{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:00:54Z","timestamp":1791176454226,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T00:00:00Z","timestamp":1352160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> The passage of drugs across the blood\u2013brain barrier (BBB) limits the efficacy of chemotherapy in brain tumours. For instance, the anticancer drug doxorubicin, which is effective against glioblastoma <jats:italic>in vitro<\/jats:italic>, has poor efficacy <jats:italic>in vivo,<\/jats:italic> because it is extruded by P\u2010glycoprotein (Pgp\/ABCB1), multidrug resistance\u2010related proteins and breast cancer resistance protein (BCRP\/ABCG2) in BBB cells. The aim of this study was to convert poorly permeant drugs like doxorubicin into drugs able to cross the BBB.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> Experiments were performed on primary human cerebral microvascular endothelial hCMEC\/D3 cells, alone and co\u2010cultured with human brain and epithelial tumour cells.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Statins reduced the efflux activity of Pgp\/ABCB1 and BCRP\/ABCG2 in hCMEC\/D3 cells by increasing the synthesis of NO, which elicits the nitration of critical tyrosine residues on these transporters. Statins also increased the number of low\u2010density lipoprotein (LDL) receptors exposed on the surface of BBB cells, as well as on tumour cells like human glioblastoma. We showed that the association of statins plus drug\u2010loaded nanoparticles engineered as LDLs was effective as a vehicle for non\u2010permeant drugs like doxorubicin to cross the BBB, allowing its delivery into primary and metastatic brain tumour cells and to achieve significant anti\u2010tumour cytotoxicity.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> We suggest that our \u2018Trojan horse\u2019 approach, based on the administration of statins plus a LDL receptor\u2010targeted liposomal drug, might have potential applications in the pharmacological therapy of different brain diseases for which the BBB represents an obstacle.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.02103.x","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T23:56:25Z","timestamp":1342137385000},"page":"1431-1447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["The association of 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