Precise Delivery of Ricin A-Chain and Photosensitizer by Aptamer-Functionalized Liposome for Targeted Chemo-Photodynamic Synergistic Therapy

Abstract

Ricin, a potent protein synthesis inhibitor, shows significant potential as an anticancer agent. However, the limited delivery efficiency to tumor cells hampers its therapeutic efficacy. Here, we propose a novel approach for precise delivery of ricin A-chain (RTA) to tumors using aptamer-functionalized liposomes. RTA initially binds to Golgi-targeting carbon dots (CDs), followed by the encapsulation of CDs−RTA conjugates in aptamer-functionalized liposomes. Leveraging the precise recognition between nucleolin and aptamers and CDs' Golgi targeting, we achieve efficient transportation of RTA to tumor cells, thereby facilitating its potent chemotherapeutic effect. Furthermore, we enhanced the therapeutic efficacy by incorporating the photosensitizer pheophorbide a (PPa) into liposomes. Combined with near-infrared laser-mediated photodynamic therapy and chemotherapy, the liposomal system exhibits superior antitumor activity compared to monotherapy. This synergistic bimodal approach holds great promise for various biomedical applications, particularly in the field of cancer therapy.