Magnetite Nanoparticles Coated with Biodegradable Zwitterionic Polymers as Multifunctional Nanocomposites for Drug Delivery and Cancer Treatment

Abstract

Tailor-made materials for biomedical applications can be constructed with different building blocks to confer multiple functions on one platform. Here, we demonstrate the facile synthesis of magnetite-biodegradable polymer nanocomposites combining superparamagnetism with the possibility of loading and controlling the release of a lipophilic drug. The magnetite nanoparticles were synthesized by reduction–precipitation and used as nuclei to grow a biodegradable zwitterionic shell. The copolymer used for this scope comprises a hydrophobic block made of a biodegradable ε-caprolactone-based macromonomer (CL n ) with three different degrees of polymerization (DP n , n = 3, 5, and 7) obtained by ring-opening polymerization (ROP). Dopamine molecules were attached to the end of this CL n oligomer (CL n Dopa), conferring a specific affinity for the magnetite surface. A hydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) block (PMPC) was included by reversible addition–fragmentation chain transfer (RAFT) polymerization to add colloidal stability and water dispersibility to the copolymer. This PMPC was chain-extended with CL n Dopa via RAFT polymerization targeting four different DP m (m = 10, 20, 30, and 40), resulting in a library of 12 copolymers. A facile nanoprecipitation process produced copolymer nanoparticles and copolymer-coated magnetite nanostructures. Physicochemical characterization confirmed the inorganic–organic composite nature. The copolymer-coated magnetic materials showed water stability, superparamagnetic behavior, and appropriate hyperthermic ability under an alternate magnetic field. Biological assays using HeLa cells showed high biocompatibility and efficient nanoparticle uptake. In addition, a sustained release of dexamethasone, used as a model drug encapsulated in the polymer shell, and local heating as a dual functional material could be accessed.

Iron Oxide Nanoparticles Coated with Biodegradable Block-Copolymer PDMAEMA-b-PMPC and Functionalized with Aptamer for HER2 Breast Cancer Cell Identification

“…First, we synthesized and characterized the polymers separately and then the blockcopolymer. As a result, we observed a DPexperimental above of DPtheoretical for PMPC, also found in another study about PMPC synthesis by RAFT (Perecin et al, 2022). Furthermore, our results indicated a low monomer conversion of DMAEMA in PDMAEMA and the block-copolymer PDMAEMA-b-PMPC, with the same pattern previous studies (L. Wang et al, 2019).…”

“…First, we synthesized an IONP using the classical co-precipitation method and confirmed the chemical composition using XRD, FT-IR, UV-VIS, TGA, and SAED techniques. XRD confirms the formation of iron oxide nanoparticles with a classical pattern of other studies (Cornell & Schwertmann, 2003b;Perecin et al, 2022) corresponding to an inverse spinel structure. However, XRD cannot detect the differences between maghemite and magnetite because these two phases are isostructural.…”

“…The FT-IR spectra demonstrated the magnetite formation (580 cm -1 characteristic band) and some nanoparticle surface adsorbed molecules. These 1000-1200 cm -1 bands represent the sulfur group residue of the synthesis, which is observed in other studies (Perecin et al, 2021(Perecin et al, , 2022 and can be helpful to colloidal stabilization. Also, the bands between 600 and 650 cm -1 are associated with the Fe-O stretching related to the maghemite phase, indicating some oxidation of our IONPs.…”

“…Therefore, we used a biodegradable blockcopolymer PDMAEMA-b-PMPC to encapsulate the IONPs. PMPC was chosen to provide colloidal stability and better biocompatibility (Goda et al, 2015b;Perecin et al, 2022), while PDMAEMA binds to acid nuclei by electronic binding (C. Zhu et al, 2010).…”

Carbon-Coated Iron Oxide Nanoparticles Promote Reductive Stress-Mediated Cytotoxic Autophagy in Drug-Induced Senescent Breast Cancer Cells

“…Surface-modified magnetic nanoparticles (NPs), such as magnetite (Fe 3 O 4 ) NPs, in the form of multifunctional nanoplatforms and/or biocompatible core–shell nanostructures, are powerful theranostic tools with numerous biomedical applications, for example, bioimaging, biosensing, drug and gene delivery, and hyperthermia. − However, uncontrolled release of ferric iron from Fe 3 O 4 NPs may promote the generation of reactive oxygen species (ROS) and related toxicity in biological systems that can be considered as a double-edged sword with detrimental effects in normal cells and tissues and, if programmed, therapeutic effects against cancer cells and solid tumors. − It is widely accepted that oxidative stress, a result of increased production of ROS and/or diminution in the antioxidant defense system ( e.g. , decreased levels of antioxidants, decreased functionality of antioxidant transcription factors), may promote oxidative damage to biomolecules that may be associated with the initiation and progression of human pathologies, such as age-related diseases, namely, neurogenerative and cardiovascular disorders and cancer .…”