Photodynamic Therapy Of Cancer Research Articles

Quantitative Changes in Pro-Oncogenic and Tumor-Suppressing MicroRNA in the Regional Lymph Node during Photodynamic Therapy of Experimental Breast Cancer.

We studied quantitative changes in microRNAs in the axillary lymph node (regional lymph node of the mammary gland) and in the breast tumor tissue. The quantity of pro-oncogenic microRNAs (miR-21 and miR-221) in the regional lymph node decreased in the group after photodynamic therapy of the breast cancer. At the same time, the quantity of pro-oncogenic miR-27a remained decreased in this group, as well as in the group with breast cancer without treatment. The quantity of tumor-suppressing miR-429 in the regional lymph node after photodynamic therapy of breast cancer remained at the same level with the quantity in the group of rats with breast cancer without treatment.

Bibliometric and visual analysis of photodynamic therapy for lung cancer from 2010 to 2022.

A growing body of research shows that photodynamic therapy (PDT) has become an important mode of treatment in the field of lung cancer (LC) in recent years. Although numerous papers related to PDT in LC have been published, no bibliometric studies have been conducted to summarize the research prospects and highlight the research trends and hotspots in this field. This bibliometric analysis was conducted to investigate and provide a systematic understanding of the development of PDT research for LC over the past 13 years with the aim of providing a reference for new directions and strategies in the field of PDT for LC. In May 2023, relevant publications from the Web of Science Core Collection were downloaded, and CiteSpace and VOSviewer were used to conduct the scientometrics analysis in this study.Results: A total of 2,932 articles and reviews that met the inclusion criteria were retrieved, with China dominated the volume of publications from 2010 to 2022 and the most prolific institution was Shanghai Jiao Tong University. PDT can be utilized for the diagnosis and treat LC. Bronchoscopic fluorescence diagnosis using photosensitizers helps to detect tumor changes in the large bronchial mucosa. In the future, we should actively explore the use of new photosensitizers, including the development of nanomaterials, in addition, PDT combined with other treatments can significantly prolong survival. This combination therapy may also be the direction of future research.

Combined Photosensitive Gene Therapy Effective Against Triple-Negative Breast Cancer in Mice Model.

Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges. The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs. Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy. Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC.

PH-responsive upconversion mesoporous silica nanospheres for combined multimodal diagnostic imaging and targeted photodynamic and photothermal cancer therapy

pH-responsive upconversion mesoporous silica nanospheres for combined multimodal diagnostic imaging and targeted photodynamic and photothermal cancer therapy

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

Hypoxia-triggered degradable porphyrinic covalent organic framework for synergetic photodynamic and photothermal therapy of cancer

Nanomedicines receive great attention in cancer treatment. Nevertheless, nonbiodegradable and long-term retention still limit their clinical translation. Herein, we successfully synthesize a hypoxia-triggered degradable porphyrinic covalent organic framework (HPCOF) for antitumor therapy in vivo. HPCOF possesses wide absorption in near infrared region (NIR) which endows HPCOF excellent photothermal conversion efficiency and photoacoustic (PA) imaging ability. Moreover, HPCOF exhibits excellent photodynamic and photothermal effect under special-wavelength laser irradiation. For the first time, the in vitro and in vivo tests demonstrate that HPCOF shows effective therapeutic effect for the combination of PDT and PTT under the monitoring of PA imaging. Importantly, in tumor region, HPCOF could be triggered by hypoxia microenvironment and collapsed gradually, then cleared from the body after treatment. This work fabricates a novel COF for cancer treatment and testifies great potential of HPCOF in clinical application with reducing long-term toxicity.

Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.

FAP Targeting of Photosensitizer-Loaded Polymersomes for Increased Light-Activated Cell Killing.

As current chemo- and photodynamic cancer therapies are associated with severe side effects due to a lack of specificity and to systemic toxicity, innovative solutions in terms of targeting and controlled functionality are in high demand. Here, we present the development of a polymersome nanocarrier equipped with targeting molecules and loaded with photosensitizers for efficient uptake and light-activated cell killing. Polymersomes were self-assembled in the presence of photosensitizers from a mixture of nonfunctionalized and functionalized PDMS-b-PMOXA diblock copolymers, the latter designed for coupling with targeting ligands. By encapsulation inside the polymersomes, the photosensitizer Rose Bengal was protected, and its uptake into cells was mediated by the nanocarrier. Inhibitor of fibroblast activation protein α (FAPi), a ligand for FAP, was attached to the polymersomes' surface and improved their uptake in MCF-7 breast cancer cells expressing relatively high levels of FAP on their surface. Once internalized by MCF-7, irradiation of Rose Bengal-loaded FAPi-polymersomes generated reactive oxygen species at levels high enough to induce cell death. By combining photosensitizer encapsulation and specific targeting, polymersomes represent ideal candidates as therapeutic nanocarriers in cancer treatment.

An ER-targeted, Viscosity-sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway.

The concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER-ZS for endoplasmic reticulum (ER)-targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER-targeted functional groups (p-toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER-ZS demonstrated substantial fluorescence turn-on only after binding to the ER, independent of other physiological environments. In addition, ER-ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER-ZS is a type I photosensitizer, producing O2 ⋅- and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2 ) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

An ER‐targeted, Viscosity‐sensitive Hemicyanine Dye for the Diagnosis of Nonalcoholic Fatty Liver and Photodynamic Cancer Therapy by Activating Pyroptosis Pathway

AbstractThe concept of molecular design, integrating diagnostic and therapeutic functions, aligns with the general trend of modern medical advancement. Herein, we rationally designed the smart molecule ER‐ZS for endoplasmic reticulum (ER)‐targeted diagnosis and treatment in cell and animal models by combining hemicyanine dyes with ER‐targeted functional groups (p‐toluenesulfonamide). Owing to its ability to target the ER with a highly specific response to viscosity, ER‐ZS demonstrated substantial fluorescence turn‐on only after binding to the ER, independent of other physiological environments. In addition, ER‐ZS, being a small molecule, allows for the diagnosis of nonalcoholic fatty liver disease (NAFLD) via liver imaging based on high ER stress. Importantly, ER‐ZS is a type I photosensitizer, producing O2⋅− and ⋅OH under light irradiation. Thus, after irradiating for a certain period, the photodynamic therapy inflicted severe oxidative damage to the ER of tumor cells in hypoxic (2 % O2) conditions and activated the unique pyroptosis pathway, demonstrating excellent antitumor capacity in xenograft tumor models. Hence, the proposed strategy will likely shed new light on integrating molecular optics for NAFLD diagnosis and cancer therapy.

Hybrid heterogeneous phantoms for biomedical applications: a demonstration to dosimetry validation.

Phantoms simultaneously mimicking anatomical and optical properties of real tissues can play a pivotal role for improving dosimetry algorithms. The aim of the paper is to design and develop a hybrid phantom model that builds up on the strengths of solid and liquid phantoms for mimicking various anatomical structures for prostate cancer photodynamic therapy (PDT) dosimetry validation. The model comprises of a photosensitizer-embedded gelatin lesion within a liquid Intralipid prostate shape that is surrounded by a solid silicone outer shell. The hybrid phantom was well characterized for optical properties. The final assembled phantom was also evaluated for fluorescence tomographic reconstruction in conjunction with SpectraCure's IDOSE software. The developed model can lead to advancements in dosimetric evaluations. This would improve PDT outlook as a clinical treatment modality and boost phantom based standardization of biophotonic devices globally.

Zinc phthalocyanine loaded- antibody functionalized nanoparticles enhance photodynamic therapy in monolayer (2-D) and multicellular tumour spheroid (3-D) cell cultures.

In conventional photodynamic therapy (PDT), effective delivery of photosensitizers (PS) to cancer cells can be challenging, prompting the exploration of active targeting as a promising strategy to enhance PS delivery. Typically, two-dimensional (2-D) monolayer cell culture models are used for investigating targeted photodynamic therapy. However, despite their ease of use, these cell culture models come with certain limitations due to their structural simplicity when compared to three-dimensional (3-D) cell culture models such as multicellular tumour spheroids (MCTSs). In this study, we prepared gold nanoparticles (AuNPs) that were functionalized with antibodies and loaded with tetra sulphonated zinc phthalocyanine (ZnPcS4). Characterization techniques including transmission electron microscopy (TEM) was used to determine the size and morphology of the prepared nanoconjugates. We also conducted a comparative investigation to assess the photodynamic effects of ZnPcS4 alone and/or conjugated onto the bioactively functionalized nanodelivery system in colorectal Caco-2 cells cultured in both in vitro 2-D monolayers and 3-D MCTSs. TEM micrographs revealed small, well distributed, and spherical shaped nanoparticles. Our results demonstrated that biofunctionalized nanoparticle mediated PDT significantly inhibited cell proliferation and induced apoptosis in Caco-2 cancer monolayers and, to a lesser extent, in Caco-2 MCTSs. Live/dead assays further elucidated the impact of actively targeted nanoparticle-photosensitizer nanoconstruct, revealing enhanced cytotoxicity in 2-D cultures, with a notable increase in dead cells post-PDT. In 3-D spheroids, however, while the presence of targeted nanoparticle-photosensitizer system facilitated improved therapeutic outcomes, the live/dead results showed a higher number of viable cells after PDT treatment compared to their 2-D monolayer counterparts suggesting that MCTSs showed more resistance to PS drug as compared to 2-D monolayers. These findings suggest a high therapeutic potential of the multifunctional nanoparticle as a targeted photosensitizer delivery system in PDT of colorectal cancer. Furthermore, the choice of cell culture model influenced the response of cancer cells to PDT treatment, highlighting the feasibility of using MCTSs for targeted PS delivery to colorectal cancer cells.

Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy.

Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2•- generation are conjugated with integrin αvβ3 binding cRGD to achieve targeted photodynamic therapy.

Innovative approaches for cancer treatment: graphene quantum dots for photodynamic and photothermal therapies.

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.

Perphenazine modified pillar[5]arene based nano-assemblies for synergistic photothermal and photodynamic cancer therapy.

Nano-assemblies based on perphenazine modified pillar[5]arene were constructed successfully for synergistic photothermal and photodynamic (I&II) cancer therapy.

A comprehensive review on singlet oxygen generation in nanomaterials and conjugated polymers for photodynamic therapy in the treatment of cancer.

A key role in lessening humanity's continuous fight against cancer could be played by photodynamic therapy (PDT), a minimally invasive treatment employed in the medical care of a range of benign disorders and malignancies. Cancerous tissue can be effectively removed by using a light source-excited photosensitizer. Singlet oxygen and reactive oxygen species are produced via the photosensitizer as a result of this excitation. In the recent past, researchers have put in tremendous efforts towards developing photosensitizer molecules for photodynamic treatment (PDT) to treat cancer. Conjugated polymers, characterized by their efficient fluorescence, exceptional photostability, and strong light absorption, are currently under scrutiny for their potential applications in cancer detection and treatment through photodynamic and photothermal therapy. Researchers are exploring the versatility of these polymers, utilizing sophisticated chemical synthesis and adaptable polymer structures to create new variants with enhanced capabilities for generating singlet oxygen in photodynamic treatment (PDT). The incorporation of photosensitizers into conjugated polymer nanoparticles has proved to be beneficial, as it improves singlet oxygen formation through effective energy transfer. The evolution of nanotechnology has emerged as an alternative avenue for enhancing the performance of current photosensitizers and overcoming significant challenges in cancer PDT. Various materials, including biocompatible metals, polymers, carbon, silicon, and semiconductor-based nanomaterials, have undergone thorough investigation as potential photosensitizers for cancer PDT. This paper outlines the recent advances in singlet oxygen generation by investigators using an array of materials, including graphene quantum dots (GQDs), gold nanoparticles (Au NPs), silver nanoparticles (Ag NPs), titanium dioxide (TiO2), ytterbium (Yb) and thulium (Tm) co-doped upconversion nanoparticle cores (Yb/Tm-co-doped UCNP cores), bismuth oxychloride nanoplates and nanosheets (BiOCl nanoplates and nanosheets), and others. It also stresses the synthesis and application of systems such as amphiphilic block copolymer functionalized with folic acid (FA), polyethylene glycol (PEG), poly(β-benzyl-L-aspartate) (PBLA10) (FA-PEG-PBLA10) functionalized with folic acid, tetra(4-hydroxyphenyl)porphyrin (THPP-(PNIPAM-b-PMAGA)4), pyrazoline-fused axial silicon phthalocyanine (HY-SiPc), phthalocyanines (HY-ZnPcp, HY-ZnPcnp, and HY-SiPc), silver nanoparticles coated with polyaniline (Ag@PANI), doxorubicin (DOX) and infrared (IR)-responsive poly(2-ethyl-2-oxazoline) (PEtOx) (DOX/PEtOx-IR NPs), particularly in NIR imaging-guided photodynamic therapy (fluorescent and photoacoustic). The study puts forward a comprehensive summary and a convincing justification for the usage of the above-mentioned materials in cancer PDT.

Clinical Practice of Photodynamic Therapy for Non-Small Cell Lung Cancer in Different Scenarios: Who Is the Better Candidate?

Photodynamic therapy (PDT) is a relatively safe and highly selectivity antitumor treatment, which might be increasingly used as a supplement to conventional therapies. A clinical overview and detailed comparison of how to select patients and lesions for PDT in different scenarios are urgently needed to provide a basis for clinical treatment. This review demonstrates the highlights and obstacles of applying PDT for lung cancer and underlines points worth considering when planning to initiate PDT. The aim was to make out the appropriate selection and help PDT develop efficacy and precision through a better understanding of its clinical use. Increasing evidence supports the feasibility and safety of PDT in the treatment of non-small cell lung cancer. It is important to recognize the factors that influence the efficacy of PDT to develop individualized management strategies and implement well-designed procedures. These important issues should be worth considering in the present and further research.

Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer.

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Advancing rhodium nanoparticle-based photodynamic cancer therapy: quantitative proteomics and in vivo assessment reveal mechanisms targeting tumor metabolism, progression and drug resistance.

Rhodium nanoparticles have been recently discovered as good photosensitizers with great potential in cancer photodynamic therapy by effectively inducing cytotoxicity in cancer cells under near-infrared laser. This study evaluates the molecular mechanisms underlying such antitumoral effect through quantitative proteomics. The results revealed that rhodium nanoparticle-based photodynamic therapy disrupts tumor metabolism by downregulating key proteins involved in ATP synthesis and mitochondrial function, leading to compromised energy production. The treatment also induces oxidative stress and apoptosis while targeting the invasion capacity of cancer cells. Additionally, key proteins involved in drug resistance are also affected, demonstrating the efficacy of the treatment in a multi-drug resistant cell line. In vivo evaluation using a chicken embryo model also confirmed the effectiveness of the proposed therapy in reducing tumor growth without affecting embryo viability.

A highly fluorescent and readily accessible all-organic photosensitizer model for advancing image-guided cancer PDT.

The potential of using image-guided photodynamic therapy (ig-PDT) for cancer, especially with highly biocompatible fluorescent agents free of heavy atoms, is well recognized. This is due to key advantages related to minimizing adverse side effects associated with standard cancer chemotherapy. However, this theragnostic approach is strongly limited by the lack of synthetically-accessible and easily-modulable chemical scaffolds, enabling the rapid design and construction of advanced agents for clinical ig-PDT. In fact, there are still very few ig-PDT agents clinically approved. Herein we report a readily accessible, easy-tunable and highly fluorescent all-organic small photosensitizer, as a model design for accelerating the development and translation of advanced ig-PDT agents for cancer. This scaffold is based on BODIPY, which assures high fluorescence, accessibility, and ease of performance adaptation by workable chemistry. The optimal PDT performance of this BODIPY dye, tested in highly resistant pancreatic cancer cells, despite its high fluorescent behavior, maintained even after fixation and cancer cell death, is based on its selective accumulation in mitochondria. This induces apoptosis upon illumination, as evidenced by proteomic studies and flow cytometry. All these characteristics make the reported BODIPY-based fluorescent photosensitizer a valuable model for the rapid development of ig-PDT agents for clinical use.