ArticleInternational journal of nanomedicine2024
Preclinical Efficacy of Cabazitaxel Loaded Poly(2-alkyl cyanoacrylate) Nanoparticle Variants.
Article in International journal of nanomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.Acta pharmaceutica Sinica. B · 2026Review
- Evaluation of HER2 Targeted Poly(Ethylene Glycol)-Poly(L-histidine) Copolymer Micelles in Breast Cancer Models.Macromolecular bioscience · 2025Article
- Combinatorial Effects of Free and Nanoencapsulated Forms of Cabazitaxel and RAS-Selective Lethal 3 in Breast Cancer Cells.Pharmaceutics · 2025Article
- Applications of Matrix Metalloproteinase-9-Related Nanomedicines in Tumors and Vascular Diseases.Pharmaceutics · 2025Review
- PACA nanoparticles target and deliver sildenafil to rejuvenate aged mouse liver sinusoidal endothelial cells.Nanotheranostics · 2025Article
- Entry of nanoparticles into cells and tissues: status and challenges.Beilstein journal of nanotechnology · 2024Article
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Authors and funding
17 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect. Methods: Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry. Results: In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment. Conclusion: We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response.
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