Liposome-based anchoring and core-encapsulation for combinatorial cancer therapy

Downregulated pro-apoptotic protein in cancer cells compromises the chemotherapy by a cytotoxic drug. Here, we report co-delivery of a pro-apoptotic protein, caspase 3 (Cas 3), and cytotoxic agent, oridonin (ORD), for synergistic cancer treatment, using a method of liposome-based anchoring and core encapsulation. First, ORD is modified with hyaluronic acid (HA) to improve its solubility. Then, the targeted codelivery system is prepared by assembling the conjugate HA-ORD onto the Cas 3-loaded liposomes, which the surface HA can target the CD44 receptor on cancer cells. In vitro, the co-loaded liposomes (120nm) are specifically taken up by 4T1 cells and endow a 1.5-fold increase of Cas 3. After intravenous injection into the tumor-bearing mice, the liposomes accumulate in the tumor with high efficacy and significantly inhibit tumor growth via promoting apoptosis and anti-proliferation of cancer cells. Mechanistically, the co-delivery works synergistically by upregulating the activated Cas form, cleaved-Cas 3. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

In this study, a liposome-based co-delivery system was developed to simultaneously deliver pro-apoptotic protein and cytotoxic drug for synergistic cancer treatment. The system improved the solubility of the drug and achieved efficient drug delivery by targeting receptors on cancer cells. In vivo experiments demonstrated that the co-delivery system significantly inhibited tumor growth.