6.2.2.1　3D macromolecules

Dendritic polymer is a kind of 3D macromolecule with multilevel branching structure，which is obtained by constantly repeating branched growing from the central molecule.Its size is typically between 5 and 50 nm with good uniformity and can be adjusted precisely.Both interior and surface of dendritic polymer can be designed by various functional groups，which are able to combine with drug molecules through physical or chemical interaction.The drugs combined via physical interaction could be released too fast and are easy to leak，while the drugs combined by chemical interaction are hard to be released.Grafting hydrophilic chains（e.g.，PEG）on the surface of hydrophobic dendritic polymer can improve drug loading and the stability of the physical interaction-combined drugs.Polyamide-amine（PAMAM）is a kind of dendritic polymer nano-drug carrier material that has received a lot of studies.Bhadra et al.found that after grafting PEG on the PAMAM surface，the drug loading of an anticancer drug 5-fluorouracil（5-FU）was increased 12 times，the drug release rate was reduced to 1/6，the circulation time in blood was increased 3 times，and the efficacy is 10 times as much as 5-FU naked medicine.By regulating the surface degree of polymerization and grafting rate of PEG，the drug loading and the release rate of PAMAM could be controlled accurately.In addition，the release of chemical interaction-combined drugs can be improved by chemical bonds that are easy to fracture in the body.For example，drugs connected through ester bond are more likely to be released than via amide bond.More importantly，under the weak acid environment of the tumor，drug molecules can combine with dendritic polymer by the acid sensitive chemical interaction（e.g.，hydrazone bond），which can realize stimulus responsive drug release，improve the cytotoxicity of drugs，and avoid the killing to normal cells.Kono et al.reported that the cytotoxicity of doxorubicin（DOX）bonded on the surface of PAMAM via hydrazone bond is 10 times better than that of drugs through amide bond connection.Similarly，proteins are also 3D macromolecules，and have been widely used as nano-drug carriers.(https://www.daowen.com)