title: Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(β-l-malic acid).
abstract: Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-l-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Patil
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Portilla-Arias
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Konda
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Rekechenetskiy
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.|Institut für Biophysik und Physikalische Biochemie der Universität Regensburg, Regensburg 93053, Germany.
authors.forename: Eggehard
authors.initials: E
authors.lastname: Holler
authors.affiliation: Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, 110 N. George Burns Rd. Davis Building, Room 2094-A, Los Angeles, CA 90048, USA.
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Ljubimova
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008293:Malates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D058726:Nanoconjugates / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D006835:Hydrazones; D008293:Malates; D058726:Nanoconjugates; D011108:Polymers; C074640:poly(malate); D004317:Doxorubicin
keywords: brain and breast cancer; doxorubicin; nanoconjugate; pH-controlled hydrazine linkage; polymalic acid