Evaluation of paclitaxel-loaded polymeric nanoparticles in 3D tumor model: impact of tumor stroma on penetration and efficacy

• DOI: 10.1007/s13346-023-01310-1
• Publication Date: 2023-02-28T14:02:50Z
• Authors: Dwi L. Priwitanin...; Kunal Pednekar; Alexandros V. Gab...; Aida A. Varela-Mo...; Severine Le Gac; Ivo Vellekoop; Gert Storm; Wim E. Hennink; Jai Prakash
• Keywords: Penetration (warfare)

Abstract Since tumor stroma poses as a barrier to achieve efficacy of nanomedicines, it is essential evaluate nano-chemotherapeutics in stroma-mimicking 3D models that reliably predict their behavior regarding these hurdles limiting efficacy. In this study, we evaluated the effect paclitaxel-loaded polymeric micelles (PTX-PMCs) and nanoparticles (PTX-PNPs) stroma–mimicking vitro model. PTX-PMCs (77 nm) based on amphiphilic block copolymer mPEG-b-p(HPMAm-Bz) PTX-PNPs (159 poly(lactic-co-glycolic acid) were prepared, which had an encapsulation efficiency (EE%) 81 ± 15% 45 8%, respectively. homospheroids mouse 4T1 breast cancer cells heterospheroids NIH3T3 fibroblasts (5:1 ratio) prepared characterized with high content two-photon microscopy immunostaining. Data showed induction epithelial-mesenchymal transition (α-SMA) both homo- heterospheroids, while ECM (collagen) deposition only heterospheroids. Two-photon imaging revealed fluorescently labeled PMCs PNPs penetrated into core Furthermore, PTX-PMCs, PTX-PNPs, free PTX induced cytotoxicity grown monolayer, but effects substantially reduced models, particular Gene expression analysis significant increase drug resistance markers (Bcl2, Abgc2) compared 2D or monocultures. Altogether, study shows nanotherapeutics challenged by stroma-induced poor penetration development resistant phenotype. Therefore, model can provide excellent platform before vivo studies. Graphical