Synthesis Of Hyperbranched Polymer Anticancer Drug Carrier With Hydrazone Bond Response

Malignant tumor,commonly known as cancer,has the characteristics of high mortality,strong metastasis,complicated cause and repeated recurrence,which not only brings great pain to patients,but also causes economic burden to the country.At present,cancer has been identified as world’s largest human health killer by World Health Organization(WHO).The most commonly used and effective treatment is chemotherapy in cancer treatments.However,small molecular anticancer drugs used in chemotherapy(such as epirubicin)have some shortcomings,including strong side effects and low bioavailability.In order to solve the above shortcomings,designing drug carriers which can improve the biocompatibility of small molecular anticancer drugs and reduce their side effects is particularly in urgent.Therefore,selecting biological nanomaterials with excellent properties and developing nano-drug carriers with great biocompatibility is core content in this project research,which can prolong internal body circulation.The main content of the study is to determine the performance of nano-drug carriers,simulate its controlled release of small molecular anticancer drugs in vitro and explore its application at the cellular level.In this paper,the outer end of nanomaterials was first modified by hyperbranched polymer shell(prepared by anionic polymerization),and further modified with sites for dynamic binding of small molecules of anticancer drugs(which are composed of p H-sensitive dynamic chemical bonds,such as Hydrazone bonds).This site is stable under alkaline conditions and dissociated under acidic conditions,which perfectly fits the acidic microenvironment of the tumor and achieves passive targeting.This kind of biocompatible and biodegradable drug carrier has a strong competitiveness in the controlled release of antineoplastic drugs.This paper is divided into three parts:Part I:The synthesis and application of hyperbranched polymers were reviewed,and the tumor microenvironment,the classification of anticancer drugs and their development prospects were introduced.Part II:Cellulose nanocrystals(CNCs)were used as the target material.A hyperbranched polymer shell was coated on the surface of cellulose nanocrystals,and hyperbranched polymerized cellulose nanocrystals(CNCs-HPG-HEBA)were obtained.The hyperbranched polymer shell was obtained by anionic ring-opening polymerization of epoxy propanol and hydroxyl groups on the surface of CNCs,and then the terminal group of the hyperbranched polymer shell was modified to the active site.The synthesized products were characterized by transmission electron microscopy(TEM),atomic force microscopy(AFM),and ~1H-NMR,Fourier transform infrared spectroscopy(FT-IR),X-ray diffraction(XRD),dynamic light scattering(DLS),gel chromatography(GPC).Then the release of epirubicin(EPI)was simulated in vitro.Finally,the cytotoxicity of the end product was explored and its physiological activity in the cell was observed by confocal microscope(CLSM).Part III:The target material wasβ-cyclodextrin,modified as hyperbranched polymerβ-CD-HPG-EBA-HH.Usingβ-cyclodextrin as the base,the anionic ring-opening polymerization of propylene oxide was carried out directly on the surface ofβ-cyclodextrin to form a ring-shaped shell on the surface ofβ-cyclodextrin.Then,through the further modification of ethyl bromoacetate and hydrazine hydrate,the end group of the annular shell is modified to hydrazide for the dynamic binding of small molecules of anticancer drugs containing carbon groups.The product was characterized by TEM,FT-IR,~1H-NMR and other technical means.The drug carrier and release experiments were simulated in vitro;then the inhibitory effects of complex(carrier plus drug)and pure drug on HepG2 cells were studied at the cellular level.