Combination Of Photodynamic Therapy Research Articles

Microfluidic-Assisted Silk Nanoparticles Co-Loaded with Epirubicin and Copper Sulphide: A Synergistic Photothermal–Photodynamic Chemotherapy Against Breast Cancer

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a promising non-invasive cancer treatment, addressing issues like drug resistance and systemic toxicity common in conventional breast cancer therapies. Recent research has shown that copper sulphide (CuS) nanoparticles and polydopamine (PDA) exhibit exceptional photothermal conversion efficiency under 808 nm near-infrared (NIR) laser irradiation, making them valuable for cancer phototherapy. However, the effectiveness of PDT is limited in hypoxic tumour environments, which are common in many breast cancer types, due to its reliance on local oxygen levels. Moreover, single-modality approaches, including phototherapy, often prove insufficient for complete tumour elimination, despite their therapeutic strength. In this paper, a microfluidic-assisted approach was used to create multifunctional silk-based nanoparticles (SFNPs) encapsulating the chemotherapeutic drug Epirubicin (EPI), the PTT/PDT agent CuS, and the heat-activated, oxygen-independent alkyl radical generator AIPH for combined chemotherapy, PTT, and PDT, with a polydopamine (PDA) coating for enhanced photothermal effects and surface-bound folic acid (FA) for targeted delivery in breast cancer treatment. The synthesised CuS-EPI-AIPH@SF-PDA-FA nanoparticles achieved a controlled size of 378 nm, strong NIR absorption, and high photothermal conversion efficiency. Under 808 nm NIR irradiation, these nanoparticles selectively triggered the release of alkyl radicals and EPI, improving intracellular drug levels and effectively killing various breast cancer cell lines while demonstrating low toxicity to non-cancerous cells. We demonstrate that novel core–shell CuS-EPI-AIPH@SF-PDA-FA NPs have been successfully designed as a multifunctional nanoplatform integrating PTT, PDT, and chemotherapy for targeted, synergistic breast cancer treatment.

Nanoparticle-Mediated Cuproptosis and Photodynamic Synergistic Strategy: A Novel Horizon for Cancer Therapy.

Photodynamic therapy (PDT) is a noninvasive cancer treatment that works by using light to stimulate the production of excessive cytotoxic reactive oxygen species (ROS), which effectively eliminates tumor cells. However, the therapeutic effects of PDT are often limited by tumor hypoxia, which prevents effective tumor cell elimination. The oxygen (O2) consumption during PDT can further exacerbate hypoxia, leading to post-treatment adverse events. This review aims to explore the potential of cuproptosis, a recently discovered copper-dependent form of programmed cell death, to enhance the anticancer effects of PDT. Cuproptosis is highly dependent on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle, and can increase O2 and ROS levels or decrease glutathione (GSH) levels, thereby improving PDT outcomes. The review discusses the latest research advancements in the field, detailing the mechanisms that regulate cuproptosis and PDT. It also explores how nanoparticle (NP)-based strategies can be used to exploit the synergistic potential between cuproptosis and PDT. The article examines the prospects of synergistic anticancer activity guided by nanodelivery systems, which could overcome the challenges associated with hypoxia in cancer treatment. The combination of cuproptosis and PDT, facilitated by NP-based delivery systems, presents a promising approach to enhance the effectiveness of cancer therapy. The review concludes by discussing the challenges and future research directions for this combination therapy, highlighting the need for further investigation into the mechanisms and optimization of treatment strategies to improve outcomes in cancer treatment.

Rational design of AIEgens through π-bridge engineering for dual-modal photodynamic and photothermal therapy.

A series of aggregation-induced emission luminogens (AIEgens) with donor-π-acceptor (D-π-A) architecture were rationally designed and synthesized through π-bridge engineering for dual-modal photodynamic and photothermal therapy. The AIEgens (TPT, TFT, and TTT) were constructed using methoxy-substituted tetraphenylene as the electron donor and tricyanofuran as the electron acceptor, connected via different π-bridges (phenyl, furan, or thiophene). These compounds exhibited red-shifted absorption (460-545nm) and emission (712-720nm) with remarkable aggregation-induced emission characteristics. Among them, TTT demonstrated superior photophysical properties and was successfully encapsulated into amphiphilic calixarene-based nanoparticles (T@Q NPs) with uniform morphology. The T@Q NPs showed efficient reactive oxygen species generation and photothermal conversion (η=6.98%), enabling effective tumor cell ablation through combined photodynamic and photothermal therapy. In vivo studies revealed that T@Q NPs achieved 70% tumor growth inhibition in 4T1 tumor-bearing mice without obvious systemic toxicity. This work presents an effective strategy for designing AIEgens-based phototherapeutic agents through π-bridge engineering, offering promising candidates for clinical translation in tumor phototherapy.

Cryoshocked Adipocytes Mediated Dual-Modal Strategy Combining Photodynamic Therapy and Triptolide Palmitate for Pulmonary Metastatic Melanoma Treatment.

Pulmonary metastasis represents one of the most prevalent forms of metastasis in advanced melanoma, with mortality rates reaching 70%. Current treatments including chemotherapy, targeted therapy, and immunotherapy frequently exhibit limited efficacy or present high costs. To address these clinical needs, this study presents a biomimetic drug delivery system (Ce6-pTP-CsA) utilizing cryoshocked adipocytes (CsA) encapsulating the prodrug triptolide palmitate (pTP) and the photosensitizer Ce6, exploiting the characteristic of tumor cells to recruit and lipolyze adipocytes for energy. CsA substantially enhances the drug-loading capacity of adipocytes, with its particle size characteristics enabling targeted delivery of pTP to the lungs. The combination of photodynamic therapy (PDT) and pTP activates the caspase cascade, promoting apoptosis in tumor cells. Notably, the cleavage of disulfide bonds in pTP depletes glutathione (GSH), reducing its scavenging effect on reactive oxygen species (ROS) and enhancing the efficacy of PDT. Results demonstrate that Ce6-pTP-CsA effectively inhibits the proliferation and invasion of pulmonary metastatic melanoma cells in vitro and induces apoptosis, while significantly suppressing lung metastasis of SCID mice models in vivo. In conclusion, this novel biomimetic drug delivery system based on adipocytes provides a promising strategy for targeted therapy in pulmonary metastatic melanoma.

Photodynamic therapy as a strategic ally in radiotherapy for triple-negative breast cancer: the importance of treatment order.

Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models. In vitro, PDT was combined with RT (2.5Gy) using a porphyrin (TMPyP, 32 μmolL-1) and red light (660 ± 15nm) with a dose of 50 Jcm-2. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels. Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response. Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.

NIR photo-responsive injectable chitosan/hyaluronic acid hydrogels with controlled NO release for the treatment of MRSA infections.

Due to resistance to common antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) infections pose a significant threat to human health. In this study, we developed an injectable, adhesive, and biocompatible hydrogel with multiple functions. Specifically, carboxymethyl chitosan (CMCS) crosslinked with hyaluronic acid (HA) forms the primary framework of the hydrogel. Subsequently, polydopamine (PDA), 5,10,15,20-tetrakis (4-aminophenyl) porphyrin (TAPP), and L-arginine (L-Arg) are incorporated as a photothermal agent, photosensitizer, and nitric oxide (NO) donor, respectively, resulting in the CHDTA hydrogel. Under the combined irradiation of 660 nm and 808 nm near-infrared (NIR) light, the CHDTA hydrogel exhibits both photodynamic therapy (PDT) and photothermal therapy (PTT) effects. Simultaneously, L-Arg reacts with singlet oxygen (1O2), generated via the PDT effect, leading to the production of NO. The CHDTA hydrogel effectively inhibits the activity of Staphylococcus aureus (S. aureus) and MRSA, achieving bactericidal rates of 99.4 % and 98.8 %, respectively, through a combination of PDT, PTT, and NO synergistic antibacterial mechanisms. In vivo studies demonstrate the excellent antibacterial properties and wound healing promotion of the CHDTA hydrogel in MRSA-infected animal wound models. The hydrogel system developed in this study integrates multiple functional design concepts and serves as a potential therapeutic platform for combating MRSA infections.

Nucleolus-Targeting Carbon Dot Nanocomplexes for Combined Photodynamic/Photothermal Therapy.

The low cure rate and high mortality associated with cancer pose significant threats to human health. Photodynamic and photothermal therapies have emerged as promising treatment strategies for various types of cancers. In this study, we successfully synthesized a novel type of carbon dot (CD) using 1,2,4-aminobenzene and ethylenediamine as precursors. Surprisingly, these CDs exhibited outstanding nucleolus-targeting capabilities coupled with a remarkable photothermal effect. Through the integration of these nucleolus-targeting CDs with indocyanine green (ICG) and folic acid (FA), we created CDs-ICG-FA nanocomplexes suitable for combined photodynamic and photothermal therapy. In vitro experiments demonstrated that CDs-ICG-FA maintained a robust photothermal ability, achieving a conversion efficiency of up to 34.3%. Furthermore, CDs-ICG-FA generated abundant reactive oxygen species, effectively inducing cancer cell death and demonstrating its potential for photodynamic therapy. In MCF-7 cancer cells, CDs-ICG-FA exhibited a pronounced synergistic photothermal/photodynamic anticancer effect. Subsequent in vivo experiments in mice revealed that CDs-ICG-FA could selectively accumulate at tumor sites, significantly inhibiting tumor growth upon exposure to an 808 nm laser. These findings suggest that the developed nucleolus-targeting CDs-ICG-FA hold promising potential for cancer targeting and the application of combined photothermal/photodynamic therapy.

Comparative analysis of combined methylene blue photodynamic therapy and doxorubicin treatment of oral squamous cell carcinoma cell line: In vitro study on apoptosis.

Squamous cell carcinoma (SCC) is the most common malignancy of the head and neck region. Combination therapy potentially enhances the effectiveness beyond that of each treatment alone. This study aimed to assess whether photodynamic therapy (PDT), using methylene blue as a photosensitizer in conjunction with doxorubicin, produces synergistic effects on the apoptosis of the oral squamous cell carcinoma (OSCC) cell line. The human oral epidermal carcinoma cell line (KB cell line, NCBI Code: C152) was cultured in Dulbecco's modified Eagle's medium. Following at least 24 hours of incubation, the OSCC cells were distributed into six groups, with groups 1-3 and 5 performed in the dark to prevent any light interference. 1: control group; 2: treated with 3.2 μg/mL methylene blue; 3: exposed to various concentrations of doxorubicin; 4: PDT group (methylene blue + 660 nm light); 5: treated with both doxorubicin and methylene blue; and finally, 6: treated with PDT (methylene blue + 660 nm light) in conjunction with doxorubicin. Flow cytometry methods were used to assess apoptosis. Analysis of variance (ANOVA) was used to compare quantitative variables between groups, and Tukey's test was applied for pairwise group comparisons. Flow cytometry analysis revealed that the highest level of cellular apoptosis occurred in the group treated with PDT in conjunction with doxorubicin. PDT using the photosensitizer methylene blue, in combination with doxorubicin, can serve as an effective agent for inducing apoptosis in OSCC cells.

Comparison of the Efficacy of Photodynamic Therapy Versus Cisplatin Application

Introduction: Photodynamic therapy (PDT) is a photochemical treatment that involves the use of light and photosensitizer. This method is applied as a therapeutic approach against several types of cancer. The main aim of this study is to compare the efficacy of PDT with that of cisplatin (a well-known chemotherapy agent) through protein-protein interaction (PPI) network analysis. Methods: Gene expression profiles of human melanoma A375 cells from the Gene Expression Omnibus (GEO) were selected for analysis via directed PPI network analysis. The significant differentially expressed genes (DEGs) were identified and assessed based on co-expression interactions. The critical DEGs were introduced by considering out-degree and in-degree values. Results: Two directed PPI networks for upregulated and downregulated DEGs were constructed. TP53 was identified as a critical upregulated gene in response to cisplatin in comparison with PDT. EGFR, PPARG, MMP9, PTGS2, FOXO1, and RUNX2 were highlighted as the crucial downregulated genes due to the effect of cisplatin on the gene expression of the treated cells. Conclusion: Cisplatin directly targets key cellular functions such as cell growth, differentiation, migration, and invasion. It seems that the combination of cisplatin and PDT is a suitable method for treating cancers because cisplatin targets the key genes responsible for cancer development, while PDT intensifies the effect of cisplatin and reduces its side effects.

Biocompatible nanoparticles self-assembled by PEGylated polyphosphoesters for combination of photodynamic therapy and hypoxia-activated chemotherapy against breast cancer

IntroductionAlthough photodynamic therapy (PDT) shows considerable potential for cancer treatment due to its precise spatial control and reduced toxicity, effectively eliminating residual cells under hypoxic conditions remains challenging because of the resistance conferred by these cells.MethodsHerein, we synthesize an amphiphilic PEGylated polyphosphoester and present a nanocarrier (NPCT) specifically designed for the codelivery of hydrophobic photosensitizer (chlorin e6, Ce6) and hypoxia-activated prodrugs (tirapazamine, TPZ). We investigate the antitumor effect of NPCT on both cellular and animal level.ResultsThe efficient encapsulation of Ce6 and TPZ by NPCT enables the prolonged blood circulation and improved tumor distribution of both agents. Upon internalization by tumoral cells, 660 nm laser irradiation activates Ce6, leading to the generation of reactive oxygen species (ROS) that effectively kill murine 4T1 breast cancer cells. Meanwhile, the PDT process consumes a large amount of oxygen to generate the hypoxic microenvironment that activates the liberated TPZ from NPCT. The resulting highly cytotoxic radicals specifically target and induce cytotoxicity in remaining hypoxic cancer cells. Compared to other groups, the combination of NPCT and 660 nm laser irradiation resulted in the most substantial tumor growth inhibition.DiscussionThis innovative approach provides new avenues for the development of advanced delivery systems based on polyphosphoesters and combination therapeutic strategies.

Recent Advances in Porphyrin-Based Covalent Organic Frameworks for Synergistic Photodynamic and Photothermal Therapy.

Porphyrin's excellent biocompatibility and modifiability make it a widely studied photoactive material. However, its large π-bond conjugated structure leads to aggregation and precipitation in physiological solutions, limiting the biomedical applications of porphyrin-based photoactive materials. It has been demonstrated through research that fabricating porphyrin molecules into nanoscale covalent organic frameworks (COFs) structures can circumvent issues such as poor dispersibility resulting from hydrophobicity, thereby significantly augmenting the photoactivity of porphyrin materials. Porphyrin-based COF materials can exert combined photodynamic and photothermal effects, circumventing the limitations of photodynamic therapy (PDT) due to hypoxia and issues in photothermal therapy (PTT) from heat shock proteins or the adverse impact of excessive heat on the protein activity of normal tissue. Furthermore, the porous structure of porphyrin COFs facilitates the circulation of oxygen molecules and reactive oxygen species and promotes sufficient contact with the lesion site for therapeutic functions. This review covers recent progress regarding porphyrin-based COFs in treating malignant tumors and venous thrombosis and for antibacterial and anti-inflammatory uses via combined PDT and PTT. By summarizing relevant design strategies, ranging from molecular design to functional application, this review provides a reference basis for the enhanced phototherapy application of porphyrin-based COFs as photoactive materials. This review aims to offer valuable insights for more effective biomedical applications of porphyrin-based COFs through the synthesis of existing experimental data, thereby paving the way for their future preclinical utilization.

Enhancing anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy: A meta-analysis.

Anti-vascular endothelial growth factor (VEGF) agents administered as either monotherapy or combination with verteporfin photodynamic therapy (PDT) are the 2 dominant treatment for polypoidal choroidal vasculopathy (PCV); However, controversies remain due to small sample sizes and inconsistency in prognosis from randomized controlled trials (RCTs). In accordance with the PRISMA statement, we investigated the efficacy of PDT plus anti-VEGF combination with anti-VEGF monotherapy. This study was accepted by the International Prospective Register of Systematic Reviews (CRD42023471362). Studies published up to July, 2024, were retrieved from PubMed, Embase, and Cochrane databases. A total of 7 RCTs with 926 eyes were reviewed. In 6 trials, combination therapy showed significantly higher rate of complete polyp regression (risk ratio [RR]: 1.56, 95% CI: 1.15-2.13, p = 0.005). In 5 trials, combination therapy also significantly reduced the number of anti-VEGF injections (SMD: -0.65, 95% CI: -0.95 to -0.35, p < 0.0001). For best corrected visual acuity improvement, central retinal thickness reduction, and rate of ocular adverse events, the performance of the 2 modalities were comparable. We conclude that PDT plus anti-VEGF combination therapy constitutes a safe and effective modality and should be considered the first-line treatment for PCV.

Research progress of photodynamic therapy in antitumor therapies

Abstract. As one of the leading causes of disease death globally, conventional treatments for cancers have been developed, including surgery, chemotherapy, radiotherapy etc. However, some drawbacks restrain their therapeutic effects. Consequently, researchers have been struggling to develop novel strategies to cure tumors. Photodynamic therapy (PDT) is a significant means that utilizes light as well as photosensitizers to kill tumor cells. In PDT, a photosensitizer absorbs a photon and transfer to states with higher energy, then energy is released and generates free radicals and ground-state molecular oxygen by two distinct types of reaction to exert therapeutic functions. This review concentrates on the antitumor principles and mechanisms of PDT, common photosensitizers, combination of PDT and other cancer therapies and its effects on several typical cancers.

Research progress of photodynamic therapy in the anti-tumor field

Abstract. Photodynamic therapy (PDT), which is based on activating photosensitizers by light of a certain wavelength to produce anti-tumor effects, has attracted much attention because of its non-invasiveness and high selectivity for tumors. In many tumor diseases with high mortality rates, PDT has achieved better therapeutic effects when combined with a variety of therapies and has become one of the most important methods for treating a variety of cancers. In this review, we have collected research on the application of PDT in cancer and its combination with chemotherapy, immunotherapy, and nanomaterials in recent years, aiming to show that the combination of PDT with other therapies deserves further exploration

Disruption of Ferroptosis Inhibition and Immune Evasion with Tumor-Activatable Prodrug for Boosted Photodynamic/Chemotherapy Eradication of Drug-Resistant Tumors.

Breast cancer is a malignant tumor that threatens the life and health of women worldwide. As the first-line chemotherapy drug for breast cancer, doxorubicin (DOX) can inhibit the synthesis of RNA and DNA, and it exhibits strong inhibitory activity against breast cancer. However, drug-induced systemic toxicity and drug resistance can occur with DOX treatment. In this work, TSPO protein is identified as a promising target for overcoming drug resistance and we designed a novel BT-DOX/PDP conjugate to solve these problems in drug chemotherapy. It is found that BT-DOX/PDP can effectively downregulate TSPO1 protein and sensitize MCF-7/Adr to DOX. Furthermore, due to its positive charge, BT-DOX/PDP is readily loaded into puerarin (PUE), the resulting BT-DOX/PDP@PUE exhibited minimal systemic toxicity but enhanced antitumor activity in animal models, as compared with BT-DOX/PDP. This study demonstrates the advantages of combined chemotherapy and photodynamic therapy in overcoming drug resistance, which may be applied in the design of other photodynamic therapy-based conjugates to enhance antitumor therapy.

Hypocrellin: A Natural Photosensitizer and Nano-Formulation for Enhanced Molecular Targeting of PDT of Melanoma.

Nano-formulation has generated attention in the battle against cancer, because of its great flexibility, reduced adverse side effects, and accuracy in delivering drugs to target tissues dependent on the size and surface characteristics of the disease. The field of photodynamic treatment has advanced significantly in the past years. Photodynamic techniques that use nano-formulations have surfaced to further the field of nanotechnology in medicine, especially in cancer treatment. The pharmaceutical industry is seeing a growing trend toward enhanced drug formulation using nano-formulations such as liposomes, polymeric nanoparticles, dendrimers, nano-emulsions, and micelles. Natural extracts have also shown adverse effects when employed as photosensitizers in cancer therapy because they are cytotoxic when activated by light. Still, natural photosensitizers are a big part of cancer treatment. However, some shortcomings can be minimized by combining nano-formulations with these natural photosensitizers. The synergistic improvement in medication delivery that maintains or increases the mechanism of cell death in malignant cells has also been demonstrated by the combination of photodynamic therapy with nano-formulations and natural photosensitizers. Lastly, this review assesses the feasibility and potential of a photodynamic therapy system based on nano-formulations and natural photosensitizers in clinical treatment applications and briefly discusses the removal of toxic compounds associated with nano-formulations within cells.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid and Fractional CO2 Laser for the Management of Recalcitrant Plantar Warts

SignificancePlantar warts, benign lesions on the soles of the feet, are caused by the human papillomavirus (HPV) infecting keratinocytes. Complete eradication of these warts is challenging, often leading to recurrences. This study evaluates the combined clinical efficacy of topical 5-aminolevulinic acid (5-ALA) photodynamic therapy (PDT) and fractional carbon dioxide (CO2) laser treatment for recalcitrant plantar warts. ApproachData from 10 patients with recalcitrant plantar warts were analyzed. Initially, thickened hyperkeratotic tissue was removed using a super-pulsed CO2 laser. This was followed by fractional laser application, after which a 20% 5-ALA cream was applied occlusively for 4 hours. Patients then received He-Ne laser irradiation for 30 minutes at an energy density of 100 mW/cm², with treatments spaced 4 weeks apart. ResultsThe study included 10 participants aged 24 to 53 years (mean age: 33.4 ± 8.09 years). In total, 40 lesions were treated across 1 to 9 PDT sessions, with an average of 5.2 ± 2.86 sessions per patient. Complete clearance was achieved in 3 patients (30%), 4 patients (40%) showed an excellent response (≥80% improvement), while 2 patients had a partial response. One patient (10%) showed <50% improvement. The overall clearance rate was 70% (28 out of 40 lesions). Aside from temporary pain during the procedure and mild erythema post-treatment, one patient developed localized proliferative scarring. After a one-year follow-up, only one patient experienced recurrence. ConclusionsThe combination of 5-ALA PDT and fractional CO2 laser therapy shows promise as an effective and safe alternative for treating persistent plantar warts.

Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging

Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.

Combined use of 5-ALA-induced protoporphyrin IX and chlorin e6 for fluorescence diagnostics and photodynamic therapy of skin tumors.

Different types of photosensitizers (PSs) have different dynamics and intensities of accumulation, depending on the type of tumor or different areas within the same tumor. This determines the effectiveness of fluorescence diagnostics and photodynamic therapy (PDT). This paper studies the processes of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) and chlorin e6 (Ce6) accumulation in the central and border zones of a tumor after combined administration of two PSs into the patient's body. Fluorescence diagnostic methods have shown that sublingual administration of 5-ALA leads to the more intense accumulation of PpIX in a tumor compared to oral administration. Differences have been identified in the dynamics of 5-ALA-induced PpIX and Ce6 accumulation in the central and border zones of the tumor, as well as normal tissues. Ce6 accumulates mainly in the central zone of the tumor while PpIX accumulates in the border zone of the tumor. All patients with combined PDT experienced complete therapeutic pathomorphosis and relapse-free observation.

Dual-Mode Reactive Oxygen Species-Stimulated Carbon Monoxide Release for Synergistic Photodynamic and Gas Tumor Therapy.

Controllable carbon monoxide (CO) release simulated by light-generated reactive oxygen species (ROS) represents a promising approach for cancer therapy but is hampered by low CO release rate and low ROS generation of conventional photosensitizers in hypoxia tumor microenvironments. In this study, we developed a highly efficient nanoplatform (TPyNO2-FeCO NPs) through co-encapsulating organic AIE photosensitizers (PSs) and CO prodrug (Fe3(CO)12), which are capable of light-triggered robust ROS generation and CO release for synergistic photodynamic therapy (PDT) and CO gas therapy. The success of this nanoplatform leverages the design of a PS, TPyNO2, with exceptional type I and type II ROS generation capabilities, achieved through the introduction of the α-photoinduced electron transfer (α-PET) process. With the incorporation of a 4-nitrobenzyl unit as a typical PET donor, the intramolecular α-PET process not only suppresses the radiative decay to redirect the excited-state energy to intersystem crossing for more triplet-state formation but also promotes electron separation and transfer processes for radical-type ROS generation. The resultant TPyNO2 demonstrates superior singlet oxygen, superoxide anion, and hydroxyl radial generation capabilities in the aggregate state. Upon light irradiation, TPyNO2-FeCO NPs release CO via the type I and type II dual-mode ROS-mediated processes in a controlled and targeted manner, overcoming the limitations of conventional CO release systems. TPyNO2-FeCO NPs also demonstrate a self-accelerating ROS-CO-ROS loop as the released CO induces intracellular oxidative stress, depolarizes mitochondria membrane potentials, and inhibits ATP production, leading to further intracellular ROS generation. Both in vitro and in vivo experiments validated the excellent antitumor performance of the combined PDT and CO gas therapy. This study provides valuable insights into the development of advanced PSs and establishes TPyNO2-FeCO NPs as promising nanoplatforms for safe and effective antitumor applications.