ATP Inhibition for Starvation/Mild Photothermal/Photodynamic Synergy Therapy Using Polypeptide Nanoparticles Conjugating 2‐Deoxy‐D‐Glucose and Dye under NIR Phototheranostic Strategy

Abstract Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down‐regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2‐deoxy‐D‐glucose (2DG) is an anti‐glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low‐temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx‐BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as‐prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR‐I/II fluorescence imaging‐guided starvation/MPTT/PDT synergy therapy for tumors.