Amphiphilic Polymer-mediated Controllable Self-assembly Of Luminescent Gold Nanoparticles And Their Tumor Targeting

The ultrasmall luminescent gold nanoparticles?Au NPs,d<3 nm?with unique optical properties,easy surface modification and good biocompatibility are extremely useful in the fields of sensing,bioimaging,and disease diagnosis.Such particle sizes smaller than 6 nm could be quickly eliminated from the urinary system,which could guarantee the nanoparticale are safety to the body.However,short blood circulation will cause low targeting efficiency.The amphiphilic block copolymers?ABC?could self-assemble into distinguished core-shell nanoarchitectures in solution,serving as a carrier for clinical hydrophobic anticancer drugs,such as doxorubicin and paclitaxel.The hydrophobic drugs coated in the micelle core are protected by the outer hydrophilic PEO layer,which avoid the elimination by the liver and spleen,and prolong the blood circulation for high targeting efficiency.The self-assembly of the Au NAs with adjustable emission wavelength,controllable morphology and loadage are highly desired but still remains challenge.In addition,the behavior of Au NAs in-vivo is still unknown.Based on the bottom-up method,we demonstrated a straightforward strategy to in situ fabricate three Au NAs with highly controllable emission wavelength,shape and loadage of Au NPs by just regulating the reductant in the growth of ultrasmall luminescent Au NPs with amphiphilic block copolymers pluronic F127 as template.The formation mechanism and influencing factors of the three Au NAs were systematically investigated through a series of experiments.The reductants including tetrakis?hydroxymethyl?phosphonium chloride?THPC?,dimethylamine borane?DMAB?and sodium borohydride?Na BH₄?,with different reducing abilities,adjusted the coated Au NPs with different amount of Au?I?species,which not only changed the emissions of the Au NAs,but also adjusted the hydrophobic/hydrophilic environment of the micelles in turn to control the morphology and loadage of Au NP in Au NAs.Besides the luminescent Au NAs prepared above,the Au NAs with loaded Au NPs diameters of 5 nm and 12 nm?5nm-Au NAs,12nm-Au NAs?were prepared by ligand exchange reaction to further investigate loadage would affect the behaviour in the biological process.Through carrying out a series of experiment such as protein absorption test,cytotoxicity,cellular uptakes,pharmacokinetics,biodistribution and in-vivo imaging on Au NAs with different morphology and loadage,we found that the protein adsorption capacity,blood circulation time and targeting efficiency were all related to its morphology and loadage.The results unambiguously demonstrated that the high targeting efficiency of Au NAs could be achieved with controllable shape and loadage by facilely regulating the reducing agents.