Construction Of Biodegradable Core Cross-linked Nanoparticles From Near Infrared Dyes Encoded Polyprodrug Amphiphiles And Synergistic Anticancer Investigation

It has been widely accepted that covalently framed nanoparticles showed extended circulation time in the blood due to their large stable structures compared to the free linear polyprodrugs.Herein,an efficient method,combining living radical polymerization,ring-opening reaction,and copper(I)catalyzed azide-alkyne cycloaddition click reaction,was employed to prepare amphiphilic polyprodrugs with reduction-responsive camptothecin(CPT)prodrug and photothermal converted nearinfrared dyes(IR780).The drug content could be regulated as needed through the monomer feed ratio.The obtained amphiphilic P[CPTM-co-GMA(-IR780/-OH)]-bPOEGMA polyprodrugs could molecularly dissolve in good solvent and self-assembled into nanoparticles consisting of thiol-responsive P[CPTM-co-GMA(-IR780/-OH)] cores and well-solvated POEGMA coronas in selected solvent.Cross-linking of the P[CPTMco-GMA(-IR780/-OH)] cores could be facilely achieved via the reaction between residual hydroxyls and hexachlorocyclic-triphosphonitrile(HCCP;acid sensitive and biodegradable)to form structural stable core cross-linked nanoparticles.DLS,TEM,UV-vis and fluorescent techniques,as well as subsequent in vitro cell experiments confirmed these CCL nanoparticles possessed excellent aqueous stability,high tumor micromilieu sensitivity,controlled drug release,and severe cytotoxicity to He La cells with the aid of near-infrared light irradiation.Not only that,these CCL nanoparticles could be served as a nanocarrier to load other anti-cancer drugs(curcumin)to realize synergistic and highly effective treatment.Overall,this work provides a convenient way that promise for intelligent responsive and enhancement of anticancer therapy.