Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

• DOI: 10.1016/j.bioactmat.2022.06.013
• Publication Date: 2022-06-23T10:12:09Z
• Authors: Kangkang Ying; Yifeng Zhu; Jianqin Wan; Chenyue Zhan; Yuchen Wang; Binbin Xie; Peirong Xu; Hongming Pan; Hangxiang Wang
• Keywords: Camptothecin

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand strategies treat various diseases. Numerous synthetic nanoparticles have been developed pharmaceutical delivery cancer treatment. However, only a limited number nanotherapies enter clinical trials or are clinically approved. Systemically administered likely be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics insufficient drug concentrations tumors. Bioinspired drug-delivery formulations emerged as an alternative approach evade the MPS show potential improve therapeutic efficacy. Here we biodegradable polymer-conjugated camptothecin prodrug encapsulated plasma membrane lipopolysaccharide-stimulated macrophages. Polymer conjugation revived parent agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling encapsulation. Furthermore, macrophage cloaking transformed nonadhesive into bioadhesive nanocamptothecin, increasing cellular uptake tumor-tropic effects this biomimetic therapy. When tested preclinical murine model breast cancer, macrophage-camouflaged nanocamptothecin exhibited higher level tumor accumulation than uncoated nanoparticles. intravenous administration therapy effectively suppressed growth metastatic burden without causing systematic toxicity. Our study describes combinatorial strategy that uses polymeric design cell achieve therapeutics with high efficacy low This might also generally applicable formulate other candidates not compatible miscible carriers.