Development of Thermo- and pH-Sensitive Liposomal Magnetic Carriers for New Potential Antitumor Thienopyridine Derivatives.

Beatriz C Ribeiro,Elisabete M S Castanheira,Ana Pires,André M Pereira,Paulo J G Coutinho,João P Araújo,Cristina A R Alvarez,Bernardo G Almeida,Juliana M Rodrigues,Bárbara C Alves,Maria João R P Queiroz,Ana Rita O Rodrigues

doi:10.3390/ma15051737

Beatriz C Ribeiro, Elisabete M S Castanheira + Show 10 more

Open Access

https://doi.org/10.3390/ma15051737

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Journal: Materials	Publication Date: Feb 25, 2022
Citations: 11	License type: CC BY 4.0

Affiliation: University of Minho, University of Porto

Abstract

The development of stimuli-sensitive drug delivery systems is a very attractive area of current research in cancer therapy. The deep knowledge on the microenvironment of tumors has supported the progress of nanosystems’ ability for controlled and local fusion as well as drug release. Temperature and pH are two of the most promising triggers in the development of sensitive formulations to improve the efficacy of anticancer agents. Herein, magnetic liposomes with fusogenic sensitivity to pH and temperature were developed aiming at dual cancer therapy (by chemotherapy and magnetic hyperthermia). Magnetic nanoparticles of mixed calcium/manganese ferrite were synthesized by co-precipitation with citrate and by sol–gel method, and characterized by X-ray diffraction (XRD), scanning electron microscopy in transmission mode (STEM), and superconducting quantum interference device (SQUID). The citrate-stabilized nanoparticles showed a small-sized population (around 8 nm, determined by XRD) and suitable magnetic properties, with a low coercivity and high saturation magnetization (~54 emu/g). The nanoparticles were incorporated into liposomes of dipalmitoylphosphatidylcholine/cholesteryl hemisuccinate (DPPC:CHEMS) and of the same components with a PEGylated lipid (DPPC:CHEMS:DSPE-PEG), resulting in magnetoliposomes with sizes around 100 nm. Dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements were performed to investigate the pH-sensitivity of the magnetoliposomes’ fusogenic ability. Two new antitumor thienopyridine derivatives were efficiently encapsulated in the magnetic liposomes and the drug delivery capability of the loaded nanosystems was evaluated, under different pH and temperature conditions.

Highlights

Licensee MDPI, Basel, Switzerland.Tumors are characterized by a specific microenvironment due to the uncontrolled cell proliferation, acidic pH, overexpression of proteins and enzymes and high levels of oxidation/deoxidation, as a result of the peculiar nutritional environment and of the metabolic pattern change of tissues
The X-ray diffraction (XRD) pattern of the synthesized nanoparticles was obtained and the data analysis was processed by Rietveld optimization using the Profex/BGMN software [27,28]
These results reveal slightly smaller diameters than the size distribution obtained from the Dynamic light scattering (DLS) measurements, as the latter comprise the liquid layer around the nanosystem, while Scanning Electron Microscopy (SEM) measures the size of the dry nanoparticles

Summary

Introduction

Tumors are characterized by a specific microenvironment due to the uncontrolled cell proliferation, acidic pH, overexpression of proteins and enzymes and high levels of oxidation/deoxidation, as a result of the peculiar nutritional environment and of the metabolic pattern change of tissues. Based on these characteristics, endogenous and exogenous stimuli have been strategically studied as triggers in the development of controlled drug-delivery nanosystems [1,2]. Magnetic fields can precisely control heat generation to induce drug release from thermo-responsive nanosystems, while overheating cancer cells [4,5]

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