Macrophage membrane-coated SN-38-encapsulated liposomes for efficient treatment of colorectal cancer
Xiaoyan Qi, Xuyang Hou, Zuxing Wei, Dekun Liu, Yin Sun, Yuhong Jiang, Chao Liu, Weihan Zhou, Leping Yang, Kuijie Liu
Abstract
SN-38, recognized as the primary active derivative of the pivotal chemotherapeutic agent CPT-11, demonstrates substantially enhanced efficacy in colorectal cancer (CRC) management compared to CPT-11. Nonetheless, challenges such as low stability, inadequate aqueous solubility, limited bioavailability, and non-specific targeting to cancer cells hinder its clinical adoption. In the present research, we synthesized SN-38-loaded liposomes cloaked with macrophage membranes (SN-38@MM-LPs) to assess their therapeutic potential and safety profile in addressing CRC. SN-38@MM-LPs were synthesized using an incubation extrusion technique, combining a macrophage membrane with liposomes (LPs). It was characterized by size, zeta potential, transmission electron microscopy observations, polydispersity index and coomassie bright blue staining. CCK-8, EdU, and flow cytometry assays were performed to evaluate the viability and apoptosis rates of HCT116 and HCT8 cells after treatment with SN-38@MM-LPs. A cellular uptake assay was conducted to evaluate the internalization of SN-38@MM-LPs in vitro. Moreover, the biodistribution, therapeutic efficacy, and safety of SN-38@MM-LPs were further assessed in orthotopic HCT116 xenograft model mice. Characterization results revealed that SN-38@MM-LPs possess a spherical morphology with a consistent size distribution (129 nm) and a drug loading efficiency of 5.54 ± 0.73%. SN-38 curtailed the growth and promoted apoptosis in both HCT8 and HCT116 cells. The impact of SN-38 was accentuated when delivered via SN-38@LPs and SN-38@MM-LPs. Notably, in the orthotopic xenograft model, SN-38@MM-LPs manifested superior tumor-targeting capabilities and therapeutic outcomes. Additionally, SN-38@MM-LPs presented negligible hepatic toxicity. SN-38@MM-LPs showcased potent and targeted antitumor actions in CRC. Consequently, SN-38@MM-LPs emerge as a potential nanoparticle formulation that could amplify the antitumor efficacy of SN-38, simultaneously mitigating liver toxicity concerns.