Study On The Synthesis,characterization And Activity Of Bovine Serum Protein-Manganese Nanocomposites

Phototherapy has become a common therapy due to the advantages of low toxicity,small trauma,good selectivity and repeatable treatment.It mainly consist of photodynamic therapy（PDT）and photothermal therapy（PTT）.The PDT is a noninvasive,low toxicity side of treatment.Which is constituted by the light source,oxygen and photosensitizer.PTT is a treatment for killing cancer cells by using a high photothermal conversion and efficiency of medicine.However,it cannot completely eradicate cancer cells due to the limitation of light penetration depth and the lack of targeting.The conbonation of PTT and PDT colud effectively promote the transmission of photothermal reagents and photosensitizers,and enhance the anti-cancer effecciency.Therefore,the high activities and targeting of phototherapy reagents will be a key point for tumor diagnosis and treatment than single therapy.This research have summarized the application of the compounds in the PDT and PTT treatment for tumor.Three BSAMn nanocomposites were designed and synthesized.The nanoparticles were analyzedby IR,UV,TEM and AAS.The property of catalytic water oxidation,the effect of photothermal conversion and in vivo/vitro activity have been studied.The main innovations are shown as follows:（1）Pyrrolidinone manganese complexes（PdpaMn）is a supermolecular compounds（Mn-DBA）on the basis of fluoroboron-based fluorescent compounds（DBA）via hydrogen bonding.Then it was self-assembly with BSA to form a nanoparticle with core-shell structure.The protein is the shell and Mn-DBA is the nuclear.Next,the nanoparticle was modificated with polyethylene glycol folic acid（PEG-FA）and obtained a multi-functional nanoparticle（Mn-DBA@BSA-PF）with low toxicity,targeting,magnetic resonance imaging and optical treatment capacity.It was found that this nanoparticle shows highly stability under neutral conditions,and could acid-induced release the anti-cancer Mn-DBA.The Mn-DBA was highly accumulated in tumor,and inhibited expression of lactate dehydrogenase（LDH-A）.Manganese nanoparticles could simultaneously act as T1 signal contrast agents.The nanoparticles shows excellent heat treatment effect and catalytic water oxidation activity under red LED light irradiation due to the energy transfer between hydrogen-driven dye and Mn complex.It is the first time to report the protein nanoparticles which consist of manganese complexes and fluorescent compounds for the diagnosis and treatment of tumor.（2）A novel nucleic acid aptamer modified targeted lactate oxidant Mn-D@BPFeA was systhesized,and it can effectively inhibits the expression of HIF-1α.These nanoparticles can act as nanoreactors and exhibit the performance of water oxidationin vivo or vitro with light driven.The carboxyl was firstly coordinated with Fe³⁺ and then recognited the adapter GAG.The functionalized nanoparticles that modified with nucleic acid aptamers exhibit high tumor accumulation,low biotoxicity and light enhanced anticancer properties.The DOX-manganese complex exhibites charge transfer effect between the ligand and the metal property of water oxidation and selectively oxidation of the lactic acid to reduce the lactic acid level of the tumor tissue under the light illumination.In addition,the combination of drug DOX and nanoparticles cause to the phototherapy effect,which reflects the combination of dualoptical therapy and chemotherapy.Targeted nanoparticles successfully inhibit expression of HIF-1α and glucose transporter（Glut-1）in HepG-2 cells,which provides a new idea for the synthesis of novel multifunctional nanoreactors.（3）Mn-CuS@BSA-FA is a new lactic acid oxidant that coupled with manganese complex and nano-CuS.The characterized results show that the nanoparticles have excellent photothermal effect and inhibition for glycolysis process with 808 nm laser irradiation.Additionally,the nanoparticles exhibit an excellent photothermal conversion efficiency in tumor cells due to the interaction of Manganese complex and carboxyl groups on the surface of CuS The hydroxyl radicals were produced in the process of water oxidation with the irradiation of near infrared light.And they can effectively oxided the lactic acid to generate pyruvate and achieve the purpose of terminating the energy supply in the tumor cells.In addition,the expression of HIF-1α,Glut-1 and LDH-A in tumor cells were significantly inhibited,and showing common antitumor activities of both manganese complex and CuS.Therefore,we speculate that Mn-CuS@BSA-FA can become a new type of optical treatment reagent with water as oxygen source and 808 nm laser as light source,and this is the firstly report that this novel Mn-CuS@BSA-FA nanoparticles are active for oxidizing lactic acid to inhibite tumor cells in photocatalytic/water system.