Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

Conjugate of Natural Bacteriochlorin with Doxorubicin for Combined Photodynamic and Chemotherapy.

Chemotherapy is among the main classical approaches to the treatment of oncologic diseases. Its efficiency has been comprehensively proven by clinical examinations; however, the low selectivity of chemotherapeutic agents limits the possibilities of this method, making it necessary to search for new approaches to the therapy of oncologic diseases. Photodynamic therapy is the least invasive method and a very efficient alternative for the treatment of malignant tumors; however, its efficiency depends on the depth of light penetration into the tissue and on the degree of oxygenation of the treatment zone. In this work, a hitherto unknown conjugate of a natural bacteriochlorin derivative and doxorubicin was obtained. In vitro and in vivo studies showed a more pronounced activity of the conjugate against MCF-7 and 4T1 cells and its higher tumorotropicity in animal tumor-bearing animals compared to free anthracycline antibiotic. The suggested conjugate implements the advantages of photodynamic therapy and chemotherapy and has great potential in cancer treatment.

Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL)-A Scoping Review Based on Preclinical Studies.

Purpose: Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) stabilizes the corneal stroma and eliminates microorganisms. Numerous PACK-CXL protocols, using different energy sources and chromophores, have been applied in preclinical studies, including live animal studies, with various experimental designs and endpoints. So far, a systematic mapping of the applied protocols and consistency across studies seems lacking but is essential to guide future research. Methods: The scoping review protocol was in line with the JBI Manual for Evidence Synthesis. Electronic databases were searched (Embase, MEDLINE, Scopus, Web of Science) to identify eligible records, followed by a two-step selection process (title and abstract screening, full text screening) for record inclusion. We extracted information on (1) different PACK-CXL protocol characteristics; (2) infectious pathogens tested; (3) study designs and experimental settings; and (4) endpoints used to determine antimicrobial and tissue stabilizing effects. The information was charted in frequency maps. Results: The searches yielded 3654 unique records, 233 of which met the inclusion criteria. With 103 heterogeneous endpoints, the researchers investigated a wide range of PACK-CXL protocols. The tested microorganisms reflected pathogens commonly associated with infectious keratitis. Bacterial solutions and infectious keratitis rabbit models were the most widely used models to study the antimicrobial effects of PACK-CXL. Conclusions: If preclinical PACK-CXL studies are to guide future translational research, further cross-disciplinary efforts are needed to establish, promote, and facilitate acceptance of common endpoints relevant to PACK-CXL. Translational Relevance: Systematic mapping of PACK-CXL protocols in preclinical studies guides future translational research.

Acidity-activatable dynamic hybrid nanoplatforms derived from extracellular vesicles of M1 macrophages enhance cancer immunotherapy through synergistic triple immunotherapy.

Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Fe-loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence.

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.

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Adjunctive antimicrobial photodynamic therapy for treating periodontal and peri-implant diseases.

BACKGROUND: Periodontitis and peri-implant diseases are chronic inflammatory conditions occurring in the mouth. Left untreated, periodontitis progressively destroys the tooth-supporting apparatus. Peri-implant diseases occur in tissues around dental implants and are characterised by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone. Treatment aims to clean the pockets around teeth or dental implants and prevent damage to surrounding soft tissue and bone, including improvement of oral hygiene, risk factor control (e.g. encouraging cessation of smoking) and surgical interventions. The key aspect of standard non-surgical treatment is the removal of the subgingival biofilm using subgingival instrumentation (SI) (also called scaling and root planing). Antimicrobial photodynamic therapy (aPDT) can be used an adjunctive treatment to SI. It uses light energy to kill micro-organisms that have been treated with a light-absorbing photosensitising agent immediately prior to aPDT. OBJECTIVES: To assess the effects of SI with adjunctive aPDT versus SI alone or with placebo aPDT for periodontitis and peri-implant diseases in adults. SEARCH METHODS: We searched the Cochrane Oral Health Trials Register, CENTRAL, MEDLINE, Embase, two other databases and two trials registers up to 14 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) (both parallel-group and split-mouth design) in participants with a clinical diagnosis of periodontitis, peri-implantitis or peri-implant disease. We compared the adjunctive use of antimicrobial photodynamic therapy (aPDT), in which aPDT was given after subgingival or submucosal instrumentation (SI), versus SI alone or a combination of SI and a placebo aPDT given during the active or supportive phase of therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures, and we used GRADE to assess the certainty of the evidence. We prioritised six outcomes and the measure of change from baseline to six months after treatment: probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL), gingival recession (REC), pocket closure and adverse effects related to aPDT. We were also interested in change in bone level (for participants with peri-implantitis), and participant satisfaction and quality of life. MAIN RESULTS: We included 50 RCTs with 1407 participants. Most studies used a split-mouth study design; only 18 studies used a parallel-group design. Studies were small, ranging from 10 participants to 88. Adjunctive aPDT was given in a single session in 39 studies, in multiple sessions (between two and four sessions) in 11 studies, and one study included both single and multiple sessions. SI was given using hand or power-driven instrumentation (or both), and was carried out prior to adjunctive aPDT. Five studies used placebo aPDT in the control group and we combined these in meta-analyses with studies in which SI alone was used. All studies included high or unclear risks of bias, such as selection bias or performance bias of personnel (when SI was carried out by an operator aware of group allocation). We downgraded the certainty of all the evidence owing to these risks of bias, as well as for unexplained statistical inconsistency in the pooled effect estimates or for imprecision when evidence was derived from very few participants and confidence intervals (CI) indicated possible benefit to both intervention and control groups. Adjunctive aPDT versus SI alone during active treatment of periodontitis (44 studies) We are very uncertain whether adjunctive aPDT during active treatment of periodontitis leads to improvement in any clinical outcomes at six months when compared to SI alone: PPD (mean difference (MD) 0.52 mm, 95% CI 0.31 to 0.74; 15 studies, 452 participants), BOP (MD 5.72%, 95% CI 1.62 to 9.81; 5 studies, 171 studies), CAL (MD 0.44 mm, 95% CI 0.24 to 0.64; 13 studies, 414 participants) and REC (MD 0.00, 95% CI -0.16 to 0.16; 4 studies, 95 participants); very low-certainty evidence. Any apparent differences between adjunctive aPDT and SI alone were not judged to be clinically important. Twenty-four studies (639 participants) observed no adverse effects related to aPDT (moderate-certainty evidence). No studies reported pocket closure at six months, participant satisfaction or quality of life. Adjunctive aPDT versus SI alone during supportive treatment of periodontitis (six studies) We were very uncertain whether adjunctive aPDT during active treatment of periodontitis leads to improvement in any clinical outcomes at six months when compared to SI alone: PPD (MD -0.04 mm, 95% CI -0.19 to 0.10; 3 studies, 125 participants), BOP (MD 4.98%, 95% CI -2.51 to 12.46; 3 studies, 127 participants), CAL (MD 0.07 mm, 95% CI -0.26 to 0.40; 2 studies, 85 participants) and REC (MD -0.20 mm, 95% CI -0.48 to 0.08; 1 study, 24 participants); very low-certainty evidence. These findings were all imprecise and included no clinically important benefits for aPDT. Three studies (134 participants) reported adverse effects: a single participant developed an abscess, though it is not evident whether this was related to aPDT, and two studies observed no adverse effects related to aPDT (moderate-certainty evidence). No studies reported pocket closure at six months, participant satisfaction or quality of life. AUTHORS' CONCLUSIONS: Because the certainty of the evidence is very low, we cannot be sure if adjunctive aPDT leads to improved clinical outcomes during the active or supportive treatment of periodontitis; moreover, results suggest that any improvements may be too small to be clinically important. The certainty of this evidence can only be increased by the inclusion of large, well-conducted RCTs that are appropriately analysed to account for change in outcome over time or within-participant split-mouth study designs (or both). We found no studies including people with peri-implantitis, and only one study including people with peri-implant mucositis, but this very small study reported no data at six months, warranting more evidence for adjunctive aPDT in this population group.

Recent breakthroughs in graphene quantum dot-enhanced sonodynamic and photodynamic therapy.

Water-soluble graphene quantum dots (GQDs) have recently exhibited considerable potential for diverse biomedical applications owing to their exceptional optical and chemical properties. However, the pronounced heterogeneity in the composition, size, and morphology of GQDs poses challenges for a comprehensive understanding of the intricate correlation between their structural attributes and functional properties. This variability also introduces complexities in scaling the production processes and addressing safety considerations. Light and sound have firmly established their role in clinical applications as pivotal energy sources for minimally invasive therapeutic interventions. Given the limited penetration depth of light, photodynamic therapy (PDT) predominantly targets superficial conditions such as dermatological disorders, head and neck malignancies, ocular ailments, and early-stage esophageal cancer. Conversely, ultrasound-based sonodynamic therapy (SDT) capitalizes on its superior ability to propagate and focus ultrasound within biological tissues, enabling a diverse range of therapeutic applications, including the management of gliomas, breast cancer, hematological tumors, and modulation of the blood-brain barrier (BBB). Considering the advancements in theranostic and precision therapies, reevaluating these conventional energy sources and their associated sensitizers is imperative. This review introduces three prevalent treatment modalities that harness light and sound stimuli: PDT, SDT, and a synergistic approach that integrates PDT and SDT. This study delineated the therapeutic dynamics and contemporary designs of sensitizers tailored to these modalities. By exploring the historical context of the field and elucidating the latest design strategies, this review underscores the pivotal role of GQDs in propelling the evolution of PDT and SDT. This aspires to stimulate researchers to develop "multimodal" therapies integrating both light and sound stimuli.

Clinical efficacy of a new therapeutic option for lower genital tract lesions: 5-ALA photodynamic therapy.

The study utilized 5-ALA-PDT to treat patients with CIN or VaIN and assessed their clinical response, HPV clearance, and influencing factors after photodynamic therapy (PDT). This study involved 56 patients who received 5-ALA-PDT in a single center from May 2020 to March 2022, including 12 patients with CIN, 30 patients with VaIN, and 14 patients with both CIN and VaIN. Follow-up were conducted within 6 and 12 months after treatment to evaluate the clinical effectiveness of PDT. The assessment criteria included histological response (ER, elimination rate, RR, regression rate) and HPV clearance. Additionally, factors that could potentially influence the outcomes were analyzed. After PDT, the histological response showed an ER of 48.2% (27/56) and a RR of 80.4% (45/56) within 6 months of follow-up. The elimination rate increased to 69.6% (39/56) within 12 months, along with a regression rate of 82.1% (46/56). The rates of HPV clearance were observed to be 37.5% (21/56) and 44.6% (25/56) within 6 and 12 months, respectively. The study also revealed that HPV clearance significantly influenced histologic elimination within 6 months (p < 0.001) and histologic regression within 12 months (p < 0.01). Furthermore, premenopausal women exhibited a higher HPV clearance rate compared to postmenopausal women (61.5% vs. 30.0%, p = 0.036). 5-ALA PDT can be considered as an available option for the treatment of lower genital squamous intraepithelial lesions. The efficacy of its histologic response depends on HPV clearance. Additionally, it has been found that premenopausal women may benefit more from this treatment.

A Synergistic Strategy Combining Chemotherapy and Photodynamic Therapy to Eradicate Prostate Cancer.

Prostate cancer is the most prevalent cancer among men in the United States and is a leading cause of cancer-related death. Prostate specific membrane antigen (PSMA) has been established as a biomarker for prostate cancer diagnosis and treatment. This study aimed to develop a novel theranostic agent, PSMA-1-MMAE-Pc413, which integrates a PSMA-targeting ligand, the photosensitizer Pc413, and the microtubular inhibitor monomethyl auristatin E (MMAE) for synergistic therapeutic efficacy. In vitro uptake studies revealed that PSMA-1-MMAE-Pc413 demonstrated selective and specific uptake in PSMA-positive PC3pip cells but not in PSMA-negative PC3flu cells, with the uptake in PC3pip cells being approximately three times higher. In vitro cytotoxicity assays showed that, when exposed to light, PSMA-1-MMAE-Pc413 had a synergistic effect, leading to significantly greater cytotoxicity in PSMA-positive cells (IC50 = 2.2 nM) compared to PSMA-1-Pc413 with light irradiation (IC50 = 164.9 nM) or PSMA-1-MMAE-Pc413 without light irradiation (IC50 = 12.6 nM). In vivo imaging studies further demonstrated the selective uptake of PSMA-1-MMAE-Pc413 in PC3pip tumors. In in vivo studies, PSMA-1-MMAE-Pc413 dramatically improves the therapeutic outcome for prostate cancer by providing a synergistic effect that surpasses the efficacy of each treatment modality alone in PC3pip tumors. These findings suggest that PSMA-1-MMAE-Pc413 has strong potential for clinical application in improving prostate cancer treatment.

Advances and perspectives in phototherapy-based combination therapy for cancer treatment.

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has the advantages of spatiotemporal selectivity, non-invasiveness, and negligible drug resistance. Phototherapy has been approved for treating superficial epidermal tumors. However, its therapeutic efficacy is limited by the hypoxic tumor microenvironment and the highly expressed heat shock protein. Moreover, poor tissue penetration and focused irradiation laser region in phototherapy make treating deep tissues and metastatic tumors challenging. Combination therapy strategies, which integrate the advantages of each treatment and overcome their disadvantages, can significantly improve the therapeutic efficacy. Recently, many combination therapy strategies have been reported. Our study summarizes the strategies used for combining phototherapy with other cancer treatments such as chemotherapy, immunotherapy, sonodynamic therapy, gas therapy, starvation therapy, and chemodynamic therapy. Some research cases were selected to analyze the combination therapy effect, delivery platform feature, and synergetic anticancer mechanisms. Moreover, additional research cases are summarized in the tables. This review provides strong evidence that phototherapy-based combination strategies can enhance the anticancer effect compared with phototherapy alone. Additionally, the challenges and future perspectives associated with these combinational therapies are discussed.

Preliminary analysis of the efficacy of Mohs micrographic surgery combined with photodynamic therapy in a case of noninvasive extramammary Paget's disease.

PURPOSE: To evaluate the efficacy of Mohs micrographic surgery (MMS) combined with photodynamic therapy (PDT) in treating non-invasive extramammary Paget's disease (EMPD). MATERIALS AND METHODS: A 77-year-old male patient with non-invasive EMPD was treated with MMS followed by PDT. Preoperative fluorescence localization using 5-aminolevulinic acid (ALA) was performed to determine the surgical scope. MMS was conducted under lumbar anesthesia with intraoperative frozen-section pathology. Postoperative PDT was administered weekly for three sessions. RESULTS: The patient achieved negative surgical margins after two rounds of intraoperative pathology. Postoperative follow-up over two years showed no recurrence, and the patient did not experience significant adverse reactions. CONCLUSION: The combination of MMS and PDT was effective in treating non-invasive EMPD, demonstrating favorable clinical outcomes and no recurrence over the two-year follow-up period.

Multifunctional hydrogels based on photothermal therapy: A prospective platform for the postoperative management of melanoma.

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy.

Mitochondria-targeted polyprodrug nanoparticles induce mitochondrial stress for immunogenic chemo-photodynamic therapy of ovarian cancer.

Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.

Efficacy and Safety of the Modified Cretan Protocol in Patients with Post-LASIK Ectasia

Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE). Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment. Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 µm, and -0.21±0.63 µm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 µm, and -0.51±0.58 µm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up. Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.

TME-Triggered Degradable Phototheranostic Nanoplatform for NIR-II Fluorescence Bioimaging-Guided Phototherapies and Immune Activation.

The low therapeutic efficacy and potential long-term toxicity of antitumor treatments seriously limit the clinical application of phototherapies. Herein, we develop a degradable phototheranostic nanoplatform for NIR-II fluorescence bioimaging-guided synergistic photothermal (PTT) and photodynamic therapies (PDT) and immune activation to inhibit tumor growth. The phototheranostic nanoplatform (CX@PSS) consists of multidisulfide-containing polyurethane loaded with a photosensitizer CX, which can be specifically degraded in the GSH overexpressed tumor microenvironment (TME) and exhibits good NIR-II fluorescence, photodynamic, and photothermal properties. Under 808 nm light irradiation, CX@PSS exhibits efficient photothermal conversion and ROS generation, which further induces immunogenic cell death (ICD), releasing tumor-associated antigens and activating the immune response. In vitro and in vivo studies confirm the potential of CX@PSS in NIR II FL imaging-guided tumor treatments by synergistic PTT, PDT, and immune activation. This work is expected to provide a new pathway for clinical applications of imaging-guided tumor diagnosis and treatments.

HiPorfin photodynamic therapy for vaginal high-grade squamous intraepithelial lesion.

PURPOSE: We aimed to evaluate the efficacy and safety of HiPorfin-photodynamic therapy (PDT) in women with vaginal high-grade squamous intraepithelial Lesion (HSIL). METHODS: Retrospective analysis of eighteen patients with vaginal HSIL received HiPorfin-PDT between June 2019 and May 2023. Illumination with a 630-nm laser light was applied to the lesions 48-72 h after intravenous injection of 2 mg/kg HiPorfin®. The light dose to the lesions was 150 J/cm2. RESULTS: The mean age of the 18 patients was 45.8 years (range, 24 to 63). The complete response (CR) rate was 66.7% (12/18), 83.3% (15/18) and 83.3% (15/18) at 3, 6 and 12 months after PDT, respectively. Patients who achieved CR showed no signs of recurrence during long-term follow-up. There were three cases of persistent disease showing partial response (PR) and the lesion area was significantly reduced more than 50%. One patient with persistent disease then underwent thermocoagulation one time and subsequently showed no evidence of HSIL. Pre-treatment, 100% (18/18) patients were high-risk human papilloma virus (HR-HPV)-positive. HPV eradication rate was 16.7% (3/18), 22.2% (4/18) and 44.4% (8/18) after PDT at 3, 6 and 12 months, respectively. Before treatment, liquid-based cytology test ≥ atypical squamous cells of undetermined significance (ASCUS) was 94.4% (17/18). Negative conversion ratio of cytology was 47.1% (8/17), 52.9% (9/17) and 76.5% (13/17) at 3, 6 and 12 months, respectively. There were no serious adverse effects during and after PDT. CONCLUSIONS: HiPorfin-PDT may be an effective alternative treatment for vaginal HSIL for organ-saving and sexual function protection.

Biomimetic Ghost Nanomedicine-Based Optotheranostics for Cancer.

Theranostic medicine combines diagnostics and therapeutics, focusing on solid tumors at minimal doses. Optically activated photosensitizers are significant examples owing to their photophysical and chemical properties. Several optotheranostics have been tested that convert light to imaging signals, therapeutic radicals, and heat. Upon light exposure, conjugated photosensitizers kill tumor cells by producing reactive oxygen species and heat or by releasing cancer antigens. Despite clinical trials, these molecularly conjugated photosensitizers require protection from their surroundings and a localized direction for site-specific delivery during blood circulation. Therefore, cell membrane biomimetic ghosts have been proposed for precise and safe delivery of these optically active large molecules, which are clinically relevant because of their biocompatibility, long circulation time, bypass of immune cell recognition, and targeting ability. This review focuses on the role of biomimetic nanoparticles in the treatment and diagnosis of tumors through light-mediated diagnostics and therapy, providing insights into their preclinical and clinical status.