title: A Novel Pseudo-Protein-Based Biodegradable Nanomicellar Platform for the Delivery of Anticancer Drugs.
abstract: Amino acid-based poly(ester amide)s are a new family of biodegradable polymers that exhibit "pseudo-protein" characteristics and the structural varieties of poly(ester amide)s make them hold great potential in multiple biomedical applications. In this study, a lysine-phenylalanine-based pseudo-protein is developed as the self-assembled nanomicellar carrier for efficient delivery of doxorubicin. The lysine moieties from the pseudo-protein provide available sites for further functionalization, and methylcoumarin is introduced for easy and photocontrollable crosslinking, to effectively improve the micellar stability in serum containing environment and against dilution. However, photocrosslinks do not bring in any barrier for the intracellular release of doxoubicin. Doxorubicin release is significantly accelerated by proteolytic enzyme, due to the biodegradability of pseudo-protein micelles. In addition, pseudo-protein delivery system exhibits unique interactions with HCT116 human colon cancer cells. Doxorubicin loaded in pseudo-protein micelles colocalizes with mitochondria and endolysosomes, while free doxorubicin is distributed only in the nuclei. Doxorubicin-loaded pseudo-protein micelles stimulate increased level of intracellular reactive oxygen species and mitochondrial damage. Free doxorubicin induces conditional apoptosis in HCT116 cells between 0.5× 10-6and 2 × 10-6m, while DOX loaded in pseudo-protein micelles induces apoptosis over a higher/broader concentration range (2 × 10-6-10 × 10-6m).
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY, 14853-4401, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Biomedical Engineering FieldMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853-4401, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY, 14853-4401, USA.
authors.forename: Mingyu
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY, 14853-4401, USA.|Biomedical Engineering FieldMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853-4401, USA.
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Chu
mesh_terms: D000577:Amides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008823:Micelles; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D053758:Nanoparticles / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D044967:Serum / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D008823:Micelles; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011091:Polyesters; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: cancer; coumarinn; doxorubicin; drug delivery; micelles; poly(ester amide)s; reversible photo-crosslinking