Mesenchymal stem cells loaded with paclitaxel&ndash;poly(lactic-<em>co</em>-glycolic acid) nanoparticles for glioma-targeting therapy

Abstract

BackgroundMesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.PurposeThe objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.MethodsPtx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.ResultsThe optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.ConclusionBased on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.

Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

“…Latest investigations have focused on the development of strategies to improve the payload and delivery capacity of MSCs. In this sense, nanoparticles are a promising approach to increase the anti-tumor efficacy of MSCs loaded with anti-cancer drugs (Layek et al, 2018;Wang et al, 2018;Moku et al, 2019). Drugencapsulated nanoparticles offer multiple therapeutic benefits by providing preferential accumulation at the target site, preventing burst release and reducing side effects.…”

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…In addition, mesenchymal stem cells have been shown to migrate to tumors in response to the secretion of various signaling molecules. Then, a smart strategy is to induce the internalization of drug-loaded nanoparticles within these cells to then delivering them specifically to tumor tissues [118][119][120][121].…”

Engineered Mesenchymal Stem Cells for Targeting Solid Tumors: Therapeutic Potential beyond Regenerative Therapy

“…To overcome these drawbacks, a number of groups including ours have started investigating nanoparticle (NP)-encapsulated forms of drugs, which can increase the drug-carrying capacity of MSCs. NPs not only conceal drug molecules from the efflux transporters but also limit their diffusional clearance (Sadhukha et al, 2014;Zhang et al, 2015;Layek et al, 2016Layek et al, , 2018Yao et al, 2017;Wang et al, 2018b;Moku et al, 2019). Table 2 summarizes the various studies that have reported engineering of MSCs with NPs for applications such as targeted tumor therapy, imaging, and cell tracking.…”