Magnetic particle ornamented dual stimuli responsive nanogel for controlled anticancer drug delivery

Abstract

A series of spherical magneto-responsive nanogels were fabricated by formulating different sets of star block copolymers based on pentaerythritol–poly(ε-caprolactone)-b-poly(acrylic acid) (PE–PCL-b-PAA) combined with amine-functionalized magnetic nanoparticles for targeted cancer therapy. Superparamagnetic nanoparticles, Fe₃O₄ (5 ± 0.5 nm), were modified with (3-aminopropyl)trimethoxysilane to introduce the amine functionality into the system which also imparts colloidal stability. In the star block copolymer, the hydrophilic PAA chain length has an architecture such that it can accommodate a large number of amine-functionalized magnetic nanoparticles. The hydrodynamic size of the nanogel has been observed in the range of 65 ± 2 nm to 616 ± 7 nm. The as-prepared nanogel has been employed to deliver an anticancer drug, doxorubicin (DOX). A maximum of 20% of DOX encapsulation has been observed. In the presence of physiological pH of cancer cells (pH 5), the nanogel is able to deliver 73% of drug in 24 h which is further enhanced in the presence of an external static magnetic field (76% release). Under the influence of a high-frequency alternating magnetic field the in vitro drug release rate is 56% h⁻¹. The low viscosity (0.21 Pa s) at high shear rate (1000 s⁻¹) makes the nanogel suitable for painless injection. The pristine nanogel shows about 80% cell viability against the C6 glioma cell line. The magnetic field-induced targeting effect (cell uptake) of the fabricated nanogel has been visualized by fluorescence confocal microscopy. The therapeutic effect of the DOX-loaded nanogel has been examined against the C6 glioma cell line and it is found that the DOX-loaded magnetic nanogel having a composition of PE–PCL₂₀-b-PAA₁₈₀ with 10% amine-modified Fe₃O₄ shows selectively high toxic (IC₅₀ = 3.85 μg mL⁻¹) effect towards the C6 glioma cell line. This kind of new class of magnetic nanogel can open a new direction for MRI-guided drug delivery systems.