{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yi M"],"funding":["National Cancer Institute","NCI NIH HHS","Division of Materials Research","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["13055-13059"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9339482"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["144(29)"],"pubmed_abstract":["Bone metastasis remains a challenge in cancer treatment. Here we show enzymatic responsive rigid-rod aromatics acting as the substrates of \"undruggable\" phosphatases to kill cancer cells in a mimetic bone microenvironment. By phosphorylation and conjugating nitrobenzoxadiazole (NBD) to hydroxybiphenylcarboxylate (BP), we obtained pBP-NBD (<b>1P</b>) as a substrate of both acid and alkaline phosphatases. <b>1P</b> effectively kills both metastatic castration-resistant prostate cancer cells (mCRPCs) and osteoblast mimic cells in their coculture. <b>1P</b> enters Saos2 almost instantly to target the endoplasmic reticulum (ER) of the cells. Co-culturing with Saos2 cells boosts the cellular uptake of <b>1P</b> by mCRPCs. Cryo-EM reveals the nanotube structures of both <b>1P</b> (2.4 Å resolution, pH 5.6) and <b>1</b> (2.2 Å resolution, pH 7.4). The helical packing of both nanotubes is identical, held together by strong pi-stacking interactions. Besides reporting the atomistic structure of nanotubes formed by the assembly of rigid-rod aromatics, this work expands the pool of molecules for designing EISA substrates that selectively target TME."],"journal":["Journal of the American Chemical Society"],"pubmed_title":["Enzyme Responsive Rigid-Rod Aromatics Target \"Undruggable\" Phosphatases to Kill Cancer Cells in a Mimetic Bone Microenvironment."],"pmcid":["PMC9339482"],"funding_grant_id":["GM122510","R00 GM138756","K99GM138756","R35 GM122510","K99 GM138756","CA252364","DMR-2011846","R21 CA252364","CA142746","R01 CA142746"],"pubmed_authors":["Hsieh JT","Tan W","Xu B","Yi M","Egelman EH","Wang F"],"additional_accession":[]},"is_claimable":false,"name":"Enzyme Responsive Rigid-Rod Aromatics Target \"Undruggable\" Phosphatases to Kill Cancer Cells in a Mimetic Bone Microenvironment.","description":"Bone metastasis remains a challenge in cancer treatment. Here we show enzymatic responsive rigid-rod aromatics acting as the substrates of \"undruggable\" phosphatases to kill cancer cells in a mimetic bone microenvironment. By phosphorylation and conjugating nitrobenzoxadiazole (NBD) to hydroxybiphenylcarboxylate (BP), we obtained pBP-NBD (<b>1P</b>) as a substrate of both acid and alkaline phosphatases. <b>1P</b> effectively kills both metastatic castration-resistant prostate cancer cells (mCRPCs) and osteoblast mimic cells in their coculture. <b>1P</b> enters Saos2 almost instantly to target the endoplasmic reticulum (ER) of the cells. Co-culturing with Saos2 cells boosts the cellular uptake of <b>1P</b> by mCRPCs. Cryo-EM reveals the nanotube structures of both <b>1P</b> (2.4 Å resolution, pH 5.6) and <b>1</b> (2.2 Å resolution, pH 7.4). The helical packing of both nanotubes is identical, held together by strong pi-stacking interactions. Besides reporting the atomistic structure of nanotubes formed by the assembly of rigid-rod aromatics, this work expands the pool of molecules for designing EISA substrates that selectively target TME.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2025-04-04T20:06:52.488Z","creation":"2025-04-04T20:06:52.488Z"},"accession":"S-EPMC9339482","cross_references":{"pubmed":["35849554"],"doi":["10.1021/jacs.2c05491"]}}