Based On The Self-assembled Structure Of PEG-b-PS And Its Anti-tumor Activity As A Photosensitizer Carrier

Photodynamic therapy?PDT?is a U.S.Food and Drug Administration?FDA?approved cancer treatment modality.The key factors in PDT are photosensitizers?PSs?,light and O₂.PSs can be excited by light with specific wavelength and transfer light energy to O₂ for the generation of cytotoxicity reactive oxygen species?ROS?which can oxidatively damage tumor cells.There is no obvious cytotoxicity without irradiation that means low side effects on normal cells or tissues.Therefore,the PDT treatment has been developed in recent years due to lower physiological toxicity than other cancer therapies.Phthalocyanine,as an excellent PS,attracted much attention because of good biocompatibility and photosensitive antitumor activity.However,there are several deficiencies which limit the anticancer activity of PDT.First of all,the rapid proliferation of tumor cells makes blood vessels abnormal leading to the low content of oxygen in tumor tissues.Furthermore,the concentration of PSs in tumor tissues is a key factor for anticancer activity of PDT so that the tumor targeting character of PSs is also a major problem.Last but not the end,for most classic PSs in PDT treatment,¹O₂ is the crucial one of ROS.However,the lifetime of ¹O₂ is less than 40 ns in biological environment,leading to its limited diffusion range?20?40 nm?which reduce its utilizing efficiency seriously resulting in the reduction of anticancer activity of PDT.In this paper,the regulation of self-assembly of diblock copolymer PEG-b-PS was studied and a nanomotor with magnetic targeting and catalytic capacity of hydrogen peroxide was designed and manufactured to enhance the PDT activity.The specific research contents are as follows:1.There are both hydrophilic and hydrophobic capacity of the amphiphilic block copolymer,PEG-b-PS.The amphiphilic specialty of the PEG-b-PS makes it possible to self-assemble into specific structure in the mixture of cosolvent and selective solvent as familiar as surfactants.These polymers have excellent ability in drug delivering owing to its characteristics of amphiphilic.In this paper,different degree of polymerization of amphiphilic diblock copolymer PEG-b-PS were obtained as raw materials of self-assembly.To summarize the morphology regulation of self-assembly of PEG-b-PS,different variables were chosen including methods of solvent mixing and stirring,solvent mixing rate,environmental temperature,polymerization degree of PEG-b-PS and additions,etc.The morphology and size of self-assembly structure were measured by TEM.The purpose of researches on self-assembly of PEG-b-PS was to manufactured a specific stomatocytes structure whose diameter was about 300 nm for nanomotor preparation.To endow the PSs with characters of magnetic targeting and catalytic capacity of hydrogen peroxide,Fe₃O₄ nanoparticles can be synthesized and loaded in the cavity of stomatocytes structure.Thus,four kinds of Fe₃O₄ nanoparticles were synthesized according to the references and characterized by TEM.To pick a sort of appropriate Fe₃O₄nanoparticles for manufacture of nanomotors,all the nanoparticles were compared with each other by size and dispersion.The most suitable were TEG-modified Fe₃O₄ nanoparticles and the catalytic capacity of teg-modified Fe₃O₄nanoparticles with H₂O₂ was verified.Two kinds of zinc phthalocyanine?Zn Pc?photosensitive drugs were synthesized by DBU liquid phase synthesis method,and the choice of tetra-substituted sodium phthalocyanine was determined by loading situation.2.To overcome the drawback of PDT in tumor treatment,we designed a nanomotor with magnetic targeting ability?iron oxide nanoparticles loaded stomatocytes,denoted IS-NMs?.After the kinetic characteristic of IS-NMs was confirmed,phthalocyanine was loaded on IS-NMs to form a novel composite nanomotor?iron oxide nanoparticles loaded stomatocytes@phthalocyanine nanomotors,denoted ISP-NMs?.And we measured the loading capacity of Zn Pc and TEG-modified Fe₃O₄ nanoparticles.In the aqueous solution of 200?M H₂O₂,the velocity of IS-NMs can reach 1665 nm/s,which is much higher than the Brownian velocity of that 307 nm/s.In vitro cell experiments showed that ISP-NMs could be uptaken effectively by tumor cells and catalyzed the decomposition of H₂O₂ to produce oxygen and promote its movement.The characteristics of magnetic targeting,magnetic resonance and fluorescence imaging and catalytic capacity of hydrogen peroxide were detected.Furthermore,the enhancement of ISP-NMs was measured through experiments of photosensitive antitumor activity in vitro and in vivo.