Polydopamine Increaseing Capacity Of Albumin Nanoparticles For Photothermal Gene Synergistic Tumor Therapy

As one of the most deadly diseases in the world today,cancer is a great threat to human health.However,the clinical results show that,due to the diversity and complexity of human tumors,monotherapies are easy to make the cell resistance,and it is difficult to eliminate the tumor completely.In order to overcome the limitation,the multi-modal therapies are extensively developed by the design of nano-platforms,which can not only enhance the therapeutic effect but also achieve an anti-tumor effect at a lower drug dose to reduce side effects.The heat generated by photother mal therapy(PTT)leads to the overexpression of heat shock protein(HSP)in tumor cells,which undermines the effect of therapy.Thus,the therapeutic effect of PTT can be enhanced by gene regulation to inhibit HSP expression.At the same time,the bio-stability,the cellular uptake,and the endosome escape of the therapeutic nucleic acids can also be enhanced by the combination with PTT nano-materials.Compared with the inorganic counterpart,the organic PTT nano-materials show better biocompatibility and low long-term toxicity.However,the poor photostability and the lack of an efficient functionalization method limit their clinical applications.Based on the above discussion,this dissertation developed an all-organic nanoplatform for synergestic therapy of PTT and gene-regulation.Specifically,IR780 was selected as the organic PTT agent an d a HSP70-silencing small interfering RNA(si RNA)was optimized for gene-regulation.Polydopamine(PDA)was selected as the interlayer.First,the hydrophobic organic dye,IR780,was encapsulated by bovine serum albumin(BSA)through hydrophobic interaction to form water-dispersible nanoparticles.Then by solution oxidation method,dopamine can form a PDA coating layer on the surface of IR780/BSA nanoparticles.We demonstrated that the PDA layer could significantly enhance the photostability of IR780,and the PTT efficiency was also highly improved due to the photothermal effect of PDA.Meanwhile,a high density of catechol groups on the surface of PDA layer facilitated the efficient and controllable graft with si RNAs by Michael addition reaction.Due to the “cluster” effect of the high-density si RNAs on the surface,the bio-stability and cell transfection efficiency of si RNAs were significantly enhanced.In the in vitro cell experiment of human lung adenocarcinoma A549 cell,cell killing efficiency over 36% was achived during the synergistic therapy,which is obviously higher than the cell killing efficiency under single photothermal therapy method,which is about 28%.These results shown that the RPBIR nanoparticles prepared by the introducing of PDA realized synergistic therapy between photothermal and gene based on organic photothermal conversion agent,and shown a significantly better therapeutic effect than any monotherapy,providing a new idea for photothermal-gene synergistic therapy.