Molecular engineering of organic small-molecule photothermal agents by changing the donor group for photothermal therapy and photoacoustic imaging of tumors

Abstract

Photothermal therapy (PTT) and photoacoustic imaging (PAI) have recently gained considerable attention because they are non-invasive therapeutic and diagnostic methods, respectively. However, the efficiency of existing PTT agents is a major limitation that has hindered their further development. In this study, we designed a series of PTT agents (PTA-1–3) based on “D–π–A”-type chromophores with different electron-donating groups, which was aimed at tuning the absorption wavelength and absorption coefficient of the chromophores, and further optimizing the photothermal performance at 808 nm. These hydrophobic chromophores were encapsulated into the hydrogel through nanoprecipitation and finally decorated with a functional peptide to promote their dispersion into aqueous solutions for tumor-targeting in vivo. Compared with PTA-1-cRGD and PTA-3-cRGD, PTA-2-cRGD possessed a better photothermal performance, which can be attributed to its high photothermal conversion efficiency and loading rate. While treating tumors with these PTAs in vivo, PTA-2-cRGD also reached a higher temperature, which enabled it to completely treat the tumor without recurrence. The improved photothermal performance of PTA-2-cRGD also resulted in strengthening of the photoacoustic signal, which was further applied to conduct the PAI of SKOV-3 tumors in vivo. Therefore, we developed an effective agent (PTA-2-cRGD) that can serve as an efficient PAI-guided PTT agent for application in tumor theragnostics.