Design,Synthesis And Application Of Responsive Fluorescent Polymer Nanoparticles

Recently,thanks to their excellent properties including easy modification and functionalization,easy preparation,suitable water solubility,favorable biocompatibility and low cytotoxicity,responsive fluorescent polymer nanoparticles have been widely applied in biosensing,drug delivery systems,anti-counterfeiting and data encryption and so on.Thus,in this paper,six responsive fluorescent polymer nanoparticles were designed and synthesized as fluorescence probes for the highly sensitive and selective detection of biological marker?Hypochlorous acid:HClO,Glutathione:GSH?and photoswitchable fluorescent nanosystems?PFN?for specific cancer cell marking,rewritable fluorescent imaging in cell,anti-counterfeiting,data encryption and the regulation of multi-color fluorescence performance via multi-means.The main contents and the results of this paper are as following:?1?We prepared fluorescence resonance energy transfer?FRET?-based fluorescent polymer dots?FPD?for the ratiometric imaging of lysosomal HClO in living cells via a simple co-precipitation method.The FRET-based FPD are composed of poly{2,7-?9,9-dihexylfluorene?-alt-2,5-[?thiophen-3-yl?-5-?4-?octyloxy?phenyl?-1,3,4-oxadiaz ole]}?PTPO,donor?and rhodamine B isothiocyanate?RBITC?linked amphiphilic copolymer PEO113-b-P?AEMH5-co-AEMR3-co-St25?.Upon addition of HClO,the fluorescence of RBITC can be quenched and subsequently disturb the FRET process within them,resulting in the ratiometric detection of HClO.The as-prepared FPD with excellent good biocompatibility was successfully used to the ratiometric imaging of lysosomal HClO in living HeLa cells.?2?Reversible addition-fragmentation chain transfer radical polymerization?RAFT?polymerization is used to synthesize the needed amphiphilic diblock copolymer PEO₁₁₃-b-P(St₂₀-co-NPAI₃)with containing of 1,8-naphthalimide?HClO-specific recognition fluorophore,NPAI?.Furthermore,polymer micelles-based ratiometric fluorescent probe?PM?based on the combination of intramolecular charge transfer?ICT?mechanism and FRET principle for selective visualization of endogenous HClO in vivo were developed via co-precipitation strategy.In the presence of HClO,the thiourea moiety,serves as electron-donating group at the 4-position of 1,8-naphthalimide,is easily oxidized and transformed into an electronwithdrawing group?imidazoline moiety?,resulting in a dramatic blue shift??100 nm?in the fluorescence emission due to ICT and FRET.Thanks to the excellent biocompatibility of PM,we have also demonstrated that this probe for endogenous HClO detection in zebrafish model with LPS induces acute liver injury.?3?RAFT polymerization and grafting technology?amidation reaction?was employed to synthesize the needed amphiphilic diblock copolymer PEO113-b-P?AEFA2-co-AEMH9-co-St25?with containing of folic acid?tumor-targeting?.Aggregation-induced emission dots?AIED?were further developed via co-precipitation strategy.By the combination of photostable AIED and MnO₂ nanosheets?GSH response agent?,FRET-based photostable aggregation-induced emission dots?AIED-MnO₂?with tumor-and lysosome-targeting was successfully prepared via electrostatic interaction.The fluorescence of AIED was effectively inhibited due to the MnO₂ nanosheets with the capability of broad-spectrum quenching.However,the introduction of GSH could reduce MnO₂ into Mn²⁺and trigger the remarkable enhancement of the fluorescence of the nanoprobe.Furthermore,the as-prepared AIED-MnO₂ with excellent biocompatibility was successfully utilized to imaging and detecting endogenous GSH in lysosomes in FA-positive HeLa cell.?4?Amphiphilic diblock copolymer[Gal-PEGMA₆₁-b-P(St₂₄₄-co-SP₆)]was firstly prepared via combining RAFT and click reaction.By employed4,7-bis?4-?1,2,2-triphenylvinyl?phenyl?benzo[c][1,2,5]thiadiazole?BTPEBT?with two-photon excitation?TPE?as donor,photoswitchable AIE dots?PAIED?were obtained via a simple co-precipitation method.The introduction of AIE fluorophors with TPE could effectively avoids some problems including ACQ and small tissue-penetration depths.In adition,the as-prepared PAIED shown some excellent performance including reversible photoisomerization property,high FRET efficiency and excellent stability.Hence,based on the above excellent photoswitchable performance,the as-prepared PAIED were successfully applied in data storage and information encryption.Thanks to the targeting ability of liver cells,PAIED could perform potential application in the rewritable dual-color imaging in liver cells.?5?By combining 9-?diethylamino?-5-oxo-5H-benzo[a]phenoxazin-2-yl-methacrylate?NRME,donor?and 2-?3,3-dimethyl-6'-nitrospiro[indoline-2,2'-thiochromen]-1-yl?ethyl methacrylate?STPMA,acceptor?,photoswitchable red fluorescent polymeric nanoparticles were synthesized by a one-pot miniemulsion polymerization.Because of the excellent perfpormance of nanoparticles,it is benefit to appliy in data encryption,anti-counterfeiting,and intracellular reversible fluorescence imaging.Thanks to the excellent biocompatibility of nanoparticles including favorable biocompatibility and low cytotoxicity,PFPNs can be successfully applied in reversible fluorescent image in HeLa cell.In addition,PMMA and PMA were choosed as carrier material to help construct superior photoswitchable materials for data encryption and anti-counterfeiting.The above results indicated that PFPNs has a wide application prospect in data encryption,anti-counterfeiting and intracellular reversible fluorescence imaging.?6?We have developed a class of FRET-based SFPNs via scalable miniemulsion polymerization that are able to generate stable white light in single particles by embedding SPMA and p-DTPACO together.In a rational design of transfer efficiency,a stable white-light emission is obtained.Both light and solvent were used to switch the white light to other color emissions including cyan and pink by regulating the FRET efficiency.These SFPNs show high-contrast fluorescence,fast photoresponsibility,outstanding photo-reversibility,and excellent long-term stability.Such multi-color fluorescent alternation is reversible and therefore allows for data encryption.Conclusively,we are focusing on the design and synthesis responsive fluorescent polymer nanoparticles to solve the bottle-necks in small-molecular fluorescent probes and photochromic compounds,and then further expand its application.