Application Of Photodynamic Therapy Research Articles

Acridinedione-phthalimide conjugates: Intramolecular electron transfer and singlet oxygen generation studies for optical and photodynamic therapy applications

We reported herein the synthesis, characterization of hybrid conjugates composed of phthalimide (Phth) and acridine-1,8-diones (Acr) for optical and medical applications. For the synthetic procedure, a three-step synthetic strategy has been utilized. The optical properties of the examined 1,8-acridinedione–phthalimide connected molecules (AcrPhth 1–5) have been examined utilizing various spectroscopic techniques, e.g., steady-state absorption and fluorescence, and time-correlated single photon counting. The steady-state absorption studies showed that AcrPhth 1–5 absorbs the light in the UV and visible region. The fluorescence studies of AcrPhth 1–5 exhibited significant fluorescence quenching compared to the acridinedione control compounds (Acr 1–5) suggesting the occurrence of electron-transfer reactions from the electron donating acridinedione moiety (Acr) to the electron accepting phthalimide moiety (Phth). The rate and efficiency of the electron-transfer reactions were determined from the fluorescence lifetime measurements indicating the fast electron-transfer processes of the covalently connected AcrPhth 1–5 conjugates. Computational studies supported the intramolecular electron-transfer reaction of AcrPhth conjugates using ab initio B3LYP/6-311G methods. In the optimized structures, the HOMO was found to be entirely located on the Acr entity, while the LUMO was found to be entirely on the Phth entity. Further, the synthesized compounds were tested as photosensitizers for generating the singlet oxygen species, which is a key factor in the photodynamic therapy (PDT) applications. The nanosecond laser flash measurements enable us to detect the triplet-excited states of examined Acr and AcrPhth conjugates, determining the triplet quantum yields, and direct detecting the singlet oxygen in an accurate way. From this observation, the singlet quantum yields were found to be in the range of 0.12–0.27 (for Acr 1–5) and 0.07–0.19 (for AcrPhth 1–5 conjugates). The molecular docking studies revealed that compound AcrPhth 2 exhibited high binding affinity with for key genes (p53, TOP2B, p38, and EGFR) suggesting its potential as a targeted anticancer therapy.Graphical abstractEfficient intramolecular electron-transfer reaction for the light harvesting conjugates! In addition, the conjugates can be used as good photosensitizers for PDT

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.

Self-Assembled Nanocomposite DOX/TPOR4@CB[7]4 for Enhanced Synergistic Photodynamic Therapy and Chemotherapy in Neuroblastoma.

DOX/TPOR4@CB[7]4 was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of photodynamic therapy on SH-SY5Y cells was assessed using the MTT assay, while flow cytometry analysis was employed to detect cell apoptosis. Confocal laser scanning microscopy was utilized to observe the intracellular distribution of DOX/TPOR4@CB[7]4 in SH-SY5Y cells. Additionally, fluorescence imaging of DOX/TPOR4@CB[7]4 in nude mice bearing SH-SY5Y tumors and examination of the combined effects of photodynamic and chemical therapies were conducted. The incorporation of CB[7] significantly enhanced the optical properties of DOX/TPOR4@CB[7]4, resulting in increased ROS production and pronounced toxicity towards SH-SY5Y cells. Moreover, both the apoptotic and mortality rates exhibited significant elevation. In vivo experiments demonstrated that tumor growth inhibition was most prominent in the DOX/TPOR4@CB[7]4 group. π-π interactions facilitated the binding between DOX and photosensitizer TPOR, with TPOR's naphthalene hydrophilic groups encapsulated within CB[7]'s cavity through host-guest interactions with CB[7]. Therefore, CB[7] can serve as a nanocarrier to enhance the combined application of chemical therapy and photodynamic therapy, thereby significantly improving treatment efficacy against neuroblastoma tumors.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Synthesis and evaluation of novel mitochondria-targeted, water-soluble phenoxazine-porphyrins for efficient photodynamic therapy

In this study, we use cationic imidazole as the targeting group and phenoxazine as the electron donor, attaching phenoxazine to porphyrin via two different linking methods to synthesize two phenoxazine-porphyrin photosensitizers (PSs), P1 and P2, intended for photodynamic therapy (PDT) applications. Additionally, we synthesized a molecule, P3, that does not contain the cationic imidazole group, to serve as a control PS. We comprehensively evaluate the performance of P1 and P2 through steady-state and transient spectroscopy analysis, theoretical calculations, photooxidation experiments, and in vitro cell experiments. The results showed that P1 and P2 exhibit excellent water solubility, longer triplet state lifetimes (P1 at 200 μs, P2 at 170 μs), outstanding photostability, higher photooxidation rates and quantum yields of singlet oxygen (1O2). Notably, in the photooxidation experiment, P1's photooxidation rate is 1.1 times that of P2, and 1.5 times that of tetraphenyl zinc porphyrin (ZnTPP) without phenothiazine. This may be due to the larger Gibbs free energy difference between the singlet and triplet excited states in P1 (ΔGS-T of P1 is 0.87 eV, compared to 0.83 eV for P2), which results in a greater driving force for intersystem crossing (ISC) in P1 than in P2. The introduction of the cationic imidazole group in P1 and P2 significantly enhances water solubility and tumor cell uptake compared to P3, particularly showing higher intracellular accumulation and 1O2 generation capabilities in HepG2 tumor cells. Flow cytometry test results further confirmed the significant photocytotoxicity of P1 and P2, with a marked decrease in survival rates after light exposure, where the survival rate of P1 nanoparticles (NPs) dropped to 41.7 %, P2 NPs to 35.1 %, and P3 NPs to 75.0 %. The findings of this study provide crucial theoretical support for the design of new PSs.

Dissecting Exciton Dynamics in pH-Activatable Long-Wavelength Photosensitizers for Traceable Photodynamic Therapy.

Tumor-specific activatable long-wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (Φ 1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH-activatable cyanine-based LW PSs (LET-R, R = H, Cl, Br, I), among which the activated LET-I exhibits strong light absorption at 808 nm and a remarkable 3.2-fold enhancement in Φ 1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual-modal imaging-escorted complete photodynamic eradication of tumors by the folic acid (FA)-modified LET-I probe (LET-I-FA), under the ultralow 808 nm laser power density (0.2 W cm-2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.

A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes

Metal complexes hold significant promise in tumor diagnosis and treatment. However, their potential applications in photodynamic therapy (PDT) are hindered by issues such as poor photostability, low yield of reactive oxygen species (ROS), and aggregation-induced ROS quenching. To address these challenges, we present a molecular self-assembly strategy utilizing aggregation-induced emission (AIE) conjugates for metal complexes. As a proof of concept, we synthesized a mitochondrial-targeting cyclometalated Ir(III) photosensitizer Ir-TPE. This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups. Ir-TPE readily self-assembles into nanoaggregates in aqueous solution, leading to a significant production of ROS upon light irradiation. Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria, resulting in mitochondrial DNA damage. This damage can lead to ferroptosis and autophagy, two forms of cell death that are highly cytotoxic to cancer cells. The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS, leading to a more pronounced cytotoxic effect. In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication. This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.

Thio and Seleno-Psoralens as Efficient Triplet Harvesting Photosensitizers for Photodynamic Therapy.

The Psoralen (Pso) molecule finds extensive applications in photo-chemotherapy, courtesy of its triplet state forming ability. Sulfur and selenium replacement of exocyclic carbonyl oxygen of organic chromophores foster efficient triplet harvesting with near unity triplet quantum yield. These triplet-forming photosensitizers are useful in Photodynamic Therapy (PDT) applications for selective apoptosis of cancer cells. In this work, we have critically assessed the effect of the sulfur and selenium substitution at the exocyclic carbonyl (TPso and SePso, respectively) and endocyclic oxygen positions of Psoralen. It resulted in a significant redshifted absorption spectrum to access the PDT therapeutic window with increased oscillator strength. The reduction in singlet-triplet energy gap and enhancement in the spin-orbit coupling values increase the number of intersystem crossing (ISC) pathways to the triplet manifold, which shortens the ISC lifetime from 10-5 s for Pso to 10-8 s for TPso and 10-9 s for SePso. The intramolecular photo-induced electron transfer process, a competitive pathway to ISC, is also considerably curbed by exocyclic functionalizations. In addition, a maximum of 115 GM of two-photon absorption (2PA) with IR absorption (660-1050 nm) confirms that the Psoralen skeleton can be effectively tweaked via single chalcogen atom replacement to design a suitable PDT photosensitizer.

Visible and Red Light-Triggered Anticancer Profile of a Ferrocene-Re(I)-Tricarbonyl Conjugate: Experimental and Theoretical Studies.

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 μM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.

Recent Advances in Photodynamic Therapy for Vascular Abnormalities.

Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects.

Sodium copper chlorophyllin conjugated with Ag plasmonic nanoparticles as efficient nanostructure for application in photodynamic therapy

Photodynamic therapy (PDT) is a method that uses light-sensitive photosensitizers to stimulate cells with specific wavelengths. Nanoparticles (NPs) are an emerging technology in PDT, offering advantages over classical photosensitizers. The amalgamation of silver NPs and photosensitizer drugs has gained significant attention in PDT. We conjugated Ag NPs to sodium-copper chlorophyllin (SCC) in this research. The binding of Ag NPs to SCC was examined using X-ray diffraction, SEM, EDS, DLS, Zeta potential, and FTIR analyses. The optical properties of SCC before and after binding toAg NPs were performed through Photoluminescence (PL) analysis and UV–visible spectroscopy, as well as the production of reactive oxygen species (ROS) and free radicals (hydroxyl radical) before and after binding through the photobleaching phenomenon of methylene blue and photochemical degradation of anthracene. SCC exhibits high absorption in the visible spectrum violet-blue (350–470 nm) and red (570–710 nm) regions. HeLa cells and red LED were used to investigate the cytotoxicity (MTT assay) of SCC attached to Ag NPs.

Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid.

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.

Fabrication of Carbon Dots with Singlet Oxygen Generation and Their Potential Photodynamic Therapy Applications.

Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example, bioimaging, fluorescence sensing, and drug delivery, etc. Recently, it was found that, under light excitation, CDs can also be exploited as a novel photosensitizer to prepare reactive oxygen species (ROS), which expand their applications in the field of photodynamic therapy for cancer treatment. Nevertheless, the high cost and complex fabrication approach of CDs significantly limit their applications. To address this issue, bottom-up routes usually utilize sustainable and inexpensive carbon precursor as starting materials, employed N,N-dimethylformamide (DMF) or ethanol as an environmental-friendly solvent. Bottom-up approach was energy efficient, and the purification process was relatively simple by dialysis. Therefore, carbon dots (CDs) were facilely fabricated in a one-pot solvothermal process using 1-aminoanthraquinone as a precursor, and their application as photosensitizers for in vitro antitumor cells, especially photodynamic therapy (PDT) was established. Then the photophysical and nanoscale dimensions properties of the fabricated CDs were characterized via TEM, UV-visible, fluorescence, and FT-IR spectroscopy. The synthesized N-doped CDs can easily dissolve in water, possess very low biotoxicity, yellow-light emission (maximum peak at 587nm). More importantly, PDT studies demonstrated that the obtained CDs possess a high singlet oxygen yield of 35%, and exhibit significant phototoxicity to cancer cells upon 635nm laser irradiation. These studies highlight that N-doped CDs can be facilely synthesized from only one precursor, and are a potentially novel theranostic agent for in vivo PDT.

Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Plants-occurring Anthraquinones as Photosensitive Compounds for Photodynamic Method: A Critical Overview.

The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.

Recent advances in biomimetic aggregation‐induced emission photosensitizers for photodynamic therapy and immunotherapy

AbstractThe development of novel photosensitizers (PSs) with aggregation‐induced emission (AIE) properties has emerged as a crucial advancement in the field of photodynamic therapy (PDT). However, the versatile applications of AIE PSs are limited by low encapsulation efficiency and inadequate target tissue permeability. Biomimetic technology stands out as a promising strategy to overcome these challenges, aiming to enhance AIE PSs tumor penetration efficacy, and their association with antitumor immune responses. In this review, recent advancements in biomimetic AIE PSs for PDT and immunotherapy are summarized. We start with introducing strategies involving biomimetic AIE PSs based on cell membranes and extracellular vesicles for the combined application of PDT and immunotherapy. We then discuss the preparation of biomimetic AIE PSs nanoparticles. Finally, we briefly outline the challenges and prospects associated with biomimetic AIE PSs.

Charge Transfer-Promoted Excited State of a Heavy-Atom-Free Photosensitizer for Efficient Application of Mitochondria-Targeted Fluorescence Imaging and Hypoxia Photodynamic Therapy.

Conventional photosensitizers (PSs) used in photodynamic therapy (PDT) have shown preliminary success; however, they are often associated with several limitations including potential dark toxicity in healthy tissues, limited efficacy under acidic and hypoxic conditions, suboptimal fluorescence imaging capabilities, and nonspecific targeting during treatment. In response to these challenges, we developed a heavy-atom-free PS, denoted as Cz-SB, by incorporating ethyl carbazole into a thiophene-fused BODIPY core. A comprehensive investigation into the photophysical properties of Cz-SB was conducted through a synergistic approach involving experimental and computational investigations. The enhancement of intersystem crossing (kISC) and fluorescence emission (kfl) rate constants was achieved through a donor-acceptor pair-mediated charge transfer mechanism. Consequently, Cz-SB demonstrated remarkable efficiency in generating reactive oxygen species (ROS) under acidic and low-oxygen conditions, making it particularly effective for hypoxic cancer PDT. Furthermore, Cz-SB exhibited good biocompatibility, fluorescence imaging capabilities, and a high degree of localization within the mitochondria of living cells. We posit that Cz-SB holds substantial prospects as a versatile PS with innovative molecular design, representing a potential "one-for-all" solution in the realm of cancer phototheranostics.

Compounding Methylene Blue with Selenium-decorated Graphene Quantum Dots to Improve Singlet Oxygen Production for Photodynamic Therapy Application.

Graphene quantum dots (GQDs) are known as suitable material to be applied in different fields such as photodynamic therapy (PDT). Herein, GQDs were synthesized by the pyrolysis method and then decorated with selenium (Se). Afterward, they were combined with methylene blue (MB) to increase singlet oxygen generation as well as to apply them more effectively in the PDT method. Furthermore, GQDs were investigated by transmission electron microscope (TEM), photoluminescence spectrum (PL), Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), reactive oxygen species (ROS) measurement, and cytotoxicity measurement. GQDs showed no dependence on the excitation wavelength. The result of ROS measurement proves that the combination of GQD-Se and MB increases singlet oxygen production. Moreover, afterglow measurement approved the beneficial effect of GQD-Se on even deep and near skin tumor treatment. Cytotoxicity measurements under dark conditions, cell viability, and the side effects on human cells were determined by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay. Our findings show that under dark conditions, even high concentrations of nanoparticles have no significant effect on cell viability. These findings and the high biocompatibility of GQDs indicate the effective application of GQD-Se-MB in PDT.

Cell Membrane-Coated Biomimetic Nanoparticles in Cancer Treatment.

Nanoparticle-based drug delivery systems hold promise for cancer treatment by enhancing the solubility and stability of anti-tumor drugs. Nonetheless, the challenges of inadequate targeting and limited biocompatibility persist. In recent years, cell membrane nano-biomimetic drug delivery systems have emerged as a focal point of research and development, due to their exceptional traits, including precise targeting, low toxicity, and good biocompatibility. This review outlines the categorization and advantages of cell membrane bionic nano-delivery systems, provides an introduction to preparation methods, and assesses their applications in cancer treatment, including chemotherapy, gene therapy, immunotherapy, photodynamic therapy, photothermal therapy, and combination therapy. Notably, the review delves into the challenges in the application of various cell membrane bionic nano-delivery systems and identifies opportunities for future advancement. Embracing cell membrane-coated biomimetic nanoparticles presents a novel and unparalleled avenue for personalized tumor therapy.

Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 μM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.