PHOTODYNAMIC THERAPY: NEW LIGHT IN MEDICINE WORLD

Photodynamic therapy (PDT) of cancer is an alternative treatment for tumors resistant to chemo- and radiotherapy. It induces cancer cell death mainly through generation of reactive oxygen species by a laser light-activated photosensitizer. It has been suggested that the p53 tumor suppressor protein sensitizes some human cancer cells to PDT. However, there is still no direct evidence for this. We have demonstrated here for the first time that the photosensitizer protoporphyrin IX (PpIX) binds to p53 and disrupts the interaction between p53 tumor suppressor protein and its negative regulator HDM2 in vitro and in cells. Moreover, HCT116 colon cancer cells exhibited a p53-dependent sensitivity to PpIX in a dose-dependent manner, as was demonstrated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence-activated cell sorter (FACS) analysis of cell cycle profiles. We have also observed induction of p53 target pro-apoptotic genes, e.g. puma (p53-up-regulated modulator of apoptosis), and bak in PpIX-treated cells. In addition, p53-independent growth suppression by PpIX was detected in p53-negative cells. PDT treatment (2 J/cm2) of HCT116 cells induced p53-dependent activation of pro-apoptotic gene expression followed by growth suppression and induction of apoptosis.

Nanotechnology offers unique advantages over small-molecule drugs by delivering a high payload of photosensitizers to the target tissue, providing flexibility in the excitation wavelengths, enabling longer retention in the target tissue, possessing regenerative reactive oxygen speciesproducing capability and stimulating the immune system.

Photodynamic anti-cancer therapy and arachidonic acid metabolism: State of the art in 2024.

Photodynamic therapy (PDT) faces a fundamental limitation of the intrinsic energy utilization competition between fluorescence and reactive oxygen species (ROS) generation, while conventional "open-loop" protocols with pre-determined irradiation parameters risk overtreatment damage. To circumvent both challenges, we herein report phase transition nanoparticles (PTNPs) that enable self-regulated, self-reported, close-loop PDT via switching photosensitizers' molecular conformation. PTNPs were fabricated by co-encapsulating a twisted intramolecular charge transfer-aggregation-induced emission (TICT-AIE) photosensitizer (OTPA-DCPP) and the phase-change material n-docosane (C22, Tm ≈ 44.4 °C) into lipid-PEG nanoparticles. With TICT effect to reduce the singlet-triplet energy gap and AIE effect to suppress nonradiative dissipation, OTPA-DCPP exhibits polarity-enhanced type I ROS generation. C22 initially creates a rigid and polar microenvironment that stabilizes OTPA-DCPP's TICT and AIE effects, maximizing ROS generation. During PDT progress, PTNPs consumed oxygen and accumulated heat, the melted C22 above Tm created a nonpolar microenvironment, restoring the intense fluorescence while halting ROS generation. The emerged fluorescence serves as a real-time indicator of OTPA-DCPP's functional status, providing an unambiguous cue to cease irradiation to avoid energy waste and excessive heat buildup. As such, PTNPs circumvent excited-state energy reallocation challenges, which also serve as a self-reported, close-loop PDT system for safe and precise phototheranostics.

Hypoxia/pH dual-responsive nitroimidazole-modified chitosan/rose bengal derivative nanoparticles for enhanced photodynamic anticancer therapy

Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice

Cationic Fullerenes Are Effective and Selective Antimicrobial Photosensitizers

Ferroptosis promotes 5-aminolevulinate acid-based photodynamic therapy in cervical cancer.

Rheumatoid Arthritis (RA) is a crippling autoimmune disease characterized by gradual cartilage loss, bone degeneration, and persistent joint inflammation. Widespread adverse effects and ineffective drug distribution hamper the traditional treatment modalities. Recent progress in RA treatment has been advanced by nanocarrier-based phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT). These therapies work by inducing necrosis or apoptosis in inflammatory cells through the generation of reactive oxygen species via PDT or localized heat production by PTT. This also leads to a reduction in pro-inflammatory cytokines and modulates macrophage polarization (M1 to M2). This dual approach shows enhanced efficacy by targeting inflammatory cytokines while preserving healthy tissue function, providing site-specific delivery, and improving bioavailability. Preclinical investigations have demonstrated that functionalized nanocarriers for targeting macrophages and synovial fibroblasts show improved drug delivery and therapeutic outcomes. While clinical trials of PDT in refractory RA patients have shown promising results in targeting synovial hyperplasia and inflammatory markers with minimal side effects, the challenges of limited light penetration, hypoxic joint microenvironments, and poor target specificity reduce the efficacy of PDT. This review focuses on multifunctional nanoplatforms that integrate PDT and PTT therapies with nanocarriers, advanced light delivery systems, and phototherapy devices to optimise RA management. These innovations aim to enhance therapeutic precision, reduce symptoms, and improve patient adherence. It also explores cutting-edge advancements in RA treatment strategies, addresses current limitations, and proposes future research directions to bridge the gap between preclinical success and clinical application.

Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca2+ release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

Hypertrophic obstructive cardiomyopathy (HOCM) is the most common hereditary cardiovascular disease, whereas its current treatment strategies present many postoperative complications and contraindications. Photodynamic therapy (PDT) is expected to be a new strategy for HOCM due to its minimal side effects, exceptional spatiotemporal precision and low invasiveness. However, developing photosensitizer (PSs) that can be activated by long‐wavelength light with high reactive oxygen species (ROS) generation efficiency to achieve ventricular septal ablation remains a great challenge. Herein, the defect‐rich CoZnW‐layered double hydroxide (DR‐CoZnW‐LDH) is first reported as a highly active PS for NIR‐II photodynamic HOCM therapy. Hydrothermal‐synthesized CoZnW‐LDH are etched by acid treatment to obtain DR‐CoZnW‐LDH nanosheets, which exhibit superior ROS generation activity than that of the pristine CoZnW‐LDH under 1270 nm laser irradiation. Studies reveal that the thickness of the interventricular septum in HCM rats closes to normal level after treatment with bovine serum albumin‐modified DR‐CoZnW‐LDH. Echocardiographic assessments indicate that PDT intervention markedly improves left ventricular outflow tract obstruction and cardiac diastolic function in HCM rats. Furthermore, mechanism studies show that PDT‐derived ROS significantly activates Piezo2 ion channel, which promotes Piezo2‐dependent Ca2+ accumulation (increased by fourfold), leading to effective ablation of hypertrophic myocardium and reduction of left ventricular outflow tract gradient.

Tumor acidity activating multifunctional nanoplatform for NIR-mediated multiple enhanced photodynamic and photothermal tumor therapy

Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregation-induced emission (AIE) photosensitizers for photodynamic treatment of drug-resistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant CTBZPyI exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers CTBZPyI with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a MRSA-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.

The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor" structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.