Thermally Responsive Peptide Coated Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery

Abstract

Target specific delivery of anticancer drugs to the effected site without showing systematic toxicity to normal tissues is important. Multifunctional biodegradable delivery systems reduce systematic toxicity in an efficient manner. These drug carriers should provide controlled release, be directed towards desired site, track payloads via contrast imaging, heat the effected sites and trigger drug release. In this context, superparamagnetic iron oxide nanoparticles based drug delivery systems are highly desirable. Superparamagnetic iron oxide nanoparticles upon exposure of alternate magnetic field could be directed and provide heat to localised areas. Moreover, superparamagnetic iron oxide nanoparticles also have image contrast ability for magnetic resonance imaging.
This study aimed to develop biocompatible superparamagnetic iron oxide nanoparticles. These nanoparticles were coated by bioinspired materials such as peptides (diphenylalanine) to achieve monodispersed dual efficient such as drug carriers and hyperthermia. Thermally responsive core-shell materials with tubular and spherical morphologies without compromising the inner cores properties such as superparamagnetism is highly desirable.
Two shapes of iron oxide (spherical and tubular) were prepared using co-precipitation of iron (II) and (III) ion and oxidative hydrolysis of ferrous sulphate in alkaline solutions, respectively. Spherical peptide shells were synthesised using tert-Butyloxycarbonyl modified diphenylalanine peptide in ethanol-water (1:1) mixture. Tubular peptide shells were prepared using similar diphenylalanine non-modified peptide. The iron oxide nanoparticles (spherical and tubular) were encapsulated via template-mediated synthesis using ultra-sonication and vortex-mixing methods.
These materials were characterised using variety of techniques such as, zetasizer, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDAX), Fourier Transform Infrared Spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) analysis, Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Vibrating Sample Magnetometer (VSM) and magnetic field induced hyperthermia. The diameter of spherical superparamagnetic iron oxide nanoparticles were measured to be ranges from 10 to 35 nm and rod-shaped core materials showed nearly 10 nm width and several hundred nanometres in length. Spherical peptide were approximately 1 µm in diameter. Tubular-shaped peptide were between 100-300 nm in width and several micrometres in length. These peptides were used as shells for the preparation of core-shell composites. Both spherical and rod-shaped core-shell composites were similar in dimensions to the pure peptide particles. Observational analysis confirmed the presence core-shell composition. Spherical iron oxide core materials were crystalline magnetite (Fe3O4) structures confirmed by powder XRD. These magnetite nanocrystals were further modified with a biocompatible silica shell. Brunauer–Emmett–Teller (BET) analysis revealed a mesoporous shell structure. Spherical peptide shells were found to be amorphous and tubular peptide shells were crystalline in nature. VSM of core-shell composite materials depicted superparamagnetic nature, hence these materials have ability to heat over the exposure of applied external magnetic field for hyperthermia ablation.
Anticancer drug (doxorubicin, DOX) loading and release profile of bare spherical and rod-shaped iron oxide nanoparticle and peptide, silica and peptide-capped silica coated spheres were studied for potential therapeutic application. The doxorubicin loading efficiency was observed to be ranging from 12 % to 90 % depending on the type materials. The in vitro drug release profiles were measured at 37 °C without the exposure of magnetic field in incubation and with applied magnetic field. Time-dependent studies showed sustained release of DOX in silica coated and peptide- capped silica coated spherical superparamagnetic iron oxide nanoparticles were ranging from 0 to 30 % over 72 hours of incubation. Concentration dependent studies revealed that the ratio of 1:100 (doxorubicin:superparamagnetic iron oxide nanoparticles) had the maximum loading efficiency with minimum release capability. Exposure to Alternate Current (AC) magnetic field (200 G; 406 kHz) the spherical materials generated hyperthermia in a time dependent manner reaching 50 °C in 3 minutes. Tubular peptide coated iron oxide materials did not induce heat even after 25 minutes of exposure indicating weak superparamagnetism. Magnetic field triggered drug release was seen only in spherical core-shell nanocomposites with 6X higher compared at 37 °C without exposure.