Chitgupi Upendra, Qin Yiru, Ghosh Sanjana, Quinn Breandan, Carter Kevin, He Xuedan, Sunar Ulas, Lovell Jonathan F
Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
Pharmaceutics. 2023 Sep 26;15(10):2385. doi: 10.3390/pharmaceutics15102385.
Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery of chemotherapeutic drugs to tumor for cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand for targeted drug delivery, was used to decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed for FA-targeted chemophototherapy (CPT). PoP liposomes and FA-conjugated PoP liposomes were loaded with Doxorubicin (Dox), and physical properties were characterized. In vitro, FA-PoP liposomes that were incubated with FA receptor-overexpressing human KB cancer cells showed increased uptake compared to non-targeted PoP liposomes. Dox and PoP contributed towards chemophototherapy (CPT) in vitro, and PoP and FA-PoP liposomes induced cell killing. In vivo, mice bearing subcutaneous KB tumors treated with PoP or FA-PoP liposomes loaded with Dox, followed by 665 nm laser treatment, had delayed tumor growth and improved survival. Dox delivery to tumors increased following laser irradiation for both PoP and FA-PoP liposomes. Thus, while Dox-FA-PoP liposomes were effective following systemic administration and local light irradiation in this tumor model, the FA targeting moiety did not appear essential for anti-tumor responses.
光响应脂质体已被开发用于按需释放药物。然而，将化疗药物有效递送至肿瘤用于癌症诊疗仍然是一项挑战。在此，叶酸（FA）是一种用于靶向药物递送的既定配体，被用于修饰光敏卟啉 - 磷脂（PoP）脂质体，并对其进行FA靶向化学光动力疗法（CPT）评估。PoP脂质体和FA共轭PoP脂质体负载了阿霉素（Dox），并对其物理性质进行了表征。在体外，与过表达FA受体的人KB癌细胞孵育的FA - PoP脂质体相比于非靶向PoP脂质体显示出更高的摄取量。Dox和PoP在体外有助于化学光动力疗法（CPT），并且PoP和FA - PoP脂质体诱导细胞杀伤。在体内，用负载Dox的PoP或FA - PoP脂质体治疗皮下KB肿瘤小鼠，随后进行665 nm激光治疗，肿瘤生长延迟且生存期延长。对于PoP和FA - PoP脂质体，激光照射后肿瘤中的Dox递送均增加。因此，虽然在该肿瘤模型中全身给药和局部光照射后Dox - FA - PoP脂质体是有效的，但FA靶向部分对于抗肿瘤反应似乎并非必不可少。
