Development of Exosome-encapsulated Paclitaxel to Overcome MDR in Cancer cells
By M. Kim, Matthew J. Haney, Yuling Zhao, V. Mahajan, I. Deygen, N. Klyachko, Eli Inskoe, A. Piroyan, Marina Sokolsky, Onyi Okolie and 3 more. Nanomedicine: Nanotechnology, Biology and Medicine, 2015
1,359 citations recorded by the source corpus.
Exosomes have recently come into focus as “natural nanoparticles” for use as drug delivery vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we developed and compared different methods of loading exosomes released by macrophages with PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our studies demonstrated a nearly complete co-localization of airway-delivered exosomes with cancer cells in a model of murine Lewis Lung Carcinoma pulmonary metastases, and a potent anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers.
Subfields: Molecular Biology, Pharmaceutical Science, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/e44a25a43abfb41481b8ddd71bb67f4e9846b383
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Citations in the corpus
- Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “Similarly, increased neoplastic tropism and cytotoxicity is observed in MDR pulmonary metastases after treatment with macrophage EV-encapsulated paclitaxel [278].”
- Clinical applications of stem cell-derived exosomes (2024, methodology): “48 Ohno et al. loaded antitumor let-7a miRNA in HEK293-derived exosomes using transfection to manage breast cancer.”
- Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications (2020, neutral): “Kim et al.(32) compared the loading rates of the”
- Engineering exosomes for targeted drug delivery (2021, background): “Exosome-mediated delivery bypasses the P-glycoprotein drug efflux system, which can reduce drug resistance [18].”