Polysaccharide-Directed Fabrication Of Biomaterials For MR Imaging And Photothermal Therapy

Objective:Using polysaccharide biomolecular as template to fabricate biomaterials for imaging and therapy is a attracting strategy.It is urgent to develop new strategies for fabricating high-performance biomedical materials and promoting the potential clinical transformation.The clinical used MRI agents suffer from low relaxivity,fast blood circulation and lack of targeting ability.Besides,the complex synthesis and poor biocompatibility further restrict the bioapplication of MRI nanoagents.Herein,we propose polysaccharide-directed fabrication of a biosafe MRI nanoprobe with high relaxivity via a facile and efficient mimicking biomineralization method.Photothermal therapy?PTT?agents play a crucial role in tumor therapy,but most agents are limited by complicated synthesis processes and ambiguous biosafety.Herein,we propose to use polysaccharide biomolecular to fabricate iodine-starch hydrogel with good biocompatibility and photothermal conversion efficiency for tumor PTT.Materials and Methods:HA-Gd₂O₃ nanoprobe was constructed by using HA molecular as template to load Gd³⁺by one-pot reaction under alkaline condition at room temperature.The nanoprobe was characterized by HRTEM,DLS,FT-IR,XRD and XPS analysis.The biosafety of HA-Gd₂O₃ nanoprobe was assessed by MTT analysis,biodistribution assay,weight monitoring,blood biochemistry assessment and H&E staining,respectively.The relaxivity of HA-Gd₂O₃ nanoprobe and Gd-DTPA were determined,and their T₁-weighted imaging was compared in vivo.Iodine-starch complex was fabricated based on the classic and simple“iodine-starch test”,and further dispersed it into alginate-Ca²⁺hydrogel to fabricate iodine-starch hydrogel.The iodine-starch hydrogel was characterized by UV spectra,FT-IR,FE-SEM and injectable experiment.The stability of iodine-starch hydrogel was assessed under reductive environment.The heat conversion efficiency was measured by an 808nm laser irradiation.The biosafety of iodine-starch hydrogel was assessed by MTT analysis,weight monitoring and H&E staining,respectively.The tumor ablation ability using iodine-starch hydrogel was assessed in vitro and in vivo.Results:The HA-Gd₂O₃ nanoprobe exhibited good colloidal stability and high T₁ relaxivity(14.95 mM^-1s^-1 at 0.5 T).The toxicity evaluations proved low cytotoxicity and good biocompatibility in vivo of the nanoprobe.The T₁-weighted imaging of mice administrated with HA-Gd₂O₃ nanoprobe showed a superior contrast enhancement compared with Gd-DTPA.Besides,the HA-Gd₂O₃ nanoprobe can serve as a high-performance MRI agent for targeted adrenal gland imaging.The deep blue iodine-starch hydrogel was successfully obtained with good stability and desirable photothermal conversion efficiency?17.2%?.Besides the hydrogel displayed a good tumor ablation capability in vivo and in vitro under the laser irradiation.A series of toxicity assessments confirmed its good biocompatibility.Conclusion:In this section,we employed polysaccharide biomolecular to fabricate Gd₂O₃nanoprobe with good biocompatibility and high T₁ relaxivity,which was successfully used in targeted adrenal gland imaging in vivo.This work provides a novel strategy to design MRI contrast agent with high sensitivity,and broaden polysaccharide-directed synthesis methodology for biomedical applications.In this section,the classic iodine starch test and alginate are used to obtain iodine-starch hydrogel with good photothermal conversion ability.This is the first time to use iodine-starch for tumor PTT.This work enriches the application of polysaccharide-guided synthesis of biomaterials in tumor therapy.