Sdudy On The Preparation Of Gadolimium Contained,Stimuli-responsive Polymer Particles And Their Application In Theranostics

Magnetic resonance imaging (MRI) contrast agents on the basis of gadolinium modified with smart polymer have great applicantions in clinical. However, as the development of theranostics, agents only for diagnosis are far from enough. Therefore, theranostic agents come to the forefront and become popular. Nevertheness, using a facile and environmently friendly way to fabricate such theranostic agent is a big chanllenge. Hence, designing a facile and environment friendly way to prepare multifunctional probe with superior property which is based on MRI diagnosis is of great dignificance.In this article, the theranostic agents are obtained by emulsifier-free emulsion polymerization. The agent are consist of the copolymer of N-isopropylacrylamide (NIPAM), methacrylic acid (MAA), and styrene (St) which have loaded gadolinium conpounds, anticancer drug, or europium. The chemical structure, morphology, particle size, stability, drug loading ability, biocompatibility, anticancer ability, and in vivo MR optical imaging property of the polymeric particals are investigated.Firstly, a gadolinium monomer [Gd(AA)3·phen·H2O] is synthesized. A paramagnetic, pH and temperature-sensitive polymeric particle (PPP) is synthesized in the presence of NIPAM, MAA, and St using KPS as a initiator. These dually sensitive polymeric particles show negligible cytotoxicity against HeLa and glioma (C6) cells. The obtained polymeric particles can effectively load anticancer drug doxorubicin (DOX). In vitro drug release measurements exhibit retarded release profile when subjected to varying pH or temperature. Moreover, DOX-loaded PPP exhibits obvious antitumor properties for C6 cells. The percentage of cumulative DOX release can reach to 96%while both pH and temperature are changed. The TV-weighted relaxivity values at 3 Tare 12.41 mM-1 s-1 (pH= 6.3) and 10.75 mM-1 s-1 (pH= 7.4). In vivo MRI reveals that the PPPs are resultful in brain tumor (glioma).On the basis of above work, we choose gadolinium oxide nanoparticles as MRI contrst agent and europium as optical probe. Gadolinium oxide and europium-encapsulated temperature/pH-responsive polymeric particles (PLTPPs) synthesized by emulsifier-free emulsion polymerization show good biocompatibility with C6 and H22 cells and anticancer drug (doxorubicin, DOX) loading capability. In vitro drug release assessment discloses release abatement under lower pH or in hotter conditions, and the DOX-loaded PLTPPs have obvious antitumor properties for C6 and H22 cells. Cellular uptake tests confirm that the materials can be taken up by C6 cells to facilitate optical imaging. The T1-weighted relaxivity value at 3 T is 6.13 mM-1 s-1 which is 39% higher than that of the clinical Magnevist(?). In vivo MR and optical imaging reveal that the PLTPPs are effectively dual probes.