NIR-controlled HSP90 inhibitor release from hollow mesoporous nanocarbon for synergistic tumor photothermal therapy guided by photoacoustic imaging

Photothermal therapy (PTT) has been widely studied for tumor therapy. However, the clinical transformation of PTT has encountered significant challenges in tumor recurrence, because the uneven hyperthermia in tumor tissues can result in the survival of cancer cells in the lower temperature regions close to blood vessels (as the blood flow can dissipate the localized heat). It is therefore important for clinical treatments to retain the excellent therapeutic efficiency of PTT at relatively low temperatures. In this article, innocuous hollow mesoporous carbon spheres (HMCS) with a high photothermal conversion efficiency were obtained by a one-pot synthesis method. After modification with DSPE-PEG, the HMCS-PEG exhibited a superior stability in biomedia, which is beneficial for further biological applications. Interestingly, combined with hydrophobic gambogic acid (GA) which can downregulate heat shock protein 90 (HSP90), the HMCS-PEG-GA system showed a significant NIR-enhanced tumor therapeutic effectin vitroandin vivounder mild temperature conditions (similar to 43 degrees C), and the combination index (CI) value of HMCS-PEG-GA was found to be 0.72. Meanwhile, this nano-system possessed good photothermal imaging and photoacoustic imaging abilities. Guided by the photoacoustic imaging signal, HMCS-PEG-GA showed enormous potential for use in accurate tumor diagnosis and mild-temperature PPT treatment applications, which is very important for clinical transformation of this nano-system.