Construction Of Tumor Microenvironment-responsive Nano-smart Drug Carrier For Cancer Therapy

Currently,conventional chemotherapy,is one of the mainmeans of treatment that is being extensively used by medical professionals in healthcare centers to treat cancer.This form of treatment can cause side effects when systemic administration of drugs is used.Polymer nanomaterials possess numerous special properties,for example it elevates the solubility of hydrophobic drugs and prolongs the duration of drugs in plasma and tissue.The drugs are administered directly on tumor sites and this way reduces the occurring of side effect due to the enhanced permeability and retention effects.Therefore,much attention and research has been focused on anticancer drug delivery by polymeric micelle.Moreover,the tumor microenvironment is made up of numerious charecteristics such as,hypoxia environment,lower pH and affluent oxidants and reducers.Generally,drugs can be dispenced through nano-micelle drug delivery systems via the disintegration of micelle or the cleavage of the responsive chemical bonds,which is stimulated by lower pH with high concentration of glutathione or reactive oxygen species.This thesis was constructed based on sufficient references and main contents.The onclusion is as follows:1)The dual reducing and pH-sensitive amphiphilic micelle nanostructure was synthesised by the maltoheptaose（MH）derivates whch were used as the hydrophilic block and acetylated maltoheptaose（AcMH）served as hydrophobic partment.Then,the amphiphilic MH-S-S-AcMH was constructed through the incorporation of hydrophilic block MH and hydrophobic block N₃-AcMH by propargylcystamine.Afterward the anticancer drug doxorubicin（DOX）was loaded into the micelle formed from the self-assembly of MH-S-S-AcMH.The DOX was then released to kill tumor cell when the polymeric micelle was stimulated by the weak acid environment with high glutathione.2)Two block polymer mPEG-AcMH and PAsp-AcMH were generated from this procedure,and there is possibility chlormethine could be absorbed by PAsp-AcMH.Furthermore,β-lap can be loaded into the micelle derived from self-assembly of m PEG-Ac MH and PAsp-AcMH.β-lap can be released from the disintegration of micelle in a weak acid conditions.Additionally,hydrogen peroxide was acquired after a series of biochemical reactions.Chlormethine molecule was exposed to kill tumor cell when the prodrug chlormethine was oxidized by H₂O₂.