DNA Base Pairing‐Inspired Supramolecular Nanodrug Camouflaged by Cancer‐Cell Membrane for Osteosarcoma Treatment. Issue 30 (3rd July 2022)

• Record Type: Journal Article
• Authors: Fu, Yucheng; He, Guoyu; Liu, Zhuochao; Wang, Jun; Li, Meng; Zhang, Zhusheng; Bao, Qiyuan; Wen, Junxiang; Zhu, Xinyuan; Zhang, Chuan; Zhang, Weibin
• Is Part Of: Small. Volume 18:Issue 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-03
• Subjects: biomimetic nanoparticles -- chemotherapy -- homologous targeting -- membrane coating -- osteosarcoma -- self‐assembly; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202202337
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Osteosarcoma (OS) is one of the most common bone malignant tumors which mainly develops in adolescents. Although neoadjuvant chemotherapy has improved the prognosis of patients, numerous chemotherapeutic challenges still limit their use. Here, inspired by the Watson–Crick base pairing in nucleic acids, hydrophobic (methotrexate) and hydrophilic (floxuridine) chemo‐drugs are mixed and self‐assembled into M:F nanoparticles (M:F NPs) through molecular recognition. Then, the obtained NPs are co‐extruded with membranes derived from OS cells to form cancer‐cell membrane‐coated NPs (CCNPs). With protected membranes at the outer layer, CCNPs are highly stable in both physiological and weak acid tumor conditions and possess homologous tumor targeted capability. Furthermore, the proteomic analysis first identifies over 400 proteins reserved in CCNPs, most of them participating in tumor cell targeting and adhesion processes. In vitro studies reveal that CCNPs significantly inhibit the PI3K/AKT/mTOR pathway, which promotes cell apoptosis and cell cycle arrest. More importantly, cell membrane camouflage significantly prolongs the circulation half‐life of CCNPs, elevates the drug accumulation at tumor sites, and promotes anti‐tumor efficacy in vivo. As a convenient and effective strategy to construct a biomimetic NP with high drug loading ratio, the CCNPs provide new potentials for precise and synergistic antitumor treatment. Abstract : A DNA base pairing‐inspired supramolecular nanodrug is constructed through self‐assembly of two common chemodrugs and then camouflaged by cancer cell‐derived membranes to form cancer‐cell membrane coated nanoparticles (CCNPs). The CCNPs show high drug loading ratio, enhanced stabilities, excellent homologous targeting abilities, and prominent antitumor effect both in vitro and in vivo, which provides a new potential for cancer therapy.