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Co-Delivery Polymeric Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles to Target Cancer Stem-Like Cells

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Cancer Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2777))

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Nanoparticle drug delivery has been promoted as an effective mode of delivering antineoplastic therapeutics. However, most nanoparticle designs fail to consider the multifaceted tumor microenvironment (TME) that produce pro-tumoral niches, which are often resistant to chemo- and targeted therapies. In order to target the chemoresistant cancer stem-like cells (CSCs) and their supportive TME, in this chapter we describe a nanoparticle-based targeted co-delivery that addresses the paracrine interactions between CSC and non-cancerous mesenchymal stem cells (MSCs) in the TME. Carcinoma-activated MSCs have been shown to increase the chemoresistance and metastasis of CSC. Yet their contributions to protect the CSC TME have not yet been systematically investigated in the design of nanoparticles for drug delivery. Therefore, we describe the fabrication of degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (120–200 nm), generated with an electrospraying process that encapsulates both a conventional chemotherapeutic, paclitaxel, and a targeted tyrosine kinase inhibitor, sunitinib, to limit MSC interactions with CSC. In the 3D hetero-spheroid model that comprises both CSCs and MSCs, the delivery of sunitinib as a free drug disrupted the MSC-protected CSC stemness and migration. Therefore, this chapter describes the co-delivery of paclitaxel and sunitinib via PLGA nanoparticles as a potential targeted therapy strategy for targeting CSCs. Overall, nanoparticles can provide an effective delivery platform for targeting CSCs and their TME together. Forthcoming studies can corroborate similar combined therapies with nanoparticles to improve the killing of CSC and chemoresistant cancer cells, thereby improving treatment efficiency.

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This work is supported primarily by the American Cancer Society Research Scholar Award RSG-19-003-01-CCE (G.M.), the Office of the Assistant Secretary of Defense for Health Affairs through the Ovarian Cancer Research Program, under award no. W81XWH-13-1-0134 (G.M.), W81XWH-16-1-0426 (G.M.), DOD Investigator Initiated award W81XWH-18-0346 (G.M.), Michigan Ovarian Cancer Alliance (G.M.), and NSF EFRI DChem (award number 2029139, G.M. A.T.). Research reported in this publication was supported by the National Cancer Institute under award number P30CA046592 and by the National Institutes of Health under grant number UL1TR002240.

Author Contributions

Conceptualization, G.M., A.T.; formal analysis, C.S.S., K.M.B., T.R., G.M., A.T.; writing–original draft preparation, C.S.S., K.M.B., T.R., G.M.; writing–review and editing, C.S.S., K.M.B., T.R., G.M., A.T.; supervision, G.M., A.T.; funding acquisition, G.M., A.T. All authors have read and agreed to this version of the manuscript.

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Correspondence to Geeta Mehta .

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© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Snyder, C.S., Repetto, T., Burkhard, K.M., Tuteja, A., Mehta, G. (2024). Co-Delivery Polymeric Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles to Target Cancer Stem-Like Cells. In: Papaccio, F., Papaccio, G. (eds) Cancer Stem Cells. Methods in Molecular Biology, vol 2777. Humana, New York, NY.

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  • Print ISBN: 978-1-0716-3729-6

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