Utilizing Intramolecular Photoinduced Electron Transfer to Enhance Photothermal Tumor Treatment of Aza-BODIPY-Based Near-Infrared Nanoparticles

Abstract

Photothermal therapy (PTT) as a kind of noninvasive tumor treatment has attracted increasing research interest. However, the efficiency of existing PTT agents in the near-infrared (NIR) region is the major problem that has hindered further development of PTT. Herein, we present an effective strategy to construct the efficient photothermal agent by utilizing an intramolecular photoinduced electron transfer (PeT) mechanism, which is able to dramatically improve photothermal conversion efficiency in the NIR region. Specifically, an NIR dye (A1) constructed with dimethylamine moiety as the electron donor and the aza-BODIPY core as the electron acceptor is designed and synthesized, which can be used as a class of imaging-guided PTT agents via intramolecular PeT. After encapsulation with biodegradable polymer DSPE-mPEG, nanophotothermal agents with a small size exhibit excellent water solubility, photostability, and long-time retention in tumor. Importantly, such nanoparticles exhibit excellent photothermal conversion efficiency of ∼35.0%, and the PTT effect in vivo still remains very well even with a low dosage of 0.05 mg kg upon 808 nm NIR laser irradiation (0.5 W cm). Therefore, this reasonable design via intramolecular PeT offers guidance to construct excellent photothermal agents and subsequently may provide a novel opportunity for future clinical cancer treatment.

Achieving High‐Performance Photothermal and Photodynamic Effects upon Combining D–A Structure and Nonplanar Conformation

“…since the NIR irradiation can provide high penetration and minimal invasion. [ 14 ] In comparison to inorganic counterparts, organic nanoagents have various advantages including adjustable absorption wavelength, good biodegradability, low cost, and rapid metabolism in biological tissue [ 15 ] . Among them, conjugated polymers are dominant in this filed, [ 16,17 ] although they are relatively difficult to be synthesized and purified, resulting in difference from batch to batch and difficulty in controlling the quality.…”

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…The excellent photostability of these nano‐photosensitizers endows them with durable phototoxicity toward tumors. Moreover, reducing the fluorescence and 1 O 2 quantum yield by employing the PET process could further improve the nonradiative relaxation probability, enhancing the efficiency of photothermal conversion for PTT . Therefore, BODIPY PSs have also been used for PTT.…”

“…For instance, Xu et al constructed an NIR aza‐BODIPY (A1) functioning as two dimethylamine moieties. In this design, the dimethylamine groups were the electron donors, and the aza‐BODIPY core was the electron acceptor ( Figure ) . Compared with the control compound without dimethylamine moieties (A2), the newly designed BODIPY demonstrated a short photoluminescence lifetime (1.4 vs 4.5 ns), a low radiative quantum yield (0.003 vs 0.068), and a large nonradiative transition rate ( K nr = 7.2 × 108 s −1 vs K nr = 2.4 × 108 s −1 ) caused by PET (Figure b–e).…”

“…The relative intensities are normalized by the absorbance values at 630 nm. All panels reproduced with permission . Copyright 2018, American Chemical Society.…”

“…Typically, PSs generate heat through nonradiative relaxation pathways from excited states to the ground state by absorbing photons produced by light irradiation, eventually leading to cancer cell death . Additionally, PTT requires PSs that exhibit low fluorescence and 1 O 2 quantum yield to ensure a high nonradiative relaxation probability …”