Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment

Abstract

Background The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy. Results A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza–boron–dipyrromethene (aza-BODIPY) dyes with donor–acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity. Conclusions Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.

Near-infrared absorbing aza-BODIPYs with 1,7-di-tert-butyl groups by low-barrier rotation for photothermal application

“…Then, the photothermal conversion efficiency of S-tBuazaBDP-NPs was calculated to be 49%, and was near to the highest one (50.5%) in aza-BODIPY system. 81 Next, in order to evaluate S-tBuazaBDP-NPs photothermal stability, we used 690 nm laser (0.8 W•cm -2 ) to irradiate dyes in aqueous solution (80 M) for 5 min, then cooling naturally, and the temperature changes were recorded during the process of heating-cooling cycles. As shown in Fig.…”

An aza-BODIPY-based NIR-II luminogen enables efficient phototheranostics

“…CB1 is fairly hydrophobic as are many other NIR-II fluorophores 32 and therefore DSPE-PEGylated CB1 nanoparticles were prepared by a nanoprecipitation approach. The morphology of the CB1 NPs was characterized by TEM and SEM.…”

“…[25][26][27][28] However, few of them exhibit NIR-II emission capabilities. [29][30][31][32] Herein, we report the design and preparation of a new aza-BODIPY-derived agent named CB1 with extended π-conjugation and proper structural modifications (Scheme 1). The DSPE-PEGylated CB1 nanoparticles (CB1 NPs) show a maximum emission peak at 1015 nm and are capable of in vivo NIR-II fluorescence imaging.…”

Stable twisted conformation aza-BODIPY NIR-II fluorescent nanoparticles with ultra-large Stokes shift for imaging-guided phototherapy

“…26 Subsequently, several NIR-II aza-BODIPY fluorophores were acquired, but their fluorescence was too weak to carry out NIR-II fluorescence imaging after the photosensitizers were encapsulated into nanoparticles. 27,28 In addition, the efficiency of PDT or PTT alone is usually unsatisfactory because of the hypoxic nature of the tumor microenvironment for PDT and acquired a heat shock effect in PTT. 29 The collaboration of PTT and PDT is a good strategy to overcome the respective drawbacks to enhance treatment output because PTT could improve the oxygen supply in the tumor tissue by increasing the blood flow rate, thus promoting the PDT effect, which conversely further eliminates the heat-resistant tumor cells in PTT.…”