Τίτλος:
A triphenylphosphonium-functionalized mitochondriotropic nanocarrier for efficient co-delivery of doxorubicin and chloroquine and enhanced antineoplastic activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication. The anticancer activity of this system against two aggressive DOX-resistant human prostate adenocarcinoma cell lines and in in vivo animal studies was assessed. The co-administration of encapsulated DOX and CQ leads to improved cell proliferation inhibition at extremely low DOX concentrations (0.25 μM). In vivo experiments against DU145 human prostate cancer cells grafted on immunodeficient mice resulted in tumor growth arrest during the three-week administration period and no pervasive side effects. The findings put forward the potential of such targeted low dose combination treatments as a therapeutic scheme with minimal adverse effects. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Panagiotaki, K.N.
Sideratou, Z.
Vlahopoulos, S.A.
Paravatou-Petsotas, M.
Zachariadis, M.
Khoury, N.
Zoumpourlis, V.
Tsiourvas, D.
Λέξεις-κλειδιά:
chloroquine; doxorubicin; nanocarrier; phosphonium derivative; polyethyleneimine; triphenylphosphonium; unclassified drug, animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer inhibition; cell proliferation; cell viability; concentration response; confocal laser scanning microscopy; controlled study; drug delivery system; drug effect; drug potency; DU145 cell line; human; human cell; male; mouse; nanoencapsulation; nanopharmaceutics; nonhuman; particle size; prostate adenocarcinoma
