Microneedle Device Delivering Aggregation-Induced Emission Photosensitizers for Enhanced Metronomic Photodynamic Therapy of Cancer

Abstract

Metronomic photodynamic therapy (mPDT), which induces cancer cell death by prolonged intermittent continuous irradiation at lower light power, has profoundly promising applications. However, the photobleaching sensitivity of the photosensitizer (PS) and the difficulty of delivery pose barriers to the clinical application of mPDT. Here, we constructed a microneedle-based device (Microneedles@AIE PSs) that combined with aggregation-induced emission (AIE) PSs to achieve enhanced mPDT for cancer. Due to the strong anti-photobleaching property of the AIE PS, it can maintain superior photosensitivity even after long-time light exposure. The delivery of the AIE PS to the tumor through a microneedle device allows for greater uniformity and depth. This Microneedles@AIE PSsbased mPDT (M-mPDT) offers better treatment outcomes and easier access, and combining M-mPDT with surgery or immunotherapy can also significantly improve the effectiveness of these clinical therapies. In conclusion, M-mPDT offers a promising strategy for the clinical application of PDT due to its better efficacy and convenience.

Optimizing cancer therapy: a review of the multifaceted effects of metronomic chemotherapy

“…They also observed the ablation of the newly formed pre-bulk tumor population through metronomic application ( Davies and Wilson, 2007 ). Other than brain tumors, the potential of mPDT has been demonstrated in various other types of cancers, such as colorectal cancer and cervical cancer ( Shi et al, 2019 ; Dai et al, 2023 ) In a study by Caverzán et al, standard and metronomic regimens of conjugated polymer nanoparticles-based PDT was assessed on glioblastoma cell lines and xenograft mouse models. They reported that mPDT regimes induced increased cancer cell death, and lowered therapeutic resistance furthermore resulted in the polarization of one of the most important cancer-related immune cell subtypes, macrophages, towards an anti-tumoral phenotype ( Caverzán et al, 2023 ).…”

“…A growing interest has been towards the construction of wireless devices that adhere to the tissue of interest and ensure the induction of PDT in a metronomic manner ( Lin et al, 2023 ). Another strategy is utilizing engineered microneedle devices for the delivery of photosensitizers in mPDT ( Dai et al, 2023 ). The nature of this treatment option calls for interdisciplinary cooperation to help it advance.…”

Advanced Light Source Technologies for Photodynamic Therapy of Skin Cancer Lesions

“…Metronomic PDT is an established technique that was initially proposed for brain tumors, where maintaining a balance between tumor cell destruction and the preservation of healthy brain tissue is essential [ 107 ]. Although it has primarily been investigated for brain tumors, it has also been explored in recent years as an alternative to conventional PDT for the treatment of skin cancer [ 101 , 108 , 109 ]. This technique involves the repeated administration of low doses of the PS, often daily or weekly, rather than a single high dose.…”

Endoplasmic Reticulum-Targeting AIE Photosensitizers to Boost Immunogenic Cell Death for Immunotherapy of Bladder Carcinoma

“…In addition, the conventional photosensitizers usually suffer from the aggregation-caused quenching (ACQ) effect, which further diminishes their ROS generation ability. The emerging aggregation-induced emission luminogens (AIEgens) represent a solution for this obstacle as the photophysical properties and ROS generation capabilities of AIEgens can be intensified in the aggregate state. ,,, …”

“…The emerging aggregation-induced emission luminogens (AIEgens) represent a solution for this obstacle as the photophysical properties and ROS generation capabilities of AIEgens can be intensified in the aggregate state. 35,36,40,41 While the exact mechanisms of PDT-induced ICD have not been fully discovered, numerous studies have demonstrated that ROS-triggered endoplasmic reticulum (ER) stress plays a pivotal role in instigating the cellular danger signaling pathways that govern ICD. 42−45 For example, hypericin, a well-known ICD inducer, can selectively induce ROS production within ER elicit an augmented immunotherapy effect against bladder carcinoma in situ, which provides a valuable reference for bladder carcinoma treatment.…”