Pursuing Specific Chemotherapy of Orthotopic Breast Cancer with Lung Metastasis from Docking Nanoparticles Driven by Bioinspired Exosomes

• DOI: 10.1021/acs.nanolett.9b00824
• Publication Date: 2019-04-09T21:04:53Z
• Authors: Fei Xiong; Xiang Ling; Xing Chen; Jing Chen; Jiaxing Tan; Wuji Cao; Liang Ge; Minglin Ma; Jun Wu
• Keywords: 0303 health sciences; Lung Neoplasms; Breast Neoplasms; Serum Albumin, Human; Exosomes; 3. Good health; Mice; 03 medical and health sciences; Drug Delivery Systems; RAW 264.7 Cells; Animals; Humans; Nanoparticles; Female; Prodrugs; Laurates; Platinum

Breast cancer develops from local tissue but is characterized by a distinct metastatic pattern involving regional lymph nodes and distant organs, which the primary cause of high mortality in breast patients. Herein, optimal docking nanoparticles (NPs) composed laurate-functionalized Pt(IV) prodrug (Pt(lau)), human serum albumin (HSA), lecithin were predicted computational modeling, prepared nanoprecipitation, validated fluorescence spectroscopy. As macrophages have been reported to be preferentially recruited cancer, Rex, exosome spontaneously secreted murine RAW 264.7 cells, was isolated encapsulate NPs. This high-performance delivery system, called NPs/Rex, possessed desired physicochemical properties, enhanced colloidal stability, redox-triggered release profile. Investigations cytodynamics proved that NPs/Rex internalized through multiple pathways, avoided entrapment bilayers, successfully platinized nucleic acids after bioreduction cytosol. Intracellular activation Pt(lau) confirmed observing characteristic effects cisplatin on cell proliferation cycle following treatment with NPs/Rex. During vivo application, bioinspired Rex coating endowed NPs prolonged blood circulation, smart organ tropism, biocompatibility, as well robust platinum (Pt) chemotherapy for cells orthotopic tumors fat pads nodules lungs. Therefore, this favorable nanoplatform might provide valuable insight into derivatization development Pt anticancer drugs used currently clinic.