Targeting Hypoxic Tumor Microenvironments: Biocompatible and Stable MPC-BA Micelles in Breast Cancer Treatment.

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications

Nanophotosensitive drugs for light-based cancer therapy: what does the future hold?

The promising potential of photodynamic therapy (PDT) has fueled the development of minimally invasive therapeutic approaches for cancer therapy. However, overcoming limitations in PDT efficacy in the hypoxic tumor environment and light penetration depth remains a challenge. We report the engineering of tungsten carbide nanoparticles (W2C NPs) for 1,064 nm laser-activated dual-type PDT and combined theranostics. The synthesized W2C NPs allow the robust generation of dual-type reactive oxygen species, including hydroxyl radicals (type I) and singlet oxygen (type II), using only single 1,064 nm laser activation, enabling effective PDT even in the hypoxic tumor environment. The W2C NPs also possess high photothermal performance under 1,064 nm laser irradiation, thus enabling synergistically enhanced cancer therapeutic efficacy of PDT and photothermal therapy. Additionally, the photoacoustic and X-ray computed tomography bioimaging properties of W2C NPs facilitate the integration of tumor diagnosis and therapy. The developed W2C based theranostic nanoagents increase the generation of reactive oxygen species in hypoxic tumors, improve the light penetration depth, and facilitate combined photothermal therapy and photoacoustic/computed tomography dual-mode bioimaging. These attributes could spur the exploration of transition metal carbides for advanced biomedical applications.

Multifunctional nanoplatform for tumor chemodynamic and self-amplified photodynamic cascade therapy

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Deep-penetrating photodynamic therapy with KillerRed mediated by upconversion nanoparticles.

Modulation of tumor hypoxia and redox microenvironment using nanomedicines for enhanced cancer photodynamic therapy

4 Walt dosage recommendations: how to apply them, especially for cluster devices

Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo

Photodynamic therapy (PDT) is a clinical tool for treating various tumors. PDT is achieved by a photon-induced physicochemical reaction that is induced by excitation of porphyrins by exposure to light and the subsequent generation of singlet oxygen (1O2) and other reactive oxygen species. Recently, 5-aminolevulinic acid (ALA)-based PDT has been developed as an anticancer treatment whereby ALA is orally administered as the precursor of protoporphyrin IX (PpIX) to induce the biosynthesis and accumulation of PpIX in cancer cells. Recent studies, however, provide evidence that the ABC transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of PpIX in cancer cells and thereby affects the efficacy of ALA-based PDT. In response to the photoreaction of porphyrin leading to oxidative stress, the NF-E2-related transcription factor (Nrf2) can transcriptionally upregulate many target genes, including those for metabolizing enzymes and transporters essential for cellular defense. Whereas Nrf2 upregulates transcription of the ABCG2 gene to confer cancer cells resistance, several protein kinase inhibitors reportedly interfere with the transport function of ABCG2. In fact, gefitinib inhibits ABCG2-mediated porphyrin efflux from cancer cells to enhance the efficacy of PDT in vitro. Thus, it is of great interest to develop ABCG2-specific inhibitors that are clinically applicable to photodynamic cancer therapy. Hitherto, we have performed high-speed screening, quantitative structure–activity relationship (QSAR) analysis, and in vivo validation to identify potent ABCG2-inhibitors. This chapter addresses such a new approach to improve ALA-based photodynamic cancer therapy.

Platinum supramolecular complexes based on photosensitizers have garnered great interest in photodynamic therapy (PDT) due to Pt (II) centers as chemotherapeutic agents to eliminate tumor cells completely, which greatly improve the antitumor efficacy of PDT. However, in comparison to precursor photosensitizer ligand, the formed platinum supramolecular complexes typically exhibit inferior outcomes in terms of reactive oxygen species (ROS) generation. How to boost ROS generation in the formed platinum supramolecular complexes for enhanced PDT is an enticing yet highly challenging task. Here we report a Pt-coordination-based dimeric photosensitizer complex (Cz-BTZ-Py)2Pt(OTf)2. It is found that comparing with photosensitizer ligand Cz-BTZ-Py, the formed supramolecular complex exhibit redshifts of absorption wavelength as well as enhanced ROS generation efficiency. Moreover, type-I ROS generation (O2⋅-) is produced in the formed platinum supramolecular complexes mainly due to a reduced energy gap ΔEST resulting from exciton coupling between two photosensitizer ligands. And type-I ROS (O2⋅-) generation significantly amplifies the photodynamic therapy (PDT) outcomes. In vitro evaluation shows excellent photochemotherapy performance of (Cz-BTZ-Py)2Pt(OTf)2 nanoparticles. We anticipate this work would provide a novel approach to design type-I photosensitizers for efficient PDT.

Photosensitizer in photodynamic therapy (PDT) accumulates in both tumor and adjacent normal tissue due to low selective biodistribution, results in undesirable side effect with limited clinic application. Herein, an intelligent nanoplatform is reported that selectively acts as reactive oxygen species (ROS) scavenger in normal tissue but as ROS generator in tumor microenvironment (TME) to differentially control ROS level in tumor and surrounding normal tissue during PDT. By down-regulating the produced ROS with dampened cytokine wave in normal tissue after PDT, the nanoplatform reduces the inflammatory response of normal tissue in PDT, minimizing the side effect and tumor metastasis in PDT. Alternatively, the nanoplatform switches from ROS scavenger to generator through the glutathione (GSH) responsive degradation in TME, which effectively improves the PDT efficacy with reduced GSH level and amplified oxidative stress in tumor. Simultaneously, the released Mn ions provide real-time and in situ signal change of magnetic resonance imaging (MRI) to monitor the reversal process of catalysis activity and achieve accurate tumor diagnosis. This TME-responsive ROS scavenger/generator with activable MRI contrast may provide a new dimension for design of next-generation PDT agents with precise diagnosis, high therapeutic efficacy, and low side effect.

The normal microbial occupants of the mammalian intestine are crucial for maintaining gut homeostasis, yet the mechanisms by which intestinal cells perceive and respond to the microbiota are largely unknown. Intestinal epithelial contact with commensal bacteria and/or their products has been shown to activate noninflammatory signaling pathways, such as extracellular signal-related kinase (ERK), thus influencing homeostatic processes. We previously demonstrated that commensal bacteria stimulate ERK pathway activity via interaction with formyl peptide receptors (FPRs). In the current study, we expand on these findings and show that commensal bacteria initiate ERK signaling through rapid FPR-dependent reactive oxygen species (ROS) generation and subsequent modulation of MAP kinase phosphatase redox status. ROS generation induced by the commensal bacteria Lactobacillus rhamnosus GG and the FPR peptide ligand, N-formyl-Met-Leu-Phe, was abolished in the presence of selective inhibitors for G protein-coupled signaling and FPR ligand interaction. In addition, pretreatment of cells with inhibitors of ROS generation attenuated commensal bacteria-induced ERK signaling, indicating that ROS generation is required for ERK pathway activation. Bacterial colonization also led to oxidative inactivation of the redox-sensitive and ERK-specific phosphatase, DUSP3/VHR, and consequent stimulation of ERK pathway signaling. Together, these data demonstrate that commensal bacteria and their products activate ROS signaling in an FPR-dependent manner and define a mechanism by which cellular ROS influences the ERK pathway through a redox-sensitive regulatory circuit.

Photodynamic therapy (PDT) represents a targeted approach for cancer treatment that employs light and photosensitizers (PSs) to induce the generation of reactive oxygen species (ROS). However, PDT faces obstacles including insufficient PS localization, limited light penetration, and treatment resistance. A potential solution lies in nanogenerators (NGs), which function as self-powered systems capable of generating electrical energy. Recent progress in piezoelectric and triboelectric NGs showcases promising applications in cancer research and drug delivery. Integration of NGs with PDT holds the promise of enhancing treatment efficacy by ensuring sustained PS illumination, enabling direct electrical control of cancer cells, and facilitating improved drug administration. This comprehensive review aims to augment our comprehension of PDT principles, explore associated challenges, and underscore the transformative capacity of NGs in conjunction with PDT. By harnessing NG technology alongside PDT, significant advancement in cancer treatment can be realized. Herein, we present the principal findings and conclusions of this study, offering valuable insights into the integration of NGs to overcome barriers in PDT.