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

Abstract

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

Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy

“…[3,4] The delivery of anticancer agents using nanocarriers is a popular research topic at present, and nanocarriers improve the bioavailability of anticancer agents, realizes timed/controlled release of these agents, and decreases DOI: 10.1002/adhm.202000605 their toxicity and side effects. [5,6] The passive targeting effect of nanocarriers in solid tumors is attributed to the combination of the enhanced permeability retention (EPR) effect and nanoscale (Figure 1). EPR effect refers to the nature that some molecules or particles tend to aggregate in tumor tissues compared with healthy tissues.…”

Mesenchymal Stem Cells-Derived Exosomes as Dexamethasone Delivery Vehicles for Autoimmune Hepatitis Therapy

“…Exosome is a promising drug carrier with different properties according to its parental cells. As a vehicle, Exo has already been widely used in the treatment of cancers (Li and Nabet, 2019), including glioblastoma (Zhu et al, 2019), pancreatic cancer (Li et al, 2020), and breast cancer with lung metastasis (Xiong et al, 2019). All treatments exhibited effective inhibition in tumor volume and curative effect on the survival time of tumor-bearing mice.…”

Engineered Extracellular Vesicles for Cancer Therapy

“…have designed bioinspired EVs that could encapsulate Pt anti‐cancer drugs for the therapy of orthotopic breast cancer with lung metastasis. [ 125 ] Taken together, these findings suggest that the use of bioinspired or biomimetic EVs to deliver chemotherapeutic drugs further expands the applicability of EVs in cancer therapy and achieves promising therapeutic effects in primary, metastatic, and drug‐resistant cancers.…”