The Functional Gold Nanoclusters That Can Be Cleared By The Kidneys Are Used In The Research Of Intelligent Diagnosis And Treatment Of Tumors

Among many anti-cancer nanoagents,small sized nanoagents like nanoclusters?NCs?and nanodots,their tumor theranostic performance is always limited by size related fast renal clearance and dynamical escape from tumor tissue.But renal clearance is essential to maintain the biosecurity of nanoagents.Hence,it is challenging to enhance the theranostic performance by balancing renal clearance with tumor retention.In this work,our goal is to acquire efficient tumor accumulation by delaying the renal clearance and functional aggregation in tumor tissue.1.In the second chapiter,we chose biomass natural polysaccharide sodium alginate?SA?for stabilizing gold?Au?NCs.SA-Au NCs were synthesized by thermal reduction in aquous suspension,where SA acted as reducing agents and ligands.The average size of SA-Au NCs is 4.6 nm in TEM,but the dydrodynamic size was high to?20 nm.Contributed from SA ligands,SA-Au NCs possessed sensitive aggregation behavior in slightly acidic environment.The light extinction coefficient at 660 nm was increased from 0.09×10⁷ M^-1cm^-1 to 1.5×10⁷ M^-1cm^-1 after aggregation,indicating significant improved phtothermal converting performance.Due to biocompatibility of Au and SA,the SA-Au NCs are free of cytotoxicity and under the irradiation of a 660 nm laser,SA-Au NCs aggregates could efficiently abate cancerous cells in vitro.2.In the third chapiter,the theranostic performance of SA-Au NCs was tested in tumor models in vivo.Contributed from the ligands of SA,the half-life(t_1/2)of SA-Au NCs is prolonged to?9.3 h.The exsistence of SA did not hinder but delayed the renal clearance of NCs.As determined from the urine of mice,?54%of injected dose was urinated in the 1^stt day post injection.Comparing with literatures,agents at such size would urinate more than70%in the 1^st hour post injection.Also contributed form pH-sensitive SA,the SA-Au NCs could experience stimulated aggregation in tumor microenvironment?TME?,enhancing the tumor accumulation rate up to 10.4%ID/g.The TME responsive aggregation is functional.Before aggregation,the photothermal effect of SA-Au NCs is inactive in normal physical environment.After entering tumor area,animal experiments proved that SA-Au NCs aggregates were efficient photothermal therapy?PTT?agents for both local treatment of single tumors and systemic treatment of double-tumor models without causing noticeable side effects.Indicating the biosafety and feasibility of SA-Au NCs apply to system PTT.Combining with CT contrast imaging of Au,SA-Au NCs were efficient agents for tumor theranostics.