Development of pH-Sensitive Magnetoliposomes Containing Shape Anisotropic Nanoparticles for Potential Application in Combined Cancer Therapy
Ana Rita F. Pacheco,
Beatriz D. Cardoso,
Ana Pires,
André M. Pereira,
João P. Araújo,
Violeta M. Carvalho,
Raquel O. Rodrigues,
Paulo J. G. Coutinho,
Teresa Castelo-Grande,
Paulo A. Augusto,
Domingos Barbosa,
Rui A. Lima,
Senhorinha F. C. F. Teixeira,
Ana Rita O. Rodrigues,
Elisabete M. S. Castanheira
Affiliations
Ana Rita F. Pacheco
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Beatriz D. Cardoso
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Ana Pires
Associate Laboratory LaPMET, 4169-007 Porto, Portugal
André M. Pereira
Associate Laboratory LaPMET, 4169-007 Porto, Portugal
João P. Araújo
Associate Laboratory LaPMET, 4169-007 Porto, Portugal
Violeta M. Carvalho
MEtRICs, Mechanical Engineering Department, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal
Raquel O. Rodrigues
Center for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal
Paulo J. G. Coutinho
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Teresa Castelo-Grande
LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Paulo A. Augusto
LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Domingos Barbosa
LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Rui A. Lima
MEtRICs, Mechanical Engineering Department, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal
Senhorinha F. C. F. Teixeira
ALGORITMI Center, University of Minho, Campus de Azurém, 4800-058 Guimarães, Portugal
Ana Rita O. Rodrigues
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Elisabete M. S. Castanheira
Physics Centre of Minho and Porto Universities (CF-UM-UP), University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.
