HSA-Binding Prodrugs-Based Nanoparticles Endowed with Chemo and Photo-Toxicity against Breast Cancer

Valentina Rapozzi, Francesca Moret, Luca Menilli, Andrea Guerrini, Daniele Tedesco, Marina Naldi, Manuela Bartolini, Mariachiara Gani, Sonia Zorzet, Marta Columbaro, Celeste Milani, Cecilia Martini, Claudia Ferroni, Greta Varchi

Research output: Contribution to journalArticlepeer-review

Abstract

Exploiting the tumor environment features (EPR effect, elevated glutathione, reactive oxygen species levels) might allow attaining a selective and responsive carrier capable of improving the therapeutic outcome. To this purpose, the in situ covalent binding of drugs and nanoparticles to circulating human serum albumin (HSA) might represent a pioneering approach to achieve an effective strategy. This study describes the synthesis, in vitro and in vivo evaluation of bioresponsive HSA-binding nanoparticles (MAL-PTX2 S@Pba), co-delivering two different paclitaxel (PTX) prodrugs and the photosensitizer pheophorbide a (Pba), for the combined photo-and chemo-treatment of breast cancer. Stable and reproducible MAL-PTX2 S@Pba nanoparticles with an average diameter of 82 nm and a PTX/Pba molar ratio of 2.5 were obtained by nanoprecipitation. The in vitro 2D combination experiments revealed that MAL-PTX2 S@Pba treatment induces a strong inhibition of cell viability of MDA-MB-231, MCF7 and 4T1 cell lines, whereas 3D experiments displayed different trends: while MAL-PTX2 S@Pba effectiveness was confirmed against MDA-MB-231 spheroids, the 4T1 model exhibited marked resistance. Lastly, despite using a low PTX-PDT regimen (e.g., 8.16 mg/Kg PTX and 2.34 mg/Kg Pba), our formulation showed to foster primary tumor reduction and curb lung metastases growth in 4T1 tumor-bearing mice, thus setting the basis for further preclinical validations.

Original languageEnglish (US)
Article number877
JournalCancers
Volume14
Issue number4
DOIs
StatePublished - Feb 1 2022

Keywords

  • Albuminbinding
  • Breast cancer
  • Combination therapy
  • Nanoparticles
  • Paclitaxel
  • Pheophorbide a
  • Prodrugs

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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