Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer

Zhang, Shaojuan; Yang, Ling; Ling, Xiaoxi; Shao, Pengfei; Wang, Xiaolei; Edwards, Wilson B.; Bai, Mingfeng

doi:10.1016/j.actbio.2015.09.033

Cited by 66 publications

(53 citation statements)

References 46 publications

(52 reference statements)

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“…42 High levels of ROS can disrupt the mitochondrial permeability transition pore and destroy the integrity of the mitochondrial membrane, resulting in immediate dissipation of mitochondrial transmembrane potential and osmotic swelling of the mitochondrial matrix. 43,44 Once …”

Section: Discussionmentioning

confidence: 99%

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

Jiang¹,

Zhu²,

He³

et al. 2016

IJN

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Section: Discussionmentioning

confidence: 99%

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

Jiang¹,

Zhu²,

He³

et al. 2016

IJN

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“…TSPO-targeted PS, IR700DX-6T [32], and CB 2 R-targeted PS, IR700DX-mbc94 [31] (Figure 1), which share the same PS (IR700DX), were synthesized using previously reported methods. We first evaluated ROS production from IR700DX-mbc94 and IR700DX-6T upon light irradiation using singlet oxygen sensor green (SOSG).…”

Section: Resultsmentioning

confidence: 99%

“…Compared with other types of breast cancer, those with triple negative breast cancer (TNBC) have a poorer survival rate. Therefore, treatment of TNBC represents a great clinical challenge; (2) In our recent study, we found that TSPO-targeted PDT was effective in treating MDA-MB-231 cells and tumors in a target-specific manner [32]. In this study, we were interested in investigating whether adding CB 2 R-PDT to TSPO-PDT would further improve the therapeutic effect; (3) Although MDA-MB-231 cells express CB 2 R at a relatively low level, the binding affinity of IR700DX-mbc94 is much higher than IR700DX-6T (K D = 42 nM for IR700DX-mbc94 vs 1.9 μM for IR700DX-6T) [31, 32].…”

Section: Discussionmentioning

confidence: 99%

“…In our recent studies, we developed two cancer-specific PDT PSs, IR700DX-mbc94 and IR700DX-6T, which target cannabinoid CB2 receptor (CB 2 R) and translocator protein (TSPO), respectively [30–32]. CB 2 R belongs to the G protein–coupled receptors (GPCRs, plasma membrane receptors) family and is predominantly a peripheral receptor abundantly expressed by immune cells [33, 34].…”

Section: Introductionmentioning

confidence: 99%

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Multilayer photodynamic therapy for highly effective and safe cancer treatment

et al. 2017

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Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.

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“…Photodynamic therapy utilizing an 18 kDa mitochondrial translocator protein target by administering IR700DX-6T induced apoptosis in MDA-MB-231 breast cancer cells [13].…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Untitled

2017

IJRRT

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Significant participation of constitutive self-programming of apoptotic pathways indicates an in-built series of mechanistic pathways that protect against susceptibility patterns of evolving carcinogenesis. As such the incremental exposure pathways include dimensional re-formulation of events as wellestablished programmed schemes of network operability within the further conceptual realization of direct and indirect effects on cell viability once malignant transformation has taken place. Specific contexts of strict preconditioning and further stages of sustained conditions of cells such as seen in epithelial cells of breast and uterus come to operate in dominant fashion in determining cell-subset fate outcome when such cells are exposed to stress or injury. Chemotherapeutic resistance of malignant tumor cells would arise in terms of such contextual conditioning that includes in particular the genotype of the cells concerned. Mechanistic individualization of component intermediates of specific pathways is modulated in a manner that enhances such context of involvement of integral cells beyond the simple conformations of even interactive systems of effect and progression. Initial response of tumor cells to administered chemotherapeutic agents is supplemented by the development of second-stage resistance to such agents in many patients and would be indicative of adaptive low-metabolic status and non-proliferation of the tumor cells. In this setting, parameters of integration belie stratified re-organization of individual pathway mechanics and would implicate otherwise homeostatic countersystems that enhance pro-apoptosis or anti-apoptosis in response to radiation or chemotherapy of tumor cells.

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Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer

Cited by 66 publications

References 46 publications

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles

Multilayer photodynamic therapy for highly effective and safe cancer treatment

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