Poly(malic acid) nanoconjugates containing various antibodies and oligonucleotides for multitargeting drug delivery.
Nanoconjugates are emerging as promising drug-delivery vehicles because of their multimodular structure enabling them to actively target discrete cells, pass through biological barriers and simultaneously carry multiple drugs of various chemical nature. Nanoconjugates have matured from simple devices to multifunctional, biodegradable, nontoxic and nonimmunogenic constructs, capable of delivering synergistically functioning drugs in vivo. This review mainly concerns the Polycefin family of natural-derived polymeric drug-delivery devices as an example. This type of vehicle is built by hierarchic conjugation of functional groups onto the backbone of poly(malic acid), an aliphatic polyester obtained from the microorganism Physarum polycephalum. Particular Polycefin variants target human brain and breast tumors implanted into animals specifically and actively and could be detected easily by noninvasive imaging analysis. Delivery of antisense oligonucleotides to a tumor-specific angiogenic marker using Polycefin resulted in significant inhibition of tumor angiogenesis and increase of animal survival.
Ljubimova
Julia Y
JY
Cedars-Sinai Medical Center, Department of Neurosurgery, 8631 West Third Street, Suite 800E, Los Angeles, CA 90048, USA. ljubimovaj@cshs.org
Fujita
Manabu
M
Ljubimov
Alexander V
AV
Torchilin
Vladimir P
VP
Black
Keith L
KL
Holler
Eggehard
E
D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000639:trends*; D007167:Immunotherapy / Q000379:methods*; D008293:Malates / Q000737:chemistry*; D050997:Nanomedicine / Q000639:trends; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014162:Transfection / Q000379:methods
D000906:Antibodies; D008293:Malates; D009841:Oligonucleotides; D011091:Polyesters; D011108:Polymers; C121060:poly(malic acid); C511560:polycefin