A Novel Multi-Effect Photosensitizer for Tumor Destruction via Multimodal Imaging Guided Synergistic Cancer Phototherapy.

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Iridium(III) complexes as novel theranostic small molecules for medical diagnostics, precise imaging at a single cell level and targeted anticancer therapy.

Medical applications of iridium (III) complexes include their use as state-of-the-art theranostic agents - molecules that combine therapeutic and diagnostic functions into a single entity. These complexes offer a promising avenue in medical diagnostics, precision imaging at single-cell resolution and targeted anticancer therapy due to their unique properties. In this review we report a short summary of their application in medical diagnostics, imaging at single-cell level and targeted anticancer therapy. The exceptional photophysical properties of Iridium (III) complexes, including their brightness and photostability, make them excellent candidates for bioimaging. They can be used to image cellular processes and the microenvironment within single cells with unprecedented clarity, aiding in the understanding of disease mechanisms at the molecular level. Moreover the iridium (III) complexes can be designed to selectively target cancer cells,. Upon targeting, these complexes can act as photosensitizers for photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon light activation to induce cell death. The integration of diagnostic and therapeutic capabilities in Iridium (III) complexes offers the potential for a holistic approach to cancer treatment, enabling not only the precise eradication of cancer cells but also the real-time monitoring of treatment efficacy and disease progression. This aligns with the goals of personalized medicine, offering hope for more effective and less invasive cancer treatment strategies.

Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells.

AIM: To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects. METHODS: Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip. RESULTS: BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity. CONCLUSION: BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.

H2O2 promotes photodynamic efficacy of TMPyP4 against ovarian cancer in vitro by downregulating HIF-1α expression.

Photodynamic therapy (PDT), employing photosensitizers to induce formation of reactive oxygen species (ROS) for tumor elimination, is emerging as a promising treatment modality in oncology due to its unique benefits. However, the PDT application in ovarian cancer, the most prevalent and lethal type of gynecological malignancy with a severe hypoxic microenvironment, remains unknown. This study revealed that photosensitizer TMPyP4 exhibited enhanced efficacy under H2O2 stimulation, with minimal change in cytotoxicity compared to TMPyP4 alone. The results showed that H2O2 increased ROS production induced by TMPyP4, leading to exacerbated mitochondrial dysfunction and DNA damage, ultimately inhibiting proliferation and inducing apoptosis in ovarian cancer cells. Mechanistically, H2O2 primarily enhanced the therapeutic efficacy of PDT with TMPyP4 against ovarian cancer cells by degrading HIF-1α, which subsequently modulated the HIF-1 signaling pathway, thereby alleviating the hypoxic environment in ovarian cancer cells. Our findings underscore the therapeutic potential of targeting HIF-1α within the hypoxic microenvironment for PDT in ovarian cancer and propose a novel integrated strategy for PDT treatment of this malignancy in vitro.

Optimal methodology for percutaneous dilatational tracheostomy: a comparative analysis between conventional and multidisciplinary approaches utilizing ultrasound, flexible bronchoscopy, and microcatheter puncture in critically ill individuals of diminutive stature-a longitudinal single-institutional experience and retrospective analysis.

Background: Percutaneous dilatational tracheostomy (PDT), a bedside procedure in intensive care, enhances respiratory support for critically ill patients with benefits over traditional tracheostomy, such as improved safety, ease of use, cost-effectiveness, and operational efficiency by eliminating patient transfers to the operating room. It also minimizes complications including bleeding, infection, and inflammation. Despite decades of PDT evolution and device diversification, adaptations primarily cater to larger Western patients rather than smaller-statured Korean populations. This study assesses the efficacy and appropriateness of the Ciaglia Blue Rhino (Cook Critical Care, Bloomington, IN, USA), augmented with ultrasound, flexible bronchoscopy, and microcatheter techniques, for Korean patients with short stature. Methods: We conducted PDT on 183 intubated adults (128 male/55 female) with severe respiratory issues at a single medical center from January 2010 to December 2022. Patients were divided into two groups for retrospective analysis: a modified group (n=133) underwent PDT with ultrasound-guided flexible bronchoscopy and microcatheter puncture, and a conventional group (n=50) received PDT using only the Ciaglia Blue Rhino device. We assessed clinical and demographic characteristics, outcomes, and complications such as pneumothorax and emphysema. The study also evaluated the suitability and effectiveness of the devices for Korean patients with short stature. Results: Demographic characteristics including sex, body weight, height, body mass index, obesity status, and underlying diseases showed no significant differences between the two groups. However, the modified group was older (69.5±14.2 vs. 63.5±14.1 years; P=0.01). The sequential organ failure assessment (SOFA) and simplified acute physiology score (SAPS) II score was slightly higher in the modified groups, but no statistically significant differences were observed (7.1±2.3 vs. 6.7±2.3, P=0.31 and 46.7±9.0 vs. 44.0±9.1, P=0.08, respectively). The duration of hospital and ICU stays, as well as days post-PDT, were longer in the conventional group, yet these differences were not statistically significant (P=0.20, P=0.44, P=0.06). Total surgical time, including preparation, ultrasound, bronchoscopy, and microcatheter puncture, was significantly longer in the modified group (25.6±7.5 vs. 19.9±6.5 minutes; P<0.001), and the success rate of the first tracheal puncture was also higher (100.0% vs. 92.0%; P=0.006). Intra-operative bleeding was less frequent in the modified group (P=0.02 for tracheostomy site bleeding and P=0.002 for minor bleeding). Conclusions: PDT, performed at the bedside in intensive care settings, proves to be a swift and dependable method. Utilizing the Ciaglia Blue Rhino device, combined with ultrasound guidance, flexible bronchoscopy, and 4.0-Fr microcatheter puncture, PDT is especially effective for intubated patients who cannot be weaned from ventilation. This technique results in fewer complications than traditional tracheostomy and is particularly beneficial for patients with respiratory issues and smaller-statured Koreans, potentially reducing morbidity and mortality.

5-aminolevulinic acid photodynamic therapy inhibits the viability, invasion, and migration of cervical cancer SiHa cells by regulating the miR-152-3p/JAK1/STAT1 axis.

BACKGROUND: Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms. METHODS: Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152-3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152-3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo. RESULTS: ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152-3p. JAK1 was identified as a direct target of miR-152-3p, and ALA-PDT was found to regulate the expression levels of miR-152-3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152-3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152-3p/JAK1/STAT1 pathway expression. CONCLUSIONS: ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152-3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer.

Application of Photoactive Compounds in Cancer Theranostics: Review on Recent Trends from Photoactive Chemistry to Artificial Intelligence.

According to the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), the number of cancer cases and deaths worldwide is predicted to nearly double by 2030, reaching 21.7 million cases and 13 million fatalities. The increase in cancer mortality is due to limitations in the diagnosis and treatment options that are currently available. The close relationship between diagnostics and medicine has made it possible for cancer patients to receive precise diagnoses and individualized care. This article discusses newly developed compounds with potential for photodynamic therapy and diagnostic applications, as well as those already in use. In addition, it discusses the use of artificial intelligence in the analysis of diagnostic images obtained using, among other things, theranostic agents.

Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies.

Photodynamic therapy (PDT) is a temporally and spatially precisely controllable, noninvasive, and potentially highly efficient method of phototherapy. The three components of PDT primarily include photosensitizers, oxygen, and light. PDT employs specific wavelengths of light to active photosensitizers at the tumor site, generating reactive oxygen species that are fatal to tumor cells. Nevertheless, traditional photosensitizers have disadvantages such as poor water solubility, severe oxygen-dependency, and low targetability, and the light is difficult to penetrate the deep tumor tissue, which remains the toughest task in the application of PDT in the clinic. Here, we systematically summarize the development and the molecular mechanisms of photosensitizers, and the challenges of PDT in tumor management, highlighting the advantages of nanocarriers-based PDT against cancer. The development of third generation photosensitizers has opened up new horizons in PDT, and the cooperation between nanocarriers and PDT has attained satisfactory achievements. Finally, the clinical studies of PDT are discussed. Overall, we present an overview and our perspective of PDT in the field of tumor management, and we believe this work will provide a new insight into tumor-based PDT.

Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches.

Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.

Catalytic and selective red light-triggered photodegradation of a G-quadruplex DNA by a zinc (II) phthalocyanine.

Water-soluble phthalocyanine (Pc) derivatives have been regarded as potential G-quadruplex (G4) nucleic acid-targeting ligands for anticancer therapy and have been extensively studied as effective photosensitizers for photodynamic therapy (PDT). Understanding how photosensitizers interact with nucleic acids and the subsequent photolytic reactions is essential for deciphering the initial steps of PDT, thereby aiding in the development of new photosensitizing agents. In this study, we found that red-light irradiation of a mixture of a Zn(II) Pc derivative and an all-parallel G4 DNA leads to catalytic and selective photodegradation of the DNA by reactive oxygen species (ROS) generated from the Zn(II) Pc derivative bound to DNA through a reaction mechanism similar to that of an enzyme reaction. This finding provides a novel insight into the molecular design of a photosensitizer to enhance its PDT efficacy.

Carrier-Free Self-Assembled Nanomedicines for Promoting Apoptosis and Inhibiting Proliferation in Hepatocellular Carcinoma.

In order to improve the effectiveness of tumor treatment and reduce the toxic side effects of drugs, we formed carrier-free multifunctional nanoparticles (BI NPs) by noncovalent interaction of berberine hydrochloride and IR780. BI NPs possessed the synergistic effects of promoting apoptosis, inhibiting proliferation and metastasis of tumors, and phototherapeutic treatment. Dispersive and passive targeting ability retention (EPR) effects of BI NPs on tumor sites in vivo could be monitored by fluorescence imaging. In addition, BI NPs exhibited effective reactive oxygen species (ROS) generation and photothermal conversion capabilities, photodynamic therapy (PDT), and photothermal therapy (PTT). Importantly, BI NPs inhibit tumor suppression through the AMPK/PI3K/AKT signaling pathway to inhibit tumor proliferation and metastasis. BI NPs not only have efficient in vivo multimodal therapeutic effects but also have good biosafety and potential clinical applications.

Lipo/TK-CDN/TPP/Y6 nanoparticles inhibit cutaneous melanoma formation.

Stimulation of the innate immune stimulator of interferon genes (STING) pathway has been shown to boost anti-tumour immunity. Nevertheless, the systemic delivery of STING agonists to the tumour presents challenges. Therefore, we designed a cyclic dinucleotide (CDN)-based drug delivery system (DDS) combined photothermal therapy (PTT)/photodynamic therapy (PDT)/immunotherapy for cutaneous melanoma. We coencapsulated a reactive oxygen species (ROS)-responsive prodrug thioketone-linked CDN (TK-CDN), and photoresponsive agents chlorin E6 (Y6) within mitochondria-targeting reagent triphenylphosphonium (TPP)-modified liposomes (Lipo/TK-CDN/TPP/Y6). Lipo/TK-CDN/TPP/Y6 exhibited a photothermal effect similar to Y6, along with a superior cellular uptake rate. Upon endocytosis by B16F10 cells, Lipo/TK-CDN/TPP/Y6 generated large amounts of ROS under laser irradiation for PDT. Mice bearing B16F10 tumours were intravenously injected with Lipo/TK-CDN/TPP/Y6 and exposed to irradiation, resulting in a substantial inhibition of tumour growth. Exploration of the mechanism of anti-tumour action showed that Lipo/TK-CDN/TPP/Y6 had a stronger stimulation of STING activation and anti-tumour immune cell infiltration compared to other groups. Hence, the Lipo/TK-CDN/TPP/Y6 nanoparticles offer great potential as a DDS for targeted and on-demand drug release at tumour sites. These nanoparticles exhibit promise as a candidate for precise and controllable combination therapy in the treatment of tumours.

Upregulation of iNOS/NO in Cancer Cells That Survive a Photodynamic Challenge: Role of No in Accelerated Cell Migration and Invasion.

Anti-tumor photodynamic therapy (PDT) is a unique modality that employs a photosensitizer (PS), PS-exciting light, and O2 to generate cytotoxic oxidants. For various reasons, not all malignant cells in any given tumor will succumb to a PDT challenge. Previous studies by the authors revealed that nitric oxide (NO) from inducible NO synthase (iNOS/NOS2) plays a key role in tumor cell resistance and also stimulation of migratory/invasive aggressiveness of surviving cells. iNOS was the only NOS isoform implicated in these effects. Significantly, NO from stress-upregulated iNOS was much more important in this regard than NO from preexisting enzymes. Greater NO-dependent resistance, migration, and invasion was observed with at least three different cancer cell lines, and this was attenuated by iNOS activity inhibitors, NO scavengers, or an iNOS transcriptional inhibitor. NO diffusing from PDT-targeted cells also stimulated migration/invasion potency of non-targeted bystander cells. Unless counteracted by appropriate measures, all these effects could seriously compromise clinical PDT efficacy. Here, we will review specific examples of these negative side effects of PDT and how they might be suppressed by adjuvants such as NO scavengers or inhibitors of iNOS activity or expression.

A meta-analysis and systematic review of photodynamic therapy for diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. METHODS: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. RESULTS: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. CONCLUSION: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930.

Comparative study of photodynamic therapy (PDT) of cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. AIMS: The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). METHODS: In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. RESULT: The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. CONCLUSIONS: This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance.

Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway.

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.

Aggregation-Induced Emission CN-Based Nanoparticles to Alleviate Hypoxic Liver Fibrosis via Triggering HSC Ferroptosis and Enhancing Photodynamic Therapy.

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

The Effect of NF-κB Deactivation on Cancer Cell Response to ALA Mediated Photodynamic Therapy.

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.

Electron-Withdrawing Substituents Enhance the Type I PDT and NIR-II Fluorescence of BODIPY J Aggregates for Bioimaging and Cancer Therapy.

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.