The Preparation Of Hyperbranched Poly(amino-ester)s And Star Copolymer Unimolecular Nanomedicine

Nanomedicine can achieve targeted delivery of drugs,reduce the side effects of drugs,and present a good therapeutic effect.Hyperbranched polymers are an excellent nano drug carrier due to their unique molecular structure and physicochemical properties.In this thesis,a novel type of hyperbranched poly?amino-ester?s?HBPAE?with both surface and interior containing functional moieties were designed and synthesized.These hyperbranched poly?amino-ester?s were modified as multifunctional hyperbranched star copolymers-based nanodevices,and the antitumor effect of hyperbranched star copolymers-based nanodevices was carefully studied The specific research work is divided into the following two parts:?1?A series of RB'B₂ branched monomers?R:hydroxyl,alkene,alkyne;B':primary amine,B:secondary amine?are prepared by ring-opening reaction of epoxy compound and ethylenediamine.Hyperbranched poly?amino ester?s with the surface containing acrylate bonds,backbone containing polyethylene glycol?PEG?,and interior containing R?R:hydroxyl,alkene,alkyne?have been one-step synthesized via the michael addition polymerization of A₂-type monomer and RB'B₂-type monomer.The polymerization kinetics and influencing factors of hyperbranched poly?amino ester?s were carefully studied by using polyethylene glycol diacrylate as A₂-type monomer and commercial N-ethylethylenediamine as B'B₂-type monomer.The hyperbranched poly?amino-ester?s with narrow molecular weight distribution,fast polymerization rate and high polymerization degree can be prepared by controlling the molar ratio of A₂ and B'B₂ to 2:1,the reaction temperature to 80oC,the reaction solvent to ethanol,and the reaction time to 24 h.The series of hyperbranched poly?amino ester?s have a highly branched structure,the Mark-Houwink parameter?was all lower than 0.5,the molecular weight distribution was all narrow?PDI=1.30¹.50?,and the Tg was between-42 ^oC and-39^oC.The hyperbranched poly?amino ester?was modified with imidazole by michael addition reaction of acrylate in HBPAE and amine in imidazole.It demonstrated the possibility of functional modification of the terminal group,and the hyperbranched poly?amino ester?s showed good water solubility and pH responsive.?2?The surface of these hyperbranched polymers were then modified with poly?ethylene glycol?chains,and their interior branching units R?R:hydroxyl,alkyne?were functionalized with anti-cancer drugs doxorubicin through acid-sensitive hydrazone or cisplatin through coordination,resulting a multifunctional hyperbranched star copolymer unimolecular nanomedicine?HBPAE-Ahz-DOX-PEG,HBPAE-COOPt-PEG?.The drug loading capacity of HBPAE-Ahz-DOX-PEG and HBPAE-COOPt-PEG were 32.0%and 27.2%,respectively.In aqueous solution,HBPAE-Ahz-DOX-PEG can form single-molecule micelles with the particle size of 16²0 nm,and HBPAE-COOPt-PEG can form single-molecule micelles with the particle size of 30³4 nm.Since the drug molecules were conjugated into the internal backbones of the hyperbranched poly?amino ester?s,these hyperbranched star copolymers-based nanodevices showed good drug loading capacity and unimolecular stability.These unimolecular nanomedicines also exhibited intracellular pH-responsive drug release behavior and good in vitro anti-tumor effects,making them promising candidates for drug delivery and tumor therapy.