Incorporation of paclitaxel into hollow-p4VP nanoparticles to improve breast cancer chemotherapy

Maria del Carmen Leiva Arrabal

Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.

Maria del Carmen Leiva Arrabal is a 4º year PhD student at the University of Granada, concretelly at the Institute of Biopathology and Regenerative Medicine (IBIMER). Her research is about the delivery of drugs used for the treatment of breast and lung cancer, especially paclitaxel. The aim of her work is to improve the current chemotherapy by incorporating these drugs into nanoparticles to decrease toxicity and enhance their antitumoral effect. She is responsible for the study of the biological activity of the drug-loaded nanoparticles over several tumor models.

Julia Jiménez-López

This presenter did not provide a biography.

Abstract

Introduction: Paclitaxel (PTX) is being currently used in the treatment of breast cancer, though it presents some drawbacks as low solubility, no tumor specificity and high toxicity. PTX loading into nanoparticles (NPs) may overcome those limitations, avoiding the use of toxic Cremophor EL in the formulation, and improving treatment efficiency. In this work, we have developed hollow poly(4-vinylpyridine) nanoparticles (p4VP) for PTX delivery, and their biocompatibility and antitumor activity against breast cancer has been in vitro studied.
Methods: Firstly, biocompatibility of p4VP was analyzed by a hemolysis assay with human blood. Sulphorrodamine B method was used to compare PTX and PTX-loaded p4VP (PTX@p4VP) cytotoxicity on human breast MCF7 cancer cells and MCF-10A normal cell line. Moreover, their activity against multicellular tumor spheroids (MTS) formed from MCF7 cells, was studied by tracking their volume every 2 days, and by immunostaining with TUNEL to compare cell death after different treatments.
Results: Hemolysis assay with human blood proved no toxicity of p4VP. In addition, cell death was improved by the use of PTX@p4VP in both cell lines, whereas the effect was more evident on tumor cells (2.9-fold reduction of PTX IC50 vs 1.7-fold). Furthermore, MTS treated with PTX@p4VP showed a significant volume reduction than those treated with PTX. However, both treatments achieved a reduction in MTS volume in comparison to controls and blank p4VP. Immunofluorescence corroborated those data by staining death cells on the surface of MTS treated with PTX and PTX@p4VP.
Discussion: According to those results, p4VP present good biocompatibility that make them suitable for in vivo drug delivery. They are also able to enhance PTX antitumor effect against breast cancer cells and breast MTS, which resemble tumor mass. In the light of our findings, PTX@p4VP represent a promising delivery system for the improvement of chemotherapy involved in the treatment of breast tumor.

Authors

Maria del Carmen Leiva Arrabal (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Julia Jiménez-López (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Rafael Contreras-Caceres (Department of Organic Chemistry, University of Málaga, Málaga, Spain.)
Laura Cabeza (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Gloria Perazzoli (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Raúl Ortiz (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Department of Health Sciences, University of Jaén, Jaén, Spain.)
Consolación Melguizo (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)
Juan Manuel López-romero (Department of Organic Chemistry, University of Málaga, Málaga, Spain.)
Jose Prados (Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.)

Topic Area

Nanomedecine for cancer diagnosis & therapy

Session

PS2 » Poster Session & Sponsors Exhibition (13:30 - Thursday, 29th September, Patio 25)

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