 Pt(IV)还原以用于癌症肿瘤治疗中的应用。
