Surfactant-Free Green Synthesis of Au@Chlorophyll Nanorods for NIR PDT-Elicited CDT in Bladder Cancer Therapy

Abstract

The facile and straightforward fabrication of NIR-responsive theranostic materials with high biocompatibility is still an unmet need for nanomedicine applications. Here, we used a natural photosensitizer, iron chlorophyll (Chl/Fe), for the J-aggregate template-assisted synthesis of Au@Chl/Fe nanorods with high stability. The assembly of a high amount of Chl/Fe J-aggregate onto the Au surface enabled red–NIR fluorescence for monitoring and tracking residential tumor lesions. The Chl/Fe moieties condensed on the nanorods could change the redox balance by the photon induction of reactive oxygen species and attenuate iron-mediated lipid peroxidation by inducing a Fenton-like reaction. After conjugation with carboxyphenylboronic acid (CPBA) to target the glycoprotein receptor on T24 bladder cancer (BC) cells, the enhanced delivery of Au@Chl/Fe-CPBA nanorods could induce over 85% cell death at extremely low concentrations of 0.16 ppm[Au] at 660 nm and 1.6 ppm[Au] at 785 nm. High lipid peroxidation, as shown by BODIPY staining and GSH depletion, was observed when treated T24 cells were exposed to laser irradiation, suggesting that preliminary photodynamic therapy (PDT) can revitalize Fenton-like reaction-mediated chemodynamic ferroptosis in T24 cells. We also manipulated the localized administration of Au@Chl-Fe combined with PDT at restricted regions in orthotopic tumor-bearing mice to cure malignant BC successfully without recurrence. By intravesical instillation of the Au@Chl/Fe-CPBA nanorods, this localized treatment could prevent the material from entering the systemic circulation, thus minimizing systemic toxicity. Upon activating NIR-PDT-elicited chemodynamic therapy, ultrasound imaging revealed almost complete tumor remission. Anti-tumor efficacy and survival benefit were achieved with a green photosensitizer.

Recent Progress in Nanomaterial-Based Biosensors and Theranostic Nanomedicine for Bladder Cancer

“…Facing the clinical challenge of CDT, scientists prefer utilizing CDT combined with other therapies, such as PTT or PDT, to apply to bladder cancer. Liao et al presented a CDT-based approach combined with photodynamic therapy (PDT) in which PDT excites CDT in the NIR region to treat bladder cancer (Figure 14a) [129]. The photosensitizer Au@Chl/Fe-CPBA (Chl/Fe for iron chlorophyll and carboxyphenylboronic for CPBA) reduces toxicity and avoids it from entering into systemic circulation by an intravesical instillation [129] belonging to the iron-based inorganic material.…”

“…Liao et al presented a CDT-based approach combined with photodynamic therapy (PDT) in which PDT excites CDT in the NIR region to treat bladder cancer (Figure 14a) [129]. The photosensitizer Au@Chl/Fe-CPBA (Chl/Fe for iron chlorophyll and carboxyphenylboronic for CPBA) reduces toxicity and avoids it from entering into systemic circulation by an intravesical instillation [129] belonging to the iron-based inorganic material. As demonstrated in Figure 14a, the experiment illustrates that the direct NIR light-induced PDT, before a lengthy CDT period, accelerates the conversion by ferrous ions in the tumor microenvironment from H 2 O 2 to O 2 and •OH, which exacerbates the inhibition of the growth of bladder cancer cells, resulting in the immediate consumption of the glutathione (GSH) antioxidant molecules and the triggering of membrane lipid peroxidation [129].…”

“…The photosensitizer Au@Chl/Fe-CPBA (Chl/Fe for iron chlorophyll and carboxyphenylboronic for CPBA) reduces toxicity and avoids it from entering into systemic circulation by an intravesical instillation [129] belonging to the iron-based inorganic material. As demonstrated in Figure 14a, the experiment illustrates that the direct NIR light-induced PDT, before a lengthy CDT period, accelerates the conversion by ferrous ions in the tumor microenvironment from H 2 O 2 to O 2 and •OH, which exacerbates the inhibition of the growth of bladder cancer cells, resulting in the immediate consumption of the glutathione (GSH) antioxidant molecules and the triggering of membrane lipid peroxidation [129]. Localized therapy with the nanophotosensitizer provided the advantage of boosting distribution at the bladder wall and reducing systemic toxicity by preventing it from entering the systemic circulation, attributed to its delivery through intravesical instillation.…”

Ferroptosis: A new therapeutic target for bladder cancer

“…A variety of nano drugs have been reported to specifically adhere to bladder cancer cells and deliver iron through endocytosis when exposed to laser irradiation, resulting in ROS generation and accumulation and subsequent GSH and GPX4 depletion, ultimately leading to ferroptosis ( Liao et al, 2022 ). Another approach is to enhance photodynamic therapy (PDT)-chemodynamic therapy (CDT) sensitivity and induce toxicity ( Chin et al, 2022 ; Liao et al, 2022 ). AuNRs&IONs@Gel is a gel delivery platform with embedded gold nanorods (AuNRs) and iron oxide nanoparticles (IONs).…”

Synergistic ferroptosis‐starvation therapy for bladder cancer based on hyaluronic acid modified metal–organic frameworks

“…Conversely, nanomaterials with passive and active target abilities can enhance accumulation at the tumor site and reduce adverse effects 14 . For example, Liao et al reported a nanodrug that specifically targets BCa cells to deliver iron ions, produce excess ROS, and ultimately lead to ferroptosis 15 . Moreover, AuNRs, IONs@Gel, 16 and gold clusters (PAA4 and PAA5) 17 have also been reported have potential for BCa treatment targeting the ferroptosis pathway.…”