Abstract
BackgroundMulti-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells.ResultsCCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs.ConclusionsThis research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.Graphical
Highlights
Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community
paclitaxelbovine serum albumin (PTX-Bovine serum albumin (BSA))/BSA mixture was loaded on LDH-ICG NSs (LI) to make LIP NSs via adsorption through electrostatic interactions between the positively charged LI surface and negatively charged PTX-BSA/BSA molecules
After loading PTX-BSA/BSA and coating cancer cell membrane (CCM), laser irradiation compared with the corresponding group (LIPC) displayed a core–shell structure with the shell of 6–10 nm in length (Fig. 1C), which is in alignment with CCM-coated polymer and poly(lactic-coglycolic acid) nanoparticles [14, 30]
Summary
Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. Cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. The limited effectiveness of chemotherapy is mainly attributed to off-target of the anti-tumor agents, drug resistance, and severe side effects. As a non-invasive and local therapy modality, phototherapy addresses drug resistance, increases the efficacy of chemotherapy, and reduces associated side effects.
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