{"doi":"10.1021/acsami.1c22869","title":"Controlled and Selective Photo-oxidation of Amyloid-β Fibrils by Oligomeric <i>p</i> -Phenylene Ethynylenes","abstract":"Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer’s disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo-p-phenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-β (Aβ) and α-synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aβ fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aβ40, OPE oxidized only Aβ40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic β-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE’s photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.","journal":"ACS Applied Materials & Interfaces","year":2022,"id":255159,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":903403,"name":"Daniel Okoye","orcid":null,"position":1,"is_corresponding":false},{"id":330041,"name":"Florencia A. Monge","orcid":null,"position":2,"is_corresponding":false},{"id":650728,"name":"Julia Hammond","orcid":null,"position":3,"is_corresponding":false},{"id":795301,"name":"Fahimeh Maghsoodi","orcid":"0000-0001-5996-8866","position":4,"is_corresponding":false},{"id":902874,"name":"Tye D. Martin","orcid":"0000-0002-0987-0606","position":5,"is_corresponding":false},{"id":903404,"name":"Gabriella Brinkley","orcid":null,"position":6,"is_corresponding":false},{"id":663790,"name":"M. Lisa Phipps","orcid":"0000-0002-0762-8226","position":7,"is_corresponding":false},{"id":902875,"name":"Deborah G. Evans","orcid":"0000-0003-2446-6967","position":8,"is_corresponding":false},{"id":663792,"name":"Jennifer S. Martinez","orcid":"0000-0001-6737-2712","position":9,"is_corresponding":false},{"id":328141,"name":"David G. Whitten","orcid":"0000-0002-6305-9494","position":10,"is_corresponding":false},{"id":326011,"name":"Eva Y.","orcid":"0000-0001-7448-9943","position":11,"is_corresponding":false},{"id":902873,"name":"Adeline M. Fanni","orcid":"0000-0002-7240-2792","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T00:25:12.987829Z","pmid":"35344326","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}