Journal
SMALL
Volume 18, Issue 30, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202202337
Keywords
biomimetic nanoparticles; chemotherapy; homologous targeting; membrane coating; osteosarcoma; self-assembly
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81702661, 82072957, 51973112]
- Science Foundation of The Shanghai Municipal Science and Technology Commission [18JC1410800, 19JC1410300, 20ZR1434000]
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Inspired by the Watson-Crick base pairing in nucleic acids, hydrophobic and hydrophilic chemo-drugs are self-assembled into nanoparticles and coated with cancer cell membranes. These cancer-cell membrane-coated nanoparticles exhibit excellent stability, tumor-targeting capability, and inhibit the PI3K/AKT/mTOR pathway, promoting cancer cell apoptosis and cell cycle arrest. The cell membrane camouflage significantly prolongs the circulation half-life of nanoparticles, enhances drug accumulation at tumor sites, and improves anti-tumor efficacy.
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.
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