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Journal of Medicinal Chemistry Jun 2024In this work, a set of quasi-intrinsic photosensitizers are theoretically proposed based on the...
In this work, a set of quasi-intrinsic photosensitizers are theoretically proposed based on the 2-amino-8-(1'-β-d-2'-deoxyribofuranosyl)-imidazo[1,2-α]-1,3,5-triazin-4(8H)-one (P), which could pair with the 6-amino-5-nitro-3-(1'-β-d-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and keep the essential structural characters of nucleic acid. It is revealed that the ring expansion and electron-donating/electron-withdrawing substitution bring enhanced two-photon absorption and bright photoluminescence of these monomers, thereby facilitating the selective excitation and tumor localization through fluorescence imaging. However, instead of undergoing radiative transition (S → S), the base pairing induced fluorescence quenching and rapid intersystem crossing (S → T) are observed and characterized by the reduced singlet-triplet energy gaps and large spin-orbit coupling values. To ensure the phototherapeutic properties of the considered base pairs in long-lived T state, we examined the vertical electron affinity as well as vertical ionization potential for production of superoxide anions via Type I photoreaction, and their required T energy (0.98 eV) to generate singlet oxygen O via Type II mechanism.
Topics: Photosensitizing Agents; Photochemotherapy; Humans; Photons; Optical Imaging; Animals; Drug Design; Mice; Molecular Structure
PubMed: 38815214
DOI: 10.1021/acs.jmedchem.4c00191 -
Langmuir : the ACS Journal of Surfaces... Jun 2024We 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 ,...
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 , [Re(Fctp)(CO)Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. 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 , which is helpful for PDT. 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, 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. produced more than 20 times higher phototoxicity (IC ∼1.5 μM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue , [Re(CO)(tp)Cl], where tp = 2,2':6',2″-terpyridine. induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC/IC) and selectivity index (SI, SI = normal cell's IC/cancer cell's IC) in the range of 25-33.
Topics: Ferrous Compounds; Humans; Metallocenes; Light; Antineoplastic Agents; Reactive Oxygen Species; Density Functional Theory; Photochemotherapy; Photosensitizing Agents; Coordination Complexes; Cell Line, Tumor; Drug Screening Assays, Antitumor; Red Light
PubMed: 38814099
DOI: 10.1021/acs.langmuir.4c01296 -
Current Opinion in Ophthalmology Jul 2024The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV). (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV).
RECENT FINDINGS
Improved understanding and diagnostic criteria among clinicians have led to advancements in the characterization of corneal NV and objective assessment of treatment response through ancillary imaging devices. Developments in corneal NV treatments, such as antivascular endothelial growth factor, fine needle diathermy, and photodynamic therapy, have improved treatment success rates and visual outcomes. More recent surgical treatment advancements include corneal cross-linking, endothelial keratoplasty, and mitomycin intravascular chemoembolization. Finally, a greater appreciation of the molecular pathogenesis and angiogenic factors involved in corneal NV has identified numerous potential targeted therapies in the future.
SUMMARY
The management of corneal NV has evolved to include several standalone and combination medical and surgical options. Additionally, improvements in quantifying corneal NV and understanding its molecular basis have contributed to new management strategies with improved outcomes.
Topics: Humans; Corneal Neovascularization; Angiogenesis Inhibitors; Photochemotherapy; Vascular Endothelial Growth Factor A
PubMed: 38813739
DOI: 10.1097/ICU.0000000000001049 -
ACS Applied Materials & Interfaces Jun 2024Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after...
Metastasis and recurrence are notable contributors to mortality associated with breast cancer. Although immunotherapy has shown promise in mitigating these risks after conventional treatments, its effectiveness remains constrained by significant challenges, such as impaired antigen presentation by dendritic cells (DCs) and inadequate T cell infiltration into tumor tissues. To address these limitations, we developed a multifunctional nanoparticle platform, termed GM@P, which consisted of a hydrophobic shell encapsulating the photosensitizer MHI148 and a hydrophilic core containing the STING agonist 2'3'-cGAMP. This design elicited robust type I interferon responses to activate antitumor immunity. The GM@P nanoparticles loaded with MHI148 specifically targeted breast cancer cells. Upon exposure to 808 nm laser irradiation, the MHI148-loaded nanoparticles produced toxic reactive oxygen species (ROS) to eradicate tumor cells through photodynamic therapy (PDT). Notably, PDT stimulated immunogenic cell death (ICD) to foster the potency of antitumor immune responses. Furthermore, the superior photoacoustic imaging (PAI) capabilities of MHI148 enabled the simultaneous visualization of diagnostic and therapeutic procedures. Collectively, our findings uncovered that the combination of PDT and STING activation facilitated a more conducive immune microenvironment, characterized by enhanced DC maturation, infiltration of CD8 T cells, and proinflammatory cytokine release. This strategy stimulated local immune responses to augment systemic antitumor effects, offering a promising approach to suppress tumor growth, inhibit metastasis, and prevent recurrence.
Topics: Photochemotherapy; Animals; Mice; Photosensitizing Agents; Membrane Proteins; Female; Humans; Nanoparticles; Reactive Oxygen Species; Breast Neoplasms; Cell Line, Tumor; Neoplasm Metastasis; Neoplasm Recurrence, Local; Dendritic Cells; Mice, Inbred BALB C; Nucleotides, Cyclic
PubMed: 38813586
DOI: 10.1021/acsami.4c02528 -
Frontiers in Bioscience (Landmark... May 2024Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its...
BACKGROUND
Due to its non-invasive and widely applicable features, photodynamic therapy (PDT) has been a prominent treatment approach against cancer in recent years. However, its widespread application in clinical practice is limited by the dark toxicity of photosensitizers and insufficient penetration of light sources. This study assessed the anticancer effects of a novel photosensitizer 5-(4-amino-phenyl)-10,15,20-triphenylporphyrin with diethylene-triaminopentaacetic acid (ATPP-DTPA)-mediated PDT (hereinafter referred to as ATPP-PDT) under the irradiation of a 450-nm blue laser on colorectal cancer (CRC) and .
METHODS
After 450-nm blue laser-mediated ATPP-PDT and the traditional photosensitizer 5-aminolevulinic acid (5-ALA)-PDT treatment, cell viability was detected through Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Reactive oxygen species (ROS) generation was quantified by flow cytometry and fluorescence microscopy. Western blotting and transcriptome RNA sequencing and functional experiments were used to evaluate cell apoptosis and its potential mechanism. Anti-tumor experiment was performed in nude mice with subcutaneous tumors.
RESULTS
ATPP-DTPA had a marvelous absorption in the blue spectrum. Compared with 5-ALA, ATPP-DTPA could achieve significant killing effects at a lower dose. Owing to generating an excessive amount of ROS, 450-nm blue laser-mediated PDT based on ATPP-DTPA resulted in evident growth inhibition and apoptosis in CRC cells . After transcriptome RNA sequencing and functional experiments, p38 MAPK signaling pathway was confirmed to be involved in the regulation of apoptosis induced by 450-nm blue laser-mediated ATPP-PDT. Additionally, animal studies using xenograft model confirmed that ATPP-PDT had excellent anti-tumor effect and reasonable biosafety .
CONCLUSIONS
PDT mediated by 450-nm blue laser combined with ATPP-DTPA may be a novel and effective method for the treatment of CRC.
Topics: Photochemotherapy; Colorectal Neoplasms; Apoptosis; Animals; Photosensitizing Agents; Humans; Mice, Nude; Reactive Oxygen Species; Mice; Cell Line, Tumor; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Lasers; Cell Survival; Aminolevulinic Acid
PubMed: 38812322
DOI: 10.31083/j.fbl2905199 -
Frontiers in Bioscience (Landmark... Apr 2024The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and... (Review)
Review
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.
Topics: Anthraquinones; Photochemotherapy; Photosensitizing Agents; Humans; Plants
PubMed: 38812303
DOI: 10.31083/j.fbl2905168 -
Bioorganic & Medicinal Chemistry Letters Sep 2024The efficacy of molecular-targeted photodynamic therapy (MT-PDT) targeting carbonic anhydrase (CA) IX, a cancer-specific molecule, was demonstrated. CA ligand-directed...
The efficacy of molecular-targeted photodynamic therapy (MT-PDT) targeting carbonic anhydrase (CA) IX, a cancer-specific molecule, was demonstrated. CA ligand-directed photosensitizers 1-3 were evaluated for their ability to deactivate CAIX protein in cells. Compounds 2 and 3 selectively deactivated CAIX protein under 540 nm light without affecting internal standard proteins. Mechanistic studies revealed that compound 3 not only induced CAIX-selective light inactivation via singlet oxygen but also induced cell membrane damage, resulting in an anti-tumor effect. In vivo studies of CAIX-targeting MT-PDT revealed that treatment with compound 3 followed by light irradiation exhibited remarkable anti-tumor activity, leading to tumor degeneration and necrosis.
Topics: Photochemotherapy; Carbonic Anhydrase IX; Humans; Photosensitizing Agents; Animals; Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Molecular Structure; Cell Line, Tumor; Mice; Structure-Activity Relationship; Antigens, Neoplasm; Drug Screening Assays, Antitumor; Dose-Response Relationship, Drug
PubMed: 38810709
DOI: 10.1016/j.bmcl.2024.129821 -
Colloids and Surfaces. B, Biointerfaces Aug 2024Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its...
Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.
Topics: Enterococcus faecalis; Photochemotherapy; Anti-Bacterial Agents; Biofilms; Octoxynol; Reactive Oxygen Species; Tolonium Chloride; Humans; Microbial Sensitivity Tests; Dental Pulp Cavity; Photosensitizing Agents
PubMed: 38810466
DOI: 10.1016/j.colsurfb.2024.113978 -
Biomedicine & Pharmacotherapy =... Jul 2024Lung cancer is one of the common forms of cancer that affects both men and women and is regarded as the leading cause of cancer related deaths. It is characterized by...
Lung cancer is one of the common forms of cancer that affects both men and women and is regarded as the leading cause of cancer related deaths. It is characterized by unregulated cell division of altered cells within the lung tissues. Green nanotechnology is a promising therapeutic option that is adopted in cancer research. Dicoma anomala (D. anomala) is one of the commonly used African medicinal plant in the treatment of different medical conditions including cancer. In the present study, silver nanoparticles (AgNPs) were synthesized using D. anomala MeOH root extract. We evaluated the anticancer efficacy of the synthesized AgNPs as an individual treatment as well as in combination with pheophorbide a (PPBa) mediated photodynamic therapy (PDT) in vitro. UV-VIS spectroscopy, high-resolution transmission electron microscopy (HR-TEM), Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) was used to confirm the formation of D.A AgNPs. Post 24 h treatment, A549 cells were evaluated for ATP proliferation, morphological changes supported by LIVE/DEAD assay, and caspase activities. All experiments were repeated four times (n=4), with findings being analysed using SPSS statistical software version 27 set at 0.95 confidence interval. The results from the present study revealed a dose-dependent decrease in cell proliferation in both individual and combination therapy of PPBa mediated PDT and D.A AgNPs on A549 lung cancer cells with significant morphological changes. Additionally, LIVE/DEAD assay displayed a significant increase in the number of dead cell population in individual treatments (i.e., IC's treated A549 cells) as well as in combination therapy. In conclusion, the findings from this study demonstrated the anticancer efficacy of green synthesized AgNPs as a mono-therapeutic drug as well as in combination with a chlorophyll derivative PPBa in PDT. Taken together, the findings highlight the therapeutic potential of green nanotechnology in medicine.
Topics: Humans; Silver; Metal Nanoparticles; A549 Cells; Lung Neoplasms; Plant Extracts; Apoptosis; Green Chemistry Technology; Chlorophyll; Photochemotherapy; Cell Proliferation; Cell Survival
PubMed: 38810403
DOI: 10.1016/j.biopha.2024.116845 -
ACS Nano Jun 2024Nanomaterials with unique structures and components play a crucial role in nanomedicine. In this study, we discovered that the inhomogeneous AuS constructed by cation...
Nanomaterials with unique structures and components play a crucial role in nanomedicine. In this study, we discovered that the inhomogeneous AuS constructed by cation exchange and acid etching could dissipate energy in different forms after absorbing multichromatic light, which could be used to achieve the integrated diagnosis and treatment of tumors, respectively. Folic acid modified AuS ringed nanoparticles (FA-AuS RNs) with an assembly-like structure were demonstrated to result in better PA imaging performance and generate more reactive oxygen species (O2·, ·OH, and O) than folic acid modified AuS triangular nanoparticles (FA-AuS TNs). Finite element analyses determined the reason for the high absorbance properties and synergistic enhancement of plasma resonance in the assembly-like structure of AuS RNs. Both FA-AuS nanostructures were modified with folic acid and injected into 4T1 tumor-bearing mice via the tail vein. The best PA imaging contrast was obtained under 700 nm laser illumination, and the most effective PDT antitumor activity was achieved under 1064 nm laser illumination. The PA average of the tumor in the FA-AuS RN group was approximately 2 times higher than that of the FA-AuS TN group at 24 h of injection. The PA imaging results of intratumorally injected FA-AuS RNs proved that they were still able to show better PA signal enhancement at 24 h postinjection. Our study demonstrates that FA-AuS nanomaterials with unique structures and special properties can be reliably produced using strictly controlled chemical synthesis. It further provides a strategy for the construction of highly sensitive PA imaging platforms and efficient PDT antitumor agents that exploit wavelength-dependent energy dissipation mechanisms.
Topics: Animals; Photochemotherapy; Gold; Mice; Photoacoustic Techniques; Folic Acid; Mice, Inbred BALB C; Female; Photosensitizing Agents; Cell Line, Tumor; Reactive Oxygen Species; Antineoplastic Agents; Metal Nanoparticles
PubMed: 38808608
DOI: 10.1021/acsnano.3c13085