Tuning the hydrophobicity of pyridinium-based probes to realize the mitochondria-targeted photodynamic therapy and mitophagy tracking

Zhang, Yuyang; Wang, Lianke; Rao, Qingpeng; Bu, Yingcui; Xu, Tianren; Zhu, Xiaojiao; Zhang, Jie; Tian, Yupeng; Zhou, Hongping

doi:10.1016/j.snb.2020.128460

Cited by 31 publications

(16 citation statements)

References 39 publications

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“…In another study, Zhou et al reported a series of cationic AIEgens ( 427 ) based on triphenylamine–pyridinium conjugates for mitophagy tracking and mitochondria-targeted PDT (Figure ). , Their mitochondria targeting ability could be gradually enhanced by lengthening of alkyl chains on the pyridinium moiety. In addition, Chen et al synthesized two cationic AIEgens based on the tetraphenylethylene–thiophene–pyridinium conjugate with PDT for bacterial inactivation and cancer cell ablation (Figure ).…”

Section: Enhanced Photodynamic Therapy By Organelle-targeted Photosen...mentioning

confidence: 99%

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

et al. 2021

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This review presents a robust strategy to design photosensitizers (PSs) for various species. Photodynamic therapy (PDT) is a photochemical-based treatment approach that involves the use of light combined with a light-activated chemical, referred to as a PS. Attractively, PDT is one of the alternatives to conventional cancer treatment due to its noninvasive nature, high cure rates, and low side effects. PSs play an important factor in photoinduced reactive oxygen species (ROS) generation. Although the concept of photosensitizer-based photodynamic therapy has been widely adopted for clinical trials and bioimaging, until now, to our surprise, there has been no relevant review article on rational designs of organic PSs for PDT. Furthermore, most of published review articles in PDT focused on nanomaterials and nanotechnology based on traditional PSs. Therefore, this review aimed at reporting recent strategies to develop innovative organic photosensitizers for enhanced photodynamic therapy, with each example described in detail instead of providing only a general overview, as is typically done in previous reviews of PDT, to provide intuitive, vivid, and specific insights to the readers.

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Section: Enhanced Photodynamic Therapy By Organelle-targeted Photosen...mentioning

confidence: 99%

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

et al. 2021

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“…A series of PSs were designed and synthesized based on the excellent phototoxicity and biological applications of AIE (Figure ). − These PSs are endowed with the ability to target mitochondria by introducing a quaternary ammonium salt or a pyridinium, thereby enhancing the PDT effects. ,,, …”

Section: Mitochondria-targeted Pssmentioning

confidence: 99%

Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy

Wang

Yoon

2021

ACS Appl. Mater. Interfaces

157

140

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Subcellular organelles are the cornerstones of cells, and destroying them will cause cell dysfunction and even death. Therefore, realizing precise organelle targeting of photosensitizers (PSs) can help reduce PS dosage, minimize side effects, avoid drug resistance, and enhance therapeutic efficacy in photodynamic therapy (PDT). Organelle-targeted PSs provide a new paradigm for the construction of the next generation of PSs and may provide implementable strategies for future precision medicine. In this Review, the recent targeting strategies of different organelles and the corresponding design principles of molecular and nanostructured PSs are summarized and discussed. The current challenges and opportunities in organelle-targeted PDT are also presented.

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“…The characteristic, distinct sizes of the nuclei of astrocytes and microglia were used to distinguish the glial types during quantification of the florescence intensity of astrocytes and microglia. The ratio of aggregated to monomer JC-10 (590 nm/525 nm) was calculated using MetaMorph software 7.1 as previously described [46].…”

Section: Measurement Of Mitochondria Membrane Potentialmentioning

confidence: 99%

Reduced mitochondria membrane potential and lysosomal acidification are associated with decreased oligomeric Aβ degradation induced by hyperglycemia: A study of mixed glia cultures

et al. 2022

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Diabetes is a risk factor for Alzheimer’s disease (AD), a chronic neurodegenerative disease. We and others have shown prediabetes, including hyperglycemia and obesity induced by high fat and high sucrose diets, is associated with exacerbated amyloid beta (Aβ) accumulation and cognitive impairment in AD transgenic mice. However, whether hyperglycemia reduce glial clearance of oligomeric amyloid-β (oAβ), the most neurotoxic Aβ aggregate, remains unclear. Mixed glial cultures simulating the coexistence of astrocytes and microglia in the neural microenvironment were established to investigate glial clearance of oAβ under normoglycemia and chronic hyperglycemia. Ramified microglia and low IL-1β release were observed in mixed glia cultures. In contrast, amoeboid-like microglia and higher IL-1β release were observed in primary microglia cultures. APPswe/PS1dE9 transgenic mice are a commonly used AD mouse model. Microglia close to senile plaques in APPswe/PS1dE9 transgenic mice exposed to normoglycemia or chronic hyperglycemia exhibited an amoeboid-like morphology; other microglia were ramified. Therefore, mixed glia cultures reproduce the in vivo ramified microglial morphology. To investigate the impact of sustained high-glucose conditions on glial oAβ clearance, mixed glia were cultured in media containing 5.5 mM glucose (normal glucose, NG) or 25 mM glucose (high glucose, HG) for 16 days. Compared to NG, HG reduced the steady-state level of oAβ puncta internalized by microglia and astrocytes and decreased oAβ degradation kinetics. Furthermore, the lysosomal acidification and lysosomal hydrolysis activity of microglia and astrocytes were lower in HG with and without oAβ treatment than NG. Moreover, HG reduced mitochondrial membrane potential and ATP levels in mixed glia, which can lead to reduced lysosomal function. Overall, continuous high glucose reduces microglial and astrocytic ATP production and lysosome activity which may lead to decreased glial oAβ degradation. Our study reveals diabetes-induced hyperglycemia hinders glial oAβ clearance and contributes to oAβ accumulation in AD pathogenesis.

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Tuning the hydrophobicity of pyridinium-based probes to realize the mitochondria-targeted photodynamic therapy and mitophagy tracking

Cited by 31 publications

References 39 publications

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

Recent Strategies to Develop Innovative Photosensitizers for Enhanced Photodynamic Therapy

Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy

Reduced mitochondria membrane potential and lysosomal acidification are associated with decreased oligomeric Aβ degradation induced by hyperglycemia: A study of mixed glia cultures

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