Dual-Stimuli-Responsive Polypeptide Nanoparticles for Photothermal and Photodynamic Therapy

We report the assembly of dual-responsive polypeptide nanoparticles loaded with indocyanine green (ICG) using a mesoporous silica (MS) templating method for photothermal and photodynamic therapy. Polypeptide nanoparticles composed of thiol-modified polylysine (PLL) are cross-linked with disulfide bonds and modified with poly(ethylene glycol) (PEG) and pH-sheddable dimethylmaleic anhydride (DMMA), which exhibit reduction- and pH-responsiveness. Cross-linking with disulfide bonds does not influence the free amine groups on PLL chains for further cargo conjugation and surface modification. The stripped DMMA at acidic pH reverses the zeta potential of PLL nanoparticles from negative to positive charge and subsequently results in high cell association. The thermo-responsiveness and singlet oxygen generation of the loaded ICG in DMMA-modified PLL nanoparticles are comparable to those of free ICG under laser irradiation, which induces higher cytotoxicity to cancer cells compared to succinic anhydride (SA)-modified PLL nanoparticles that are not pH-responsive. The reported dual-responsive PLL nanoparticles provide a promising platform for improved photothermal and photodynamic therapy.