Photodynamic Therapy: Photosensitizer Targeting and Delivery

Mróz, Paweł; Sharma, Sunil; Zhiyentayev, Timur; Huang, Ying‐Ying; Hamblin, Michael R.

doi:10.1002/9783527634057.ch48

Cited by 6 publications

(6 citation statements)

References 168 publications

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“…The precision of PDT is dependent upon selective uptake of the photosensitizer by cancer cells as well as the region where irradiation occurs. Due to suboptimal tumor targeting and uptake of current PDT drugs, considerable efforts have been made to enhance PDT drug efficacy using standard drug delivery strategies . However, in all of these approaches, the uptake of the photosensitizer into the cancer cell is a primary concern.…”

Section: Introductionmentioning

confidence: 99%

“…Due to suboptimal tumor targeting and uptake of current PDT drugs, considerable efforts have been made to enhance PDT drug efficacy using standard drug delivery strategies. 34 However, in all of these approaches, the uptake of the photosensitizer into the cancer cell is a primary concern. In order for the PDT drug to do the most damage to cancer cells, it must be able to reach intracellular organelles, especially the mitochondria; generation of ROS at the cancer cell surface is not sufficient to achieve efficient cell killing.…”

Section: ■ Introductionmentioning

confidence: 99%

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Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers

et al. 2018

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Dual action agents containing a cysteine protease inhibitor and Rubased photosensitizer for photodynamic therapy (PDT) were designed, synthesized, and validated in 2D culture and 3D functional imaging assays of triple-negative human breast cancer (TNBC). These combination agents deliver and release Rubased PDT agents to tumor cells and cause cancer cell death upon irradiation with visible light, while at the same time inactivating cathespin B (CTSB), a cysteine protease strongly associated with invasive and metastatic behavior. In total five Rubased complexes were synthesized with the formula [Ru(bpy)2(l)](O2CCF3)2 (3), where bpy = 2,2′-bipyridine and 1 = a bipyridine-based epoxysuccinyl inhibitor; [Ru(tpy)(NN)(2)](PF6)2, where tpy = terpiridine, 2 = a pyridine-based epoxysuccinyl inhibitor and NN = 2,2′-bipyridine (4); 6,6′-dimethyl-2,2′-bipyridine (5); benzo[i]dipyrido[3,2-a:2′,3′-c]phenazine (6); and 3,6-dimethylbenzo[i]-dipyrido[3,2-a:2′,3′ -c]phenazine (7). Compound 3 contains a [Ru(bpy)3]2+ fluorophore and was designed to track the subcellular localization of the conjugates, whereas compounds 4–7 were designed to undergo either photoactivated ligand dissociation and/or singlet oxygen generation. Photochemical studies confirmed that complexes 5 and 7 undergo photoactivated ligand dissociation, whereas 6 and 7 generate singlet oxygen. Inhibitors 1–7 all potently and irreversibly inhibit CTSB. Compounds 4–7 were evaluated against MDA-MB-231 TNBC and MCF-10A breast epithelial cells in 2D and 3D culture for effects on proteolysis and cell viability under dark and light conditions. Collectively, these data reveal that 4–7 potently inhibit dye-quenched (DQ) collagen degradation, whereas only compound 7 causes efficient cell death under light conditions, consistent with its ability to release a Ru(II)-based photosensitizer and to also generate 1O2.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers

et al. 2018

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“…However, the application of many PSs in clinic has been impeded by their hydrophobicity and easy aggregation in aqueous solution that greatly reduced PDT efficacy. To overcome the drawbacks and improve the PDT therapeutic efficiency, different strategies, such as loading PSs on various nanocarriers [75,[86][87][88] and the combination of PDT with other treatment modalities (e.g., chemotherapy, PTT) have been developed [75]. By utilizing some near-infrared absorption photothermal nanomaterials, such as Au and carbon nanostructures, as the carriers of PSs, high synergistic therapeutic effect has been achieved by the combination of PDT and PTT [75].…”

Section: Combination Therapy Of Cancermentioning

confidence: 99%

Two-dimensional Pd-based nanomaterials for bioapplications

et al. 2017

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“…1 H NMR (CDCl 3 ): δ = 6.39 (s, 1 H, ArH), 6.33 (s, 1 H, ArH), 6.25 (s, 1 H, ArH), 4.48 (s, 2 H, CH 2 ), 4.43 (s, 2 H, CH 2 ), 4.21 (q, J = 7.2 Hz, 2 H, CO 2 CH 2 ), 3.74 (s, 1 H, OH), 1.26 (t, J = 7.2 Hz, 3 H, CH 3 ). 13 Preparation of 12. A mixture of hydrazine hydrate (80%, 2 mL) and 11 (0.41 g, 1.10 mmol) in ethanol (2 mL) was stirred at room temperature for 30 min.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

A Dual Activatable Photosensitizer toward Targeted Photodynamic Therapy

et al. 2014

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An unsymmetrical bisferrocenyl silicon(IV) phthalocyanine has been prepared in which the disulfide and hydrazone linkers can be cleaved by dithiothreitol and acid, respectively. The separation of the ferrocenyl quenchers and the phthalocyanine core greatly enhances the fluorescence emission, singlet oxygen production, intracellular fluorescence intensity, and in vitro photocytotoxicity. The results have been compared with those for the two symmetrical analogues which contain either the disulfide or hydrazone linker and therefore can only be activated by one of these stimuli. For the dual activatable agent, the greatest enhancement can be attained under a slightly acidic environment (pH = 4.5-6.8) and in the presence of dithiothreitol (in millimolar range), which can roughly mimic the acidic and reducing environment of tumor tissues. This compound can also be activated in tumor-bearing nude mice. It exhibits an increase in fluorescence intensity in the tumor over the first 10 h after intratumoral injection and can effectively inhibit the growth of tumor upon illumination.

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Photodynamic Therapy: Photosensitizer Targeting and Delivery

Cited by 6 publications

References 168 publications

Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers

Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers

Two-dimensional Pd-based nanomaterials for bioapplications

A Dual Activatable Photosensitizer toward Targeted Photodynamic Therapy

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