Abstract

The delivery of multiple anti-cancer agents holds great promise for better treatments. The present work focuses on developing multifunctional materials for simultaneous and local combinatory treatment: Chemotherapy and hyperthermia. We first produced hybrid microgels (MG), synthesized by surfactant-free emulsion polymerization, consisting of Poly (N-isopropyl acrylamide) (PNIPAAm), chitosan (40 wt.%), and iron oxide nanoparticles (NPs) (5 wt.%) as the inorganic component. PNIPAAm MGs with a hydrodynamic diameter of about 1 μm (in their swollen state) were successfully synthesized. With the incorporation of chitosan and NPs in PNIPAAm MG, a decrease in MG diameter and swelling capacity was observed, without affecting their thermosensitivity. We then sought to produce biocompatible and mechanically robust membranes containing these dual-responsive MG. To achieve this, MG were incorporated in poly (vinyl pyrrolidone) (PVP) fibers through colloidal electrospinning. The presence of NPs in MG decreases the membrane swelling ratio from 10 to values between 6 and 7, and increases the material stiffness, raising its Young modulus from 20 to 35 MPa. Furthermore, magnetic hyperthermia assay shows that PVP-MG-NP composites perform better than any other formulation, with a temperature variation of about 1 °C. The present work demonstrates the potential of using multifunctional colloidal membranes for magnetic hyperthermia and may in the future be used as an alternative treatment for cancer.

Highlights

  • Cancer is a severe disease with increasing incidence and related deaths, being considered the second cause of death worldwide

  • It was demonstrated that monodisperse bare Fe3 O4 NPs with an average diameter of 9.4 ± 1.9 nm

  • A dual-stimuli responsive system was developed composed of magnetic nanoparticles incorporated into thermoresponsive microgels, which in turn were incorporated into PVP electrospun membranes

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Summary

Introduction

Cancer is a severe disease with increasing incidence and related deaths, being considered the second cause of death worldwide. Current cancer treatments are focused on surgery (about 50%), chemotherapy, and radiotherapy, which present a low degree of personalization to the cancer type, leading to their therapeutic inefficiency and severe side effects [1,3]. There are often problems with resistance and levels of toxicity (side effects) [6]. This can be attributed, at least in part, to the poor local delivery of therapeutic agents, which makes the development of multifunctional systems that deliver medicines locally to the tumor a promising area of research in cancer. The ability to combine different systems and their various properties widens the field of the device’s potential applications, allowing a more personalized treatment

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