Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

Abstract

Photodynamic therapy (PDT) has emerged as a promising locoregional therapy of hepatocellular carcinoma (HCC). The utilization of luminogens with aggregation-induced emission (AIE) characteristics provides a new opportunity to design functional photosensitizers (PS). PSs targeting the critical organelles that are susceptible to reactive oxygen species damage is a promising strategy to enhance the effectiveness of PDT. In this paper, a new PS, 1-[2-hydroxyethyl]-4-[4-(1,2,2-triphenylvinyl)styryl]pyridinium bromide (TPE-Py-OH) of tetraphenylethylene derivative with AIE feature was designed and synthesized for PDT. The TPE-Py-OH can not only simultaneously target lipid droplets and mitochondria, but also stay in cells for a long period (more than 7 days). Taking advantage of the long retention ability of TPE-Py-OH in tumor, the PDT effect of TPE-Py-OH can be activated through multiple irradiations after one injection, which provides a specific multiple light-activated PDT effect. We believe that this AIE-active PS will be promising for the tracking and photodynamic ablation of HCC with sustained effectiveness.

Photodynamic Priming Overcomes Per‐ and Polyfluoroalkyl Substance (PFAS)‐Induced Platinum Resistance in Ovarian Cancer†

“…The JC-1 readout was also not affected by incubation with the photosensitizer alone or irradiation without the photosensitizer (Figure S15). While it is known that the JC-1 probe is easily photobleached, the lack of effect after irradiation may be due to the low light doses used, since irradiation time ranged from 1-21 s. Other studies evaluating PDT have also used the JC-1 probe to estimate DΨ m and, consistent with the present study, JC-1 dye was administered after irradiation (79,(87)(88)(89)(90). It is worth noting that administration of JC-1 dye prior to PDT has been reported (78).…”

“…PFAS are ubiquitous environmental contaminants that are known to adversely affect various bodily systems, including the female reproductive system (2,5–9,45,46,10). PFAS have been associated with adverse health effects in uterine and ovarian tissue, as well as increased risk of reproductive disorders such as PCOS and even cancer (5–7,9,11,47–49). Our recent study (12) linked exposure to select PFAS with platinum resistance in ovarian cancer.…”

Aggregation‐induced emission luminogens for in vivo molecular imaging and theranostics in cancer

“…With the same TPE core, TPE–Py–OH was another TPE derivative PS with AIE features. [ 141 ] It was designed to target LD and mitochondria and had long‐term intracellular retention over one week. After multiple irradiations, the TPE–Py–OH could significantly ablate the tumors with sustained PDT effect for hepatocellular carcinoma in mice models.…”

Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application

“…In addition to the important role of mitochondria in cellular metabolism, lipid droplets (LDs) also play corresponding roles in biological activities as lipid storage organelles. Li et al 75 designed a TPE-based AIE PS (TPE-Py-OH) targeting both mitochondria and LDs for PDT of hepatocellular carcinoma (Fig. 7).…”