Synthesis of Magnetic Field-Responsive Nanocomposites and the Magnetic Hyperthermia Biological Effects

Author:Gao Fei

Supervisor:fan hai ming


Degree Year:2019





Due to their unique magnetic properties and good biocompatibility,comparable size to functional biomolecules,metabolic behavior,the magnetic field-responsive functional magnetic nanoparticles(MNPs)have been considered as one of the most promising materials for biomedical applications.Recently,many functional nanocomposites with MNPs-core have been widely used,such as tumor molecular imaging,magnetic hyperthermia(MHT).It also can produce the thermal and mechanical forces at nanoscale to induce many kinds of biological effects.Despite the stated advantages of MNPs,there are some challenges to their use from bench to bed,for example,owing to the low specific absorption rate of embedded MNPs in hydrogel formulations,the balance between maintaining the useful rheological properties of the hydrogel and the nanoparticle loading concentration presents a challenging obstacle,the contradiction between the efficiency of MHT media and its biological safety,the controversy of magnetic field-induced nanoscale thermal phenomena,and so on.How to achieve high efficiency treatment with low toxicity is still faces serious bottleneck problem.Based on the above problems,we have carried out the following studies:1.We report a novel magnetic cocktail hydrogel functionalized by ferrimagnetic vortex-domain iron oxide(FVIOs)with optimally adaptive functions for prevention breast cancer recurrence.The FVIOs with higher specific absorption rate(SAR)can perfectly incorporate into the dynamic hydrogel networks with an extremely low concentration(0.6 mg/mL),17times lower than that of conventional SPIOs with sufficient heating capacity.Such magnetic hydrogels exhibited high inductive heating and remarkable rheological properties simultaneously.The gelation time,Young moduls,self-conformal and self-healing properties of the hydrogel were not influenced by the FVIOs with low concentration.The biodegradation and drug release behavior regulated the anticancer drug in a sustained manner and selectively targeted potential microscopic lesions directly for a longer time.The cell treated with DOX load magnetic cocktail hydrogel confirm the magnetic hyperthermia effect on the DOX diffusion into the nucleus.In vivo postoperative treatment has further demonstrated the high efficacy of FVIO-based magnetic hydrogel,as evidenced by the significant suppression of the local tumor recurrences compared to chemotherapy or hyperthermia alone.This unique magnetic hydrogel formulation with optimally adaptive functions shows strong potential in preventing relapses of various cancers.2.We applied the nonmagnetic materials-hypertonic saline(HTS)induced magnetic heating effect in the magnetic mediated hyperthermia(MMT),and incorporated it into the hydrogel formulations to prevent the breast cancer postsurgical recurrence.In view of the existing problems of potential risk of long-term side effects and relatively poor energy transfer efficiency of magnatic iron nanoparticles,we re-consider the definition of MMH mediators,and a clinical applied solution exhibiting several physiological effect under alterative magnetic field(AMF),was systematically investigated.The HTS can induce enough high and rapid temperature increase upon exposure under AMF.The inductive heating profiles of many different kinds of salt solutions were also evaluated and the heating machnism may due to the dipolar polarization under the electromagnetic radiation.PEG based HTS hydrogel was fabricated for inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time.Furthermore,an anticancer drug(doxorubicin)was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli responsive drug sustainable release,as well as synergistic thermo-chemotherapy for breast cancer postsurgical recurrence prevention.This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli responsive chemotherapy for breast cancer postsurgical recurrence prevention.3.The nanozyme,amorphous iron nanoparticles(AIronNPs)were employed to investigate the AMF induced magneto-dynamic enhanced antibacterial effect without increasing the macroscopic temperature.The continuous activity may give the bacteria an opportunity in developing resistance against these nanozymes,thus,we introduce the AMF as an external“trigger”with the capacity to tune the antibacterial activity.Both Gram-positive and Gram-negative bacteria were chosen to confirm the effect of AMF irradiation on the antibacterial efficiency of AIronNPs.The magnetic heating capacity,inherent endogenous activity of generating hydroxyl radicals(·OH)and the catalytic kinetics of nanozyme showed that the elevated peroxidase-like catalytic activities might be attributed to the better electron transportation capacity and the local nanoscale heating effects with AMF exposure with a very low dose of H2O2.The AMF indueced magneto-dynamic effect could control over ROS production and enhanced the antibacterial activity.It also facilitated the formation of granulation tissue and accelerated the wound healing in wound infection-healing model of mice.These systematic findings will pave an avenue for the development of AMF mediated stimuli-responsive nanozymes for treatment of infectious diseases and tackling the resistance against antibiotics in future.