Preparation Of Polyphosphoester Based Nanoparticles For Drug Delivery And Photothermal Therapy

Photothermal therapy?PTT?as a new development of minimal invasiveness cancer therapy,the antitumor effect is largely dependent on photothermal transducers.Inorganic PTT agents have the advantages of simple preparation progress and material easy obtaining,but those nanomaterials exhibited low photothermal conversion efficiency and remain inside the body for very long periods of time,which could result in potential long-term toxicity.Organic small molecular dyes have good biocompatibility but the low photothermal stability limit their future application.Therefore,development of efficient photothermal agents with good biocompatibility,excellent photostabiliy and high photothermal conversion efficiency is still highly desirable.The main contents and results of this dissertation are described in two parts as below:1.We have prepared conjugated polymers PBIBDF-BT with alternating isoindigo derivative?BIBDF?and bithiophene?BT?,which exhibited strong near-infrared?NIR?absorbance due to its low band gap?1.52 eV?and could be suitable for photothermal therapy.To stabilize the hydrophobic conjugated polymer in physiological environments,we utilized an amphiphilic copolymer,mPEG-b-PHEP to stabilize PBIBDF-BT-based nanoparticles(PBIBDF-BT@NP_PPE)through a single emulsion method.The obtained nanoparticles PBIBDF-BT@NP_PPE showed great stability in physiological environments and excellent photostability.Moreover,the PBIBDF-BT@NP_PPE exhibited high photothermal conversion efficiency,reaching 46.7%,which is relatively high compared with those of commonly used materials for photothermal therapy.Accordingly,in vivo and in vitro experiments demonstrated that PBIBDF-BT@NP_PPE exhibits efficient photothermal anticancer efficacy.More importantly,PBIBDF-BT@NP_PPE could simultaneously encapsulate other types of therapeutic agents though hydrophobic interactions with the PHEP core and achieve NIR-triggered intracellular drug release and a synergistic combination therapy of thermo-chemotherapy for the treatment of cancer.2.In the previous chapter,we have reported donor-acceptor conjugated polymers?CPs?had robust absorbance in nearinfrared?NIR?region,great photostability,high photothermal conversion efficiency,and good biocompatibility.Thus,the CPs exhibited great potentials as the contrast agent for photothermal therapy?PTT?and photoacoustic imaging?PAI?.However,poor understanding of the underlying mechanisms and the correlation between the CP polymer chemical structure and its performance of PTT and PAI has significantly hindered its biomedical application.Thus,a series of acceptor–?–acceptor type?A1–?–A2?type CPs were synthesized.The diketopyrrolopyrrole?DPP?and thiophene are used as A1 electron accepting block and ?-bridge,and the chemical structure of A2 unit was variable.The CPs were formulated into PEGylated nanoparticles with the assist of an amphiphilic copolymer?mPEG-b-PHEP?,which ensured these CP-based nanoparticles?CP@NPs?exhibited similar size,shape,and physiological stability.Thus,the chemical structure of A2 unit was the only variable.The effects of the CP chemical structure are carefully and comprehensively evaluated through both in vitro and in vivo experiments.Our results demonstrated the chemical structure of A2 unit simultaneously impact their absorption spectra and photothermal?PT?conversion efficiency,which finally determined their PTT and PAI performances.