Study On Preparation And Their Antitumor Properties Of Nanodrugs Based On Dendrimer And Polyethyleneimine

At present,chemotherapy and light phototherapy are the main methods of treating cancer.However,most chemotherapy drugs and photosensitizers have defects such as poor water solubility,short blood circulation time,and low tumor targeting.The construction of biocompatible nanodrug carrier is the main method to solve the above defects of small molecule drugs.Zwitterionic materials have strong hydrophilic capacity through electrostatic hydration,which is an important method to improve the biocompatibility of nanodrugs.In this paper,generation five poly?amide amine?dendrimer?G5 PAMAM?and polyethyleneimine?PEI?were used to deliver small molecule drugs,and highly biocompatible nanodrugs were prepared based on the surface modification of G5 PAMAM and PEI using zwitterionic materials.The preparation of nanodrugs,blood circulation time and anti-tumor properties were studied.The specific research contents are as follows:?1?In order overcome the problems of poor water solubility and low bioavailability of chlorin e6?Ce6?,G5 PAMAM was modified by zwitterionic materials and paclitaxel on its surface,and contained Ce6 in its internal cavity to prepare nanodrug G5MPC-Ce6 in chapter 2.Results showed that the nanodrug G5MPC-Ce6 did not induce the aggregation of fibrinogen after incubation and had good protein stability.More importantly,G5MPC-Ce6 had good anti-tumor effect in mice after laser irradiation.?2?In order to improve the blood circulation time and anti-tumor properties of nanodrugs in the body,G5 PAMAM was modified by zwitterionic material carboxybetaine methacrylamide?CBMAA?on its surface to prepare zwitterionic dendrimer?G5-CBMAA_n?in chapter 3.Results showed that G5-CBMAA₃₀ had the longest blood circulation time due to its thickest zwitterionic layer.Nanodrug G5-CBMAA₃₀-ICG was prepared by contained indocyanine green?ICG?in G5-CBMAA₃₀ hydrophobic cavity.Experiments showed that G5-CBMAA₃₀-ICG had better tumor targeting ability and anti-tumor effect than free ICG in mice after laser irradiation.?3?In order to overcome the difficulty of releasing small molecule drugs for dendrimers,amphiphilicity molecule was synthesized with zwitterionic linear PEI as the hydrophilic segment and mercapto-paclitaxel as the hydrophobic segment,and contained doxorubicin?DOX?to prepare drug-loaded micelles?PMPC-DOX?in chapter 4.PMPC-DOX had hydrodynamic size of 137.1 nm and achieved controlled release of DOX in weak acid environment.More importantly,PMPC-DOX showed excellent anti-tumor effect in vivo and vitro.The distribution experiments in mice also showed that PMPC-DOX had better targeting ability to tumor than free DOX.