Preclinical Efficacy of Cabazitaxel Loaded Poly(2-alkyl cyanoacrylate) Nanoparticle Variants

Int J Nanomedicine. 2024 Mar 26:19:3009-3029. doi: 10.2147/IJN.S450283. eCollection 2024.


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.

Keywords: breast cancer; cabazitaxel; patient-derived xenograft; poly(alkyl cyanoacrylate); tumor microenvironment.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Cyanoacrylates
  • Drug Carriers
  • Female
  • Folic Acid
  • Humans
  • Nanoparticles*
  • Taxoids*
  • Tissue Distribution
  • Tumor Microenvironment


  • cabazitaxel
  • polyethylbutylcyanoacrylate
  • Drug Carriers
  • Cyanoacrylates
  • Folic Acid
  • Taxoids

Grants and funding

The work was supported by a grant from The Norwegian Cancer Society (Project no. 208239) to KS/TGI and from the Regional Health Authorities in South-East Norway (Project no. 2022069) to GMM/LP. GMM, SMM and JHH also acknowledge support from the Maria Sklodowska-Curie Actions (MSCA-ITN-2020 grant agreement ID: 956544 (DIRNANO: Directing the Immune Response through Designed Nanomaterials)). JHH additionally acknowledges support by the County of Salzburg, Cancer Cluster Salzburg (grant number 20102-P1601064-FPR01-2017) and by the Priority program ACBN, University of Salzburg. AK was supported by a grant from The Research Council of Norway (Project no. 346892).