Abstract
In the present work, we prepare thermo- and pH-sensitive polymer-based nanoparticles incorporating with magnetic iron oxide as the remote-controlled, stimuli-response nanocarriers. Well-defined, dual functional tri-block copolymer poly[(acrylic acid)-block-(N-isopropylacrylamide)-block-(acrylic acid)], was synthesized via reversible addition-fragmentation chain-transfer (RAFT) polymerization with S,S′-bis(α,α′-dimethyl-α″-acetic acid)trithiocarbonate (CMP) as a chain transfer agent (CTA). With the aid of using 3-aminopropyltriethoxysilane, the surface-modified iron oxides, Fe3O4-NH2, was then attached on the surface of self-assembled tri-block copolymer micelles via 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinamide (EDC/NHS) crosslinking method in order to furnish not only the magnetic resources for remote control but also the structure maintenance for spherical morphology of our nanocarriers. The nanocarrier was characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible (UV/Vis) spectral analysis. Rhodamine 6G (R6G), as the modeling drugs, was encapsulated into the magnetic nanocarriers by a simple swelling method for fluorescence-labeling and controlled release monitoring. Biocompatibility of the nanocarriers was studied via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed that neither the pristine nanocarrier nor the R6G-loaded nanocarriers were cytotoxic to the normal fibroblast cells (L-929 cells). The in vitro stimuli-triggered release measurement showed that the intelligent nanocarriers were highly sensitive to the change of pH value and temperature rising by the high-frequency magnetic field (HFMF) treatment, which provided the significant potential to apply this technology to biomedical therapy by stimuli-responsive controlled release.
Highlights
Over the past decades, polymeric nanoparticles have received great interests in drug delivery systems owing to their drug loading capacity and biocompatibility for targeting therapy [1]
The molecular weight of tri-block copolymer was calculated by Equation 4 as below: Mn 1⁄4 MnPAA;Gel permeation chromatography (GPC) þ MnPNIPAAm;Nuclear magnetic resonance spectroscopy (NMR)
Where Mn refers to the number average molecular weight of copolymer, and MnPAA,GPC stands for the number average molecular weight of poly(acrylic acid) (PAA) estimated via GPC
Summary
Polymeric nanoparticles have received great interests in drug delivery systems owing to their drug loading capacity and biocompatibility for targeting therapy [1]. Polymeric nanoparticles were able to load therapeutic agents, usually hydrophobic drugs, in the hydrophobic core region, while the hydrophilic shell region provided good dispersion in water and reduced the toxicity [2]. Polymeric nanoparticles have shown prolonged-circulation characteristics and great-. Since the LCST was close to the human body temperature, hydrophilic-segments, like acrylic acid (AA), were introduced into PNIPAAm for LCST tuning by copolymerization [9], surface modification, or physical blending in order to prepare hollow structured nanoparticles via thermo-triggered self-assembling. In spite of the benefits for drug delivery, the practical controlled release was still hindered with poor in vivo colloidal stability [11], which often caused low therapeutic efficiency and side effects
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