Heavy Atom‐Free, Mitochondria‐Targeted, and Activatable Photosensitizers for Photodynamic Therapy with Real‐Time In‐Situ Therapeutic Monitoring

Abstract

Based on spin‐orbit charge transfer intersystem crossing mechanism, two heavy‐atom‐free photosensitizers (PSs) BDP1/BDP2 with absorption maxima at 506 nm/660 nm were constructed for photodynamic therapy (PDT). The long triplet state lifetimes and large singlet oxygen quantum yields, coupled with the mitochondria‐targeted feature, made them highly phototoxic toward cancer cells. Moreover, the PDT‐promoted cell apoptosis could be monitored by an obvious fluorescence off‐on response of the two PSs due to the concomitant activation of extensive mitophagy, thus facilitating timely therapeutic feedback to avoid under‐ or over‐treatment. Importantly, such design allows the activatable PSs Glu‐BDP1/Glu‐BDP2 to be fabricated by attaching γ‐glutamyl, a substrate of γ‐glutamyltranspeptidase, to the alkoxyaniline unit of BDP1/BDP2, and their ability in either selectively killing cancer cells over normal cells or in ablating implanted tumour without damage to healthy tissue was demonstrated.

Insights into the organic semiconducting photosensitizers for hypoxia-tolerant type I photodynamic therapy

“…A general PDT procedure involves the photochemical reaction of a PS and endogenous O2 to generate highly cytotoxic reactive oxygen species (ROS) that cause cell death, vascular damage, and immune response (Fig. 1) [18][19][20][21]. It means that PDT can eradicate not only the local primary tumor but also the recurrent or metastatic solid tumors by inducing inflammation or immunogenic cell death (ICD), which meets the requirements of long-time therapy of tumors [22][23][24][25][26].…”

Nanoparticle-Based Artificial Mitochondrial DNA Transcription Regulator: MitoScript

“…MitoScript ’s unique properties allow it to be soluble in water and a range of buffers, and it can be delivered to targeted cellular suborganelles (e.g., mitochondria) in a biocompatible or nonviral way. Additionally, because of the zwitterionic nature of its surface ligands (anionic GSH linkers, cationic MPPs, and PIPs), MitoScript can be effectively uptaken by cells, which further leads to the targeting of the mitochondria. − In parallel, the endogenous fluorescence generated by quantum confinement at the nanoscale sizes of gold nanoclusters can be applied to visualize cellular uptake and mitochondria targeting. − Most crucially, MitoScript was effectively as well as selectively delivered to mitochondria and regulated mtDNA transcription. The NADH-ubiquinone oxidoreductase chain six protein (ND6) is a crucial subunit of NADH dehydrogenase in the electron transport chain and is transcribed by the light chain of circular mtDNA (Figure b). , When the mtDNA binding domain was specifically engineered for binding to the minor groove of the light chain TFAM binding sites, we selectively suppressed ND6 genes in HeLa cells.…”

Near-Infrared Photooxygenation Theranostics Used for the Specific Mapping and Modulating of Amyloid-β Aggregation

“…The abnormal folding of proteins is often toxic and associated with many diseases . β-Amyloid is one of the main pathological mechanisms of Alzheimer’s disease (AD), which is caused by the incorrect aggregation of Aβ monomers to form oligomers and aggregates that induce neurotoxicity. − Current research strategies used for the treatment of AD based on Aβ protein are mainly focused on interfering with the abnormal assembly of Aβ or decomposing preformed fibrils. − At present, photodynamic therapy (PDT) has been explored as a promising method − with singlet oxygen ( 1 O 2 ) being the main substance used for the photooxygenation of Aβ. , The mechanism of its generation and its application in in vivo and in vitro AD models have been reported in the present study. , …”