Author
Chie Kojima, Department of Materials Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, Yokohama, Kanagawa, Japan
Keywords
drug delivery system, dendrimer, surface engineering, stimuli-responsive materials, immune cells, lymph node, cancer therapy
Abstract
Dendrimers are highly branched and well-defined synthetic polymers. Owing to their unique structures, versatile bioactive molecules can be modified onto their end groups and/or encapsulated within dendrimers. Therefore, dendrimers are highly potential as nanocarriers for drug delivery systems (DDS). We have investigated various surface engineered dendrimers to achieve biocompatible and stimuli-responsive functions. For instance, polyethylene glycol (PEG)-grafted polyamidoamine (PAMAM) dendrimers could encapsulate anticancer drugs, photosensitizers, gold nanoparticles and other molecules. PEG-grafted dendrimers, which exhibit prolonged blood retention and accumulation in tumor sites via the enhanced permeability and retention (EPR) effect and could attenuate the anti-PEG immune response. We found the tumor accumulation property is related to their hydration states, which represents a new criterion for designing tumor-targeting nanocarriers. Besides, peptide- and amino acid-modified PAMAM dendrimers have been developed as artificial proteins as well as pH- and thermo-responsive nanoparticles, which could be applicable as dual-responsive DDS and sensing systems. We have also studied dendrimers with anionic terminal groups for specific delivery to lymph nodes. Although various anionic terminal dendrimers accumulated in lymph nodes after intradermal injection, their association with immune cells differed depending on the terminal structures. We successfully achieved delivery to lymph node-resident T cells using anionic terminal phenylalanine (Phe)-modified dendrimers. This review summarizes the potential of dendrimers as functional nanoparticles for DDS and highlights the significance of surface engineering in controlling dendrimers’ biological properties.