title: Cisplatin Cross-Linked Multifunctional Nanodrugplexes for Combination Therapy.
abstract: Combination therapy efficiently tackles cancer by hitting multiple action mechanisms. However, drugs administered, simultaneously or sequentially, may not reach the targeted sites with the desired dose and ratio. The outcomes of combination therapy could be improved with a polymeric nanoparticle, which can simultaneously transport an optimal combination of drugs. We have demonstrated a simple one-pot strategy to formulate nanomedicines based on platinum coordination and the noncovalent interactions of the drugs. A naturally occurring polymer, hyaluronan (HA), was chosen as the building scaffold to form a nanodrugplex with cisplatin and aromatic-cationic drugs. The platinum coordination between cisplatin and HA induces the formation of a nanocomplex. The aromatic-cationic drugs are tightly packed by an electrostatic interaction and π-π stacking. The nanodrugplex bears excellent flexibility in drug combination and size control. It is stable in storage and has favorable release kinetics and targeting capabilities toward CD44, a receptor for HA that is highly expressed on many types of cancer cells.
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine , 413 East 69th Street, Box 290, New York, New York 10021, United States.
authors.forename: Weiqi
authors.identifier: http://orcid.org/0000-0003-4315-6809
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine , 413 East 69th Street, Box 290, New York, New York 10021, United States.
authors.forename: Ching-Hsuan
authors.identifier: http://orcid.org/0000-0001-6648-6195
authors.initials: CH
authors.lastname: Tung
mesh_terms: D000970:Antineoplastic Agents; D002945:Cisplatin; D003432:Cross-Linking Reagents; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D050997:Nanomedicine; D053758:Nanoparticles; D011108:Polymers
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018960:Hyaluronan Receptors; D011108:Polymers; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: combination therapy; drug delivery; hyaluronan; noncovalent interactions; self-assembly