Recent advances in strategies for overcoming hypoxia in photodynamic therapy of cancer.

Photodynamic Therapy for Urological Malignancies: Past to Current Approaches

Oxygen Nanoshuttles for Tumor Oxygenation and Enhanced Cancer Treatment

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.

Owing to their unique photophysical and physicochemical properties, nanoscale photosensitizers (nano-PSs) comprising nanocarriers and molecular photosensitizers (PSs) have emerged as the practical solutions to circumvent current limitations in photodynamic therapy (PDT) of cancer. Nanosized materials have demonstrated their superiority either as the delivery vehicles for PSs to enhance the therapeutic efficacy in selective PDT or as the active participants to improve the energy conversion under a near-infrared light for deep tumour treatment. In this mini-review, we provide an overview of recent progress on nano-PSs for advanced PDT by elaborating three key elements in the photodynamic reaction, i.e. PS, oxygen, and light. Specifically, we discuss the state-of-the-art design of nano-PSs via the following strategies: (a) intracellular PS delivery based on hierarchical modifications, (b) stimuli-responsive nano-PSs targeting the tumour microenvironment, and (c) improved photophysical characteristics of nano-PSs as the energy transducers under deep tissue-penetrating light irradiation. In addition, the utilities of nano-PSs for combinatory therapy or for theragnostic purposes were also discussed. In the end, the current challenges and future perspectives of nano-PSs towards clinical translation were also highlighted along with the concluding remarks.

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm2, fluence rate: 75 mW/cm2) and (ii) low light fluence and fluence rate (128 J/cm2 and 14 mW/cm2 and 128 J/cm2 and 7 mW/cm2) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time.

Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate

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

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.

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.

Photodynamic Therapy for Early Stage Central Type of Lung Cancer

Core-shell structured nanoparticles for photodynamic therapy-based cancer treatment and related imaging

Overcoming photodynamic resistance and tumor targeting dual-therapy mediated by indocyanine green conjugated gold nanospheres

Graphene quantum dots (GQDs) hold great promise for photodynamic and photothermal cancer therapies. Their unique properties, such as exceptional photoluminescence, photothermal conversion efficiency, and surface functionalization capabilities, make them attractive candidates for targeted cancer treatment. GQDs have a high photothermal conversion efficiency, meaning they can efficiently convert light energy into heat, leading to localized hyperthermia in tumors. By targeting the tumor site with laser irradiation, GQD-based nanosystems can induce selective cancer cell destruction while sparing healthy tissues. In photodynamic therapy, light-sensitive compounds known as photosensitizers are activated by light of specific wavelengths, generating reactive oxygen species that induce cancer cell death. GQD-based nanosystems can act as excellent photosensitizers due to their ability to absorb light across a broad spectrum; their nanoscale size allows for deeper tissue penetration, enhancing the therapeutic effect. The combination of photothermal and photodynamic therapies using GQDs holds immense potential in cancer treatment. By integrating GQDs into this combination therapy approach, researchers aim to achieve enhanced therapeutic efficacy through synergistic effects. However, biodistribution and biodegradation of GQDs within the body present a significant hurdle to overcome, as ensuring their effective delivery to the tumor site and stability during treatment is crucial for therapeutic efficacy. In addition, achieving precise targeting specificity of GQDs to cancer cells is a challenging task that requires further exploration. Moreover, improving the photothermal conversion efficiency of GQDs, controlling reactive oxygen species generation for photodynamic therapy, and evaluating their long-term biocompatibility are all areas that demand attention. Scalability and cost-effectiveness of GQD synthesis methods, as well as obtaining regulatory approval for clinical applications, are also hurdles that need to be addressed. Further exploration of GQDs in photothermal and photodynamic cancer therapies holds promise for advancements in targeted drug delivery, personalized medicine approaches, and the development of innovative combination therapies. The purpose of this review is to critically examine the current trends and advancements in the application of GQDs in photothermal and photodynamic cancer therapies, highlighting their potential benefits, advantages, and future perspectives as well as addressing the crucial challenges that need to be overcome for their practical application in targeted cancer therapy.

A multifunctional nanosystem catalyzed by cascading natural glucose oxidase and Fe3O4 nanozymes for synergistic chemodynamic and photodynamic cancer therapy

Photodynamic therapy for lung cancers based on novel photodynamic diagnosis using talaporfin sodium (NPe6) and autofluorescence bronchoscopy