pH-responsive Ag₂S nanodots loaded with heat shock protein 70 inhibitor for photoacoustic imaging-guided photothermal cancer therapy.

Abstract

Heat-treated cancer cells have thermo-resistance due to the up-regulated levels of heat shock proteins (HSP) resulting in low therapeutic efficiency and ineffective ablation of tumors. In this work, we report pH-responsive Ag₂S nanodots (Ag₂S NDs) loaded with HSP70 inhibitor (QE-PEG-Ag₂S) for enhanced photothermal cancer therapy. QE-PEG-Ag₂S was easily prepared via self-assembly of hydrophobic Ag₂S NDs, amphiphilic pH-responsive PEG_5k-PAE_10k polymer, and an HSP70 inhibitor quercetin (QE). QE-PEG-Ag₂S has ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The slightly acidic environment of tumor cells and the acidity of lysosomes as well as the high temperature generated by photothermal therapy under irradiation of NIR light (808 nm) promote the release of the inhibitor molecules to reduce the heat resistance of cancer cells and improve the in vivo photothermal therapy efficiency. Moreover, QE-PEG-Ag₂S has good photoacoustic imaging (PAI) ability; this QE-PEG-Ag₂S concentration dependent signal can precisely follow the accumulation of the nanomaterials in tumors and dictate the correct time for light therapy. As a result, QE-PEG-Ag₂S achieved complete tumor ablation effect with no recurrence when only irradiated with NIR light for 10 min. This approach offers a new approach for the theranostic applications of Ag₂S NDs. STATEMENT OF SIGNIFICANCE: In this work, pH-responsive Ag₂S nanodots loaded with the heat shock protein inhibitor for enhanced photothermal cancer therapy have been simply prepared via self-assembly process. This nanoagent possesses ideal water-solubility and biocompatibility, can rapidly enter cells, and preferentially accumulate in cell lysosomes. The acidic environment of tumor cells and the acidity of lysosomes, as well as the high temperature generated by photothermal therapy under irradiation of NIR light promote the release of the inhibitor molecules from the nanoagent to improve the in vivo photothermal therapy efficiency. Moreover, the photoacoustic imaging (PAI) of the nanoagent can precisely follow the accumulation of the nanomaterials in tumors and dictate the light therapy time to guarantee the complete tumor ablation effect with no recurrence.