Development And Application Of Polydopamine-Based Nanocarrier And Fluorescent Nanoprobe

As an emerging material,nanomaterials exhibit many excellent properties,such as simple synthesis process,easy surface modification with multiple functions,good biological safety and controllable size.Based on these advantages,nanomaterials have attracted much attention in the fields of energy and environment,materials science and biomedicine.Polydopamine（PDA）,one kind of organic polymer nanomaterials,has the characteristics of good biocompatibility and biodegradability,high light-to-heat conversion efficiency,rich surface functional groups and high adsorbability.Therefore,PDA has broad application prospects in cancer diagnosis and treatment,drug delivery and biological detection.In the current research,polydopamine-based nanomaterials are relatively complicated and the preparation process is relatively cumbersome.In addition,the targeting properties and drug loading capabilities should be improved.Therefore,in order to improve the photothermal therapeutic efficacy of PDA on the malignant tumors,it is feasible to prepare highly targeted PDA,which can be used as a drug delivery platform during photothermal therapy.Besides,PDA with the proper size has fluorescence properties,which is expected to be used for the detection and imaging of key intracellular small molecules,so as to tracing the tumor treatment process of the tumor.So far,there are relatively few reports on the use of fluorescent PDA for biological detection and imaging,and the luminescence mechanism and detection principle of PDA need to be further explored.In view of this,it is of great significance to construct a new type of fluorescent nanoprobe based on PDA and use for the detection of small molecules in living cells.Based on this,this paper mainly studies the following two aspects:1.In the second chapter,a nanoplatform based on PDA nanocomposites is constructed for the delivery of autophagy inhibitors,to study the role of inhibiting autophagy in tumor photothermal therapy.Firstly,PDA nanoparticles are synthesized.In order to improve the targeting ability of nanocarriers to tumor cells,polyethylene glycol（PEG）modified with folic acid（FA）and galactoside（Gal）is attached to the surface of PDA nanoparticles.Besides,PDA modified with Rhodamine B（Rh B）is also used for real-time tracking and imaging the treatment in vivo and in vitro.Then,the autophagy inhibitor chloroquine（CQ）is loaded on the surface of the nanocarrier PDA-PEG-Rh B/FA/Gal（PPRFG）through theπ-πstacking interaction.Results show that the nanocarrier PPRFG exhibits good biocompatibility,low cytotoxicity,certain drug loading capacity and high photothermal conversion efficiency.During photothermal therapy,the thermal effect of PPRGF could cause protective autophagy in tumor cells,which restricts the therapeutic effect.However,as PPRFG/CQ is used,the release of CQ under acidic conditions of tumor cells can inhibit this protective autophagy and enhance the effect of photothermal therapy.This has been well verified in vivo experiments.2.In the third chapter,a PDA-based fluorescent nanoprobe is constructed for detecting hydroxyl radicals（·OH）in a simple,rapid and highly selective manner.First,fluorescent polydopamine（F-PDA）nanoparticles are synthesized through the oxidation of dopamine（DA）under alkaline conditions and their size and morphology were characterized.Then the detection of·OH with F-PDA was studied.Results show that the F-PDA nanoprobe possesses stable fluorescence properties(λ_ex=410 nm,λ_em=510 nm).In the range of 0-140μM,the concentration of·OH has a linear relationship with the fluorescence intensity of F-PDA（R²=0.9988）.In addition,common metal ions,amino acids,oxidizing substances and reducing substances do not interfere with the detection of·OH,indicating that F-PDA nanoprobe has good selectivity.More importantly,the F-PDA nanoprobe has low cytotoxicity and has been successfully used for detecting·OH in living cells.The construction of the F-PDA fluorescent nanoprobe provides an idea for the detection of other active species in living cells.