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

Catherine S Snyder; Taylor Repetto; Kathleen M Burkhard; Anish Tuteja; Geeta Mehta

doi:10.1007/978-1-0716-3730-2_14

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

Methods Mol Biol. 2024:2777:191-204. doi: 10.1007/978-1-0716-3730-2_14.

Authors

Catherine S Snyder¹, Taylor Repetto¹, Kathleen M Burkhard², Anish Tuteja^{1

3

4

5}, Geeta Mehta^{6

7

8

9

10}

Affiliations

¹ Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
² Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
³ Macromolecular Sciences and Engineering, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁵ Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, USA. mehtagee@umich.edu.
⁷ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. mehtagee@umich.edu.
⁸ Macromolecular Sciences and Engineering, University of Michigan, Ann Arbor, MI, USA. mehtagee@umich.edu.
⁹ Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. mehtagee@umich.edu.
¹⁰ Precision Health, University of Michigan, Ann Arbor, MI, USA. mehtagee@umich.edu.

PMID: 38478345
DOI: 10.1007/978-1-0716-3730-2_14

Abstract

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.

Keywords: Cancer stem cells; Co-delivery; Degradable; Electrospray; Mesenchymal stem cells; Nanoparticle drug delivery; PLGA; Paclitaxel; Stromal cells; Sunitinib.

MeSH terms

Antineoplastic Agents* / pharmacology
Cell Line, Tumor
Drug Carriers
Glycols
Lactic Acid
Nanoparticles*
Neoplasms* / drug therapy
Paclitaxel / pharmacology
Polyglycolic Acid
Polylactic Acid-Polyglycolic Acid Copolymer
Sunitinib / pharmacology

Substances

Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Glycols
Sunitinib
Lactic Acid
Antineoplastic Agents
Paclitaxel
Drug Carriers