ArticleDrug delivery and translational research2023
Evaluation of paclitaxel-loaded polymeric nanoparticles in 3D tumor model: impact of tumor stroma on penetration and efficacy.
Article in Drug delivery and translational research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Mesenchymal Stem Cell-Derived Exosomes Reprogram Chemosensitivity Pathways in Cervical Cancer Spheroids.International journal of molecular sciences · 2026Article
- Tumor-on-chip's alliance with molecular pathology against metastatic disease.Journal of biomedical science · 2026Review
- Nanoparticle Detection in Biology and Medicine: A Review.Biosensors · 2025Review
- From Spheroids to Tumor-on-a-Chip for Cancer Modeling and Therapeutic Testing.Micromachines · 2025Review
- Synergistic anticancer activity of resveratrol-loaded polymeric nanoparticles and sunitinib in colorectal cancer treatment.Royal Society open science · 2025Article
- A polysaccharide-based hydrogel platform for tumor spheroid production and anticancer drug screening.Scientific reports · 2025Article
- Harnessing 3D cell models and high-resolution imaging to unveil the mechanisms of nanoparticle-mediated drug delivery.Frontiers in bioengineering and biotechnology · 2025Review
- Architectural organization and molecular profiling of 3D cancer heterospheroids and their application in drug testing.Frontiers in oncology · 2024Article
- Nitric oxide/paclitaxel micelles enhance anti-liver cancer effects and paclitaxel sensitivity by inducing ferroptosis, endoplasmic reticulum stress and pyroptosis.RSC advances · 2023Article
- Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles.Pharmaceutics · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since tumor stroma poses as a barrier to achieve efficacy of nanomedicines, it is essential to 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 of paclitaxel-loaded polymeric micelles (PTX-PMCs) and polymeric nanoparticles (PTX-PNPs) in a tumor stroma-mimicking 3D in vitro model. PTX-PMCs (77 nm) based on a amphiphilic block copolymer of mPEG-b-p(HPMAm-Bz) and PTX-PNPs (159 nm) based on poly(lactic-co-glycolic acid) were prepared, which had an encapsulation efficiency (EE%) of 81 ± 15% and 45 ± 8%, respectively. 3D homospheroids of mouse 4T1 breast cancer cells and heterospheroids of NIH3T3 fibroblasts and 4T1 (5:1 ratio) were prepared and characterized with high content two-photon microscopy and immunostaining. Data showed an induction of epithelial-mesenchymal transition (α-SMA) in both homo- and heterospheroids, while ECM (collagen) deposition only in heterospheroids. Two-photon imaging revealed that both fluorescently labeled PMCs and PNPs penetrated into the core of homospheroids and only PMCs penetrated into heterospheroids. Furthermore, PTX-PMCs, PTX-PNPs, and free PTX induced cytotoxicity in tumor cells and fibroblasts grown as monolayer, but these effects were substantially reduced in 3D models, in particular in heterospheroids. Gene expression analysis showed that heterospheroids had a significant increase of drug resistance markers (Bcl2, Abgc2) compared to 2D or 3D monocultures. Altogether, this study shows that the efficacy of nanotherapeutics is challenged by stroma-induced poor penetration and development of resistant phenotype. Therefore, this tumor stroma-mimicking 3D model can provide an excellent platform to study penetration and effects of nanotherapeutics before in vivo studies.
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