Preparation Of Functional Composite Particles Based On Polydopamine And Its Application In Cell Fluorescence/Raman Imaging

Fluorescence imaging is one of the most widely used methods due its merits of high-speed acquirement,ease of manipulation and direct observation.Compared with fluorescence method,Surface-Enhanced Raman Scattering(SERS)owns its advantages,including high stability under exposure to photo and super sensitivity.Moreover,SERS imaging can provide abundant vibrational information of molecules to mark specific molecules and monitor their changes.Accordingly,multifunctional particles can be prepared by integrating the merit of fluorescence and Raman signal into composite nanoparticles for multimodal imaging.Research of matrix and template,SERS substrate and probe molecules is of great significance on the construction of SERS/Fluorescence composite nanoparticles.In this work,taking full advantage of the reactivity,adhesiveness and adsorption of polydopamine(PDA)spheres,we designed a series of novel composite nanoparticles with fluorescence/SERS signals.Those particles could be applied in fluorescence and SERS imaging under appropriate laser excitation.Furthermore,to investigate the targeting performance and therapeutic effect of the composite nanoparticles,transferrin(Tf)is conjugated on the surfaces the pH-sensitive drug-loaded functional composite nanoparticles.Our experimental results show that the presented functional composite nanoparticles exhibit a pH-controllable releasing ability and possesses a good targeting ability for tumor cells.The research contents are as follows in detial:Part 1.Herein,we report the fabrication of optimal gold/polydopamine-Methylene Blue(Au/PDA-MB)composite particles for fluorescence(FL)and surface-enhanced Raman scattering(SERS)dual-modal imaging.PDA spheres played an important role in gold ion reduction,gold nanoparticle(AuNPs)binding and MB adsorption,MB were employed as both fluorescence label and Raman reporter.The versatility of PDA and MB makes the particle fabrication very simple and easy.The SERS and FL performances of Au/PDA substrate are optimized by tuning the mass of gold precursor and the reaction temperature.SERS and FL imaging capacity of the Au/PDA-MB NPs are tested on colorectal carcinoma cells(HT-29 cells).Their excellent biocompatibility is demonstrated by low cytotoxicity against HT-29 cells.Part 2.In this part,we developed a simple and versatile method to fabricate gold/polydopamine-Methylene Blue@ Bovine Serum Albumin-glutaraldehyde-Transferrin composite particles(Au/PDA-MB@BSA-GA-Tf NPs)for tumor cell targeting and fluorescence(FL)/ surface-enhanced Raman scattering(SERS)dual-modal imaging.Based on Au/PDA-MB NPs,glutaraldehyde(GA)crosslinked bovine serum albumin(BSA)in the outer layer of Au/PDA-MB nanoparticles can prevent MB from dissociation and leakage.In the bases of the former work,the composite nanoparticles were further modified with transferrin(Tf)to target transferrin receptor(TfR)-overexpressed cancer cells.The targeting ability as well as the intracellular distribution of the composite particles was investigated through SERS/fluorescence imaging.Their excellent biocompatibility was demonstrated by low cytotoxicity against breast cancer cell(4T1 cell).Part 3.In this part,we report the fabrication of the gold/ polydopamine-(Methylene Blue/ doxorubicin)@ Bovine Serum Albumin–glutaraldehyde–Transferrin composite particles(Au/PDA-(MB/DOX)@BSA-GA-Tf NPs)for tumor cell targeting,fluorescence(FL)/ surface-enhanced Raman scattering(SERS)dual-modal imaging and pH-responsive drug release.The composite particles were further endowed with the function of drug delivery.DOX is a common anti-cancer drug,and the drug could release with a large quantity in acidic environment.The anti-cancer drug DOX and Raman probe MB were loaded on Au/PDA substrate simultaneously.Our experimental results show that an increased amount of DOX release was observed at lower pH value.In addition,the composite nanoparticles were conjugated with transferrin(Tf)to target transferrin receptor(TfR)-overexpressed cancer cells.The targeting ability as well as the intracellular location of the dual-modal imaging composite nanoparticles was monitored by SERS mapping while the distribution of DOX was investigated through fluorescence images.The results show that the composite nanoparticles can simultaneously fulfill pH-responsive drug release,SERS-traceable characteristics and cancer cells targeting,which has a unique potential for the target theranostic nanosystems.