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Pyrazole appended quinoline-BODIPY based arene ruthenium complexes: their anticancer activity and potential applications in cellular imaging
摘要： Synthesis of an entirely new series of arene ruthenium complexes [Ru(η6-C6H6)(L1)Cl]PF6, (1), [Ru(η6-C10H14)(L1)Cl]PF6 (2), [Ru(η6-C6H6)(L2)Cl]PF6 (3) and [Ru(η6-C10H14)(L2)Cl]PF6 (4) involving 5-[2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L1) and 5-[6-methoxy-2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L2) was described. The ligands and complexes were thoroughly characterized by various physicochemical techniques and the structures of L1, 1 and 4 were determined by X-ray single crystal analyses. Photo-/ and electrochemical property, DNA binding, cytotoxicity, cellular uptake and apoptotic studies on 1–4 were performed by various methods, while singlet oxygen-mediated cytotoxicity via photo-irradiation by visible light was supported by 1,3-diphenylisobenzofuran titration studies. Binding of the complexes in the minor groove of CT-DNA via van der Waals forces and electrostatic interactions was affirmed by molecular docking studies. In vitro antiproliferative activity and photocytotoxicity of 1–4 were examined against the human cervical cancer cell line (HeLa) which clearly showed that these are extremely photocytotoxic under visible light (400–700 nm, 10 J cm?2; IC50 49.15, 1; 25.18, 2; 15.85, 3; 12.87, 4), less toxic in the dark (IC50 > 100 μM) and preferentially accumulate in the lysosome of the HeLa cells. Further, these complexes behave as a potential theranostic agent and their ability to kill cancer cells under visible light lies in the order 4 > 3 > 2 > 1.
关键词： singlet oxygen,arene ruthenium complexes,DNA binding,cellular imaging,BODIPY,photodynamic therapy,anticancer activity
更新于2025-09-19 17:15:36
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Targeted and synergic glioblastoma treatment: multifunctional nanoparticles delivering verteporfin as adjuvant therapy for temozolomide chemotherapy
摘要： Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low Temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies: (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles (m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in Pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and co-encapsulate multiple cargoes under optimized conditions. Overall, the present study conducts a rational m-NP design, characterization, and optimizes the formulation conditions. Confocal microscopy studies on T98-G, U87-MG, and U343 glioblastoma cells and on NIH-3T3 normal fibroblast cells show that the m-NPs and the encapsulated drugs are selectively taken up by tumor cells presenting a broad intracellular distribution. The formulations display no toxicity in the absence of light and are not toxic to healthy cells, but they exert a robust synergic action in cancer cells in the case of concomitant PDT/TMZ treatment, especially at low TMZ concentrations and higher light doses, as demonstrated by nonlinear dose–effect curves based on Chou-Talalay method. The results evidenced different mechanisms of action related to the disjoint cell cycle phases at the optimal PDT/TMZ ratio. This effect favors synergism between the PDT and the chemotherapy with TMZ, enhances the antiproliferative effect, and overcomes cross-resistance mechanisms. These results point out that m-NP-based PDT adjuvant therapy is a promising strategy to improve TMZ-based glioblastoma multiforme treatments.
关键词： Verteporfin,Temozolomide,Photodynamic therapy,Nanotechnology,Theranostic
更新于2025-09-19 17:15:36
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Synthesis and aggregation of a porphyrin cored hyperbranched polyglycidol and its application as a macromolecular photosensitizer for photodynamic therapy
摘要： Macromolecules are potentially useful delivery systems for cancer drugs as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protecting and solubilizing toxic and hydrophobic drug moieties. Overall these properties and abilities can result in an enhanced therapeutic effect. Photodynamic therapy (PDT) combines the use of oxygen and a photosensitizer (PS), that become toxic upon light-irradiation. We proposed that a PS encapsulated within a water-soluble macromolecule could exploit the EPR effect and safely and selectively deliver the PS to a tumor. In this paper, we describe the synthesis of a porphyrin cored hyperbranched polymer that aggregated into larger micellar structures. DLS and TEM indicated that these aggregated structures had diameters of 45 nm and 20 nm for the solvated and non-solvated species respectively. The porphyrin cored HBP (PC-HBP), along with the non-encapsulated porphyrin (THPP), were screened against EJ bladder carcinoma cells in the dark and light. Both THPP and PC-HBP displayed good toxicity in the light, with LD50 concentrations of 0.5 μM and 1.7 μM respectively. However, in the dark, the non-incorporated porphyrin (THPP) displayed significant toxicity, generating an LD50 of 4 μM. On the other hand, no dark toxicity was observed for the polymer system (PC-HBP) at concentrations of 100 μM or less. As such, incorporation within the large polymer aggregate serves to eliminate dark toxicity, whilst maintaining excellent toxicity when irradiated.
关键词： self-assembly.,hyperbranched polymers,drug delivery,Photodynamic therapy
更新于2025-09-19 17:15:36
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An Oxygen Self-sufficient Fluorinated Nanoplatform for Relieved Tumor Hypoxia and Enhanced Photodynamic Therapy of Cancers
摘要： The efficacy of photodynamic therapy (PDT) in the solid tumor is hampered by many challenges, including its oxygen self-consuming nature, insufficient oxygen levels within the hypoxic tumor microenvironment, and limited penetration of photosensitizers within tumors. Herein, we develop the IR780@O2-SFNs/iRGD as an oxygen self-sufficient and tumor-penetrating nanoplatform, which consists of IR780 loaded pH-sensitive fluorocarbon functionalized nanoparticles (SFNs) and iRGD as a tumor targeting peptide that can penetrate deeper within the tumor. Because of the high oxygen affinity and outstanding permeability of the obtained nanoplatform, oxygen and IR780 which are encapsulated in the same core can play their roles to the utmost, resulting in remarkably accelerated singlet oxygen production, as demonstrated in vitro by the 3D multicellular spheroids and in vivo by tumor tissues. More interestingly, a single-dose intravenous administration of IR780@O2-SFNs/iRGD into mice bearing orthotopic breast cancer could selectively accumulate at the tumor site, highly alleviate the tumor hypoxia, significantly inhibit the primary tumor growth and reduce the lung and liver metastasis, enabling the improved photodynamic therapeutic performance. Thus, this work paves an effective way to improve PDT efficacy through increasing tumor oxygenation and selective delivery of photosensitizers to the deep and hypoxic tumor.
关键词： oxygen self-sufficient,tumor penetration,tumor oxygenation,photodynamic therapy,orthotopic breast cancer
更新于2025-09-19 17:15:36
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Post-Synthetic Ligand Exchange of Metal Organic Framework for Photodynamic Therapy
摘要： Attributed to the large pore size and excellent stability, the metal organic framework (MOF) NU-1000, which is formed by the coordination of Zr cluster and 1,3,6,8-tetrakis(p-benzoicacid)pyrene (H4TBAPy) ligand, has been widely studied in the catalysis research field, however, only a few reports about the biomedical application of NU-1000 could be found in the open literature. In this study, a functional ligand, tetrakis(4-carboxyphenyl)porphyrin (TCPP) was introduced into NU-1000 via post-synthetic ligand exchange method, and the resultant mixed ligand MOF possesses excellent photodynamic effect. Finally, in vitro and in vivo assessment about the antitumor efficacy was investigated for the first time. It demonstrates the feasibility of TCPP substituted NU-1000 to be used for photodynamic therapy, and also provides an alternative approach to enrich the function of MOF for various applications via post-synthetic method.
关键词： Metal Organic Frameworks,ligand exchange,NU-1000,photodynamic therapy,post-synthetic modification
更新于2025-09-19 17:15:36
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Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration
摘要： Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated. Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285). Conclusion: The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.
关键词： pigment epithelial detachment,photodynamic therapy,phenotypic and genotypic factors,greatest linear dimension,high temperature requirement A-1,age-related macular degeneration
更新于2025-09-19 17:15:36
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Inhibition of Autophagy with Chloroquine Enhanced Sinoporphyrin Sodium Mediated Photodynamic Therapy-induced Apoptosis in Human Colorectal Cancer Cells
摘要： To evaluate the antitumor effect of sinoporphyrin sodium mediated photodynamic therapy (DVDMS-PDT) against human colorectal cancer (CRC) and to investigate the role of autophagy in its effect. Shrunken cells, condensed nuclei and increased levels of cleaved caspase-3 and Bax were observed in DVDMS-PDT treated HCT116 cells, reminiscent of apoptosis. DVDMS-PDT showed better antitumor efficiency in HCT116 cells than Photofrin mediated photodynamic therapy (PF-PDT) both in vitro and in vivo. And DVDMS-PDT caused autophagic characteristics: double membrane autophagosome structures and changes in autophagy-related protein expression (ATG7, P62, Bcl-2 and LC3-Ⅱ). In addition, inhibition of autophagy by chloroquine (CQ) promoted apoptosis, suggesting a possible protective role of autophagy in DVDMS-PDT-treated HCT116 cells, which was proved by flow cytometry and western blotting. The results of xenograft mouse model showed markedly increased apoptosis and significantly reduced tumor size in DVDMS-PDT treated group than Control, and DVDMS-PDT exhibited better antitumor efficiency than PF-PDT. Further, no visible tumor was observed in the CQ+DVDMS-PDT group at the end of the xenograft mouse experiment, which confirmed the hypothesis that autophagy was protective to DVDMS-PDT treated HCT116 cells. Our findings suggest that DVDMS is a promising photosensitizer and the combined use of autophagy inhibitor can remarkably enhance the DVDMS-PDT mediated anti-cancer efficiency in HCT116 cells both in vitro and in vivo.
关键词： autophagy,apoptosis,photodynamic therapy,chloroquine,sinoporphyrin sodium,colorectal cancer
更新于2025-09-19 17:15:36
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Statement of the BVA, the DOG, and the RG on treatment of choroidal neovascularization in diseases other than neovascular age-related macular degeneration; Stellungnahme des BVA, der DOG und der RG zur Therapie chorioidaler Neovaskularisationen bei anderen Erkrankungen als der neovaskul?ren altersabh?ngigen Makuladegeneration (Englische Version);
摘要： Choroidal neovascularizations (CNV) occur not only in age-related macular degeneration (AMD), but also in numerous other macular and retinal disorders of varying etiology and, if left untreated, can cause irreversible visual loss. The diagnosis of CNV as well as the indication for treatment should be made in the same way as in neovascular AMD: On initial diagnosis: best-corrected visual acuity, fundus examination, optical coherence tomography (OCT), and fluorescein angiography. At follow-up: best-correct visual acuity, fundus examination, OCT, and, depending on findings, fluorescein angiography. Active CNV should be treated with intravitreal operative medication (IVOM) using vascular endothelial growth factor (VEGF) inhibitors if patients have visual acuity of at least 0.05 or if there is sufficient reason to assume that visual acuity could increase to over 0.05 under treatment. Underlying disorders can include, e.g., high myopia, angioid streaks, central serous chorioretinopathy, active and inactive uveitis of varying etiology, including retinochoroiditis, chorioretinitis, and choroiditis, eye injuries, retinal dystrophies, e.g., best disease and pattern dystrophies, idiopathic CNV, subretinal masses (osteomas, hamartomas, nevi). If CNV is not present as a complication in the above-mentioned disorders, IVOM with VEGF inhibitors should not be performed. Ranibizumab and aflibercept are approved in Germany for the treatment of CNV secondary to pathologic myopia. Ranibizumab has been approved in Germany since 12/2016 for the treatment of CNV in disorders other than neovascular AMD and pathologic myopia irrespective of the underlying disease. The other VEGF inhibitors, aflibercept and bevacizumab, can be used off-label. Due to its overall significantly poorer treatment results, photodynamic therapy (PDT) should only be used in exceptional cases and extrafoveal localization. After one initial intravitreal administration of VEGF inhibitors, further CNV activity should be monitored monthly for the first 6 months (see point 2). In the case of persisting or recurrent activity, repeated IVOM should be performed. Depending on disease course, the follow-up interval might be extended 6 months after the last IVOM. In individual justified cases (e.g., patients requiring frequent re-injections), a different treatment regimen (e.g., treat and extend) can be considered in the further course. If visual acuity drops below 0.05 on anti-VEGF treatment, or no further positive treatment outcome is expected (e.g., in the presence of atrophy and/or fibrosis), treatment should be discontinued, unless there is a clear possibility that visual acuity could increase again to over 0.05 under treatment. If no improvement is seen under therapy with a certain VEGF inhibitor, or if deterioration occurs, one can consider switching to an alternative VEGF inhibitor.
关键词： Choroidal neovascularization,Myopia,Retinal dystrophies,Ranibizumab,VEGF inhibitors,Uveitis,Idiopathic CNV,Central serous chorioretinopathy,Angioid streaks,Photodynamic therapy,Subretinal tumors,Aflibercept,Bevacizumab,Eye injuries
更新于2025-09-19 17:15:36
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P-glycoprotein targeted photodynamic therapy of chemoresistant tumors using recombinant Fab fragment conjugates
摘要： P-glycoprotein (Pgp) has been considered as a major cause of cancer multidrug resistance; however, clinical solutions to overcome this drug resistance do not exist despite the tremendous endeavors. The lack of cancer specificity is a main reason for clinical failure of conventional approaches. Targeted photodynamic therapy (PDT) is highly cancer specific by combining antibody targeting and locoregional light irradiation. We aimed to develop Pgp-targeted PDT using antibody–photosensitizer conjugates made of a recombinant Fab fragment. We prepared the photosensitizer conjugates by expressing a recombinant Fab fragment and specifically linking IR700-maleimide at the C-terminal of the Fab heavy chain. In vitro studies showed that the Fab conjugates specifically bind to Pgp. Their phototoxicity was comparable to full antibody conjugates when assayed with conventional 2-D cell culture, but they outperformed the full antibody conjugates in a 3-D tumor spheroid model. In a mouse xenograft model of chemoresistant tumors, Fab conjugates showed Pgp specific delivery to chemoresistant tumors. Upon irradiation with near-infrared light, they caused rapid tumor shrinkage and significantly prolonged the survival of tumor-bearing mice. Compared to the full antibody conjugates, Fab conjugates took a shorter time to reach peak tumor levels and achieved a more homogeneous tumor distribution. This allows light irradiation to be initiated at a shorter time interval after the conjugate injection, and thus may facilitate clinical translation. We conclude that our targeted PDT approach provides a highly cancer-specific approach to combat chemoresistant tumors, and that the conjugates made of recombinant antibody fragments are superior to full antibody conjugates for targeted PDT.
关键词： chemoresistance,P-glycoprotein,recombinant Fab fragment,photodynamic therapy,antibody conjugates
更新于2025-09-19 17:15:36
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Investigation of copper-cysteamine nanoparticles as a new photosensitizer for anti-hepatocellular carcinoma
摘要： Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. HCC is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected. However, there is no complete effective (ideal) treatment for liver cancer yet, and the new methods are expected to be discovered. Herein, for the first time, we report the anti-HCC effects of copper-cysteamine nanoparticles (Cu-Cy NPs), a new type of photosensitizers. An in vitro 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that Cu-Cy NPs could significantly reduce the activity of HepG2 cells at a very low dose after a short time of ultraviolet radiation. In addition, we found that cell death was induced by Cu-Cy NPs, which is associated with cellular apoptosis. This implied that apoptosis might be the main mechanism of the Cu-Cy’s anti-HCC activity. Furthermore, we found that Cu-Cy NPs obviously inhibited the tumor growth in vivo. More interestingly, we found that the soluble Cu-Cy NPs were able to enter exosomes which were secreted by tumor cells, and exosomes could be used to deliver Cu-Cy NPs to target tumor cells. All these observations suggest that Cu-Cy NPs have a good potential for cancer treatment.
关键词： copper-cysteamine,Hepatocellular carcinoma,nanoparticles,photosensitizer,photodynamic therapy
更新于2025-09-19 17:15:36