title: Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells.
abstract: Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they also demonstrate a slow release for the encapsulated contents, limiting their efficacy as a drug-delivery tool. As a solution, we prepared and characterized echogenic polymersomes, which are programmed to release the encapsulated drugs rapidly when incubated with cytosolic concentrations of glutathione. These vesicles encapsulated air bubbles inside and efficiently reflected diagnostic-frequency ultrasound. Folate-targeted polymersomes showed an enhanced uptake by breast and pancreatic-cancer cells in a monolayer as well as in three-dimensional spheroid cultures. Polymersomes encapsulated with the anticancer drugs gemcitabine and doxorubicin showed significant cytotoxicity to these cells. With further improvements, these vesicles hold the promise to serve as multifunctional nanocarriers, offering a triggered release as well as diagnostic ultrasound imaging.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Nahire
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Manas K
authors.initials: MK
authors.lastname: Haldar
authors.affiliation: Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, United States.
authors.forename: Shirshendu
authors.initials: S
authors.lastname: Paul
authors.affiliation: Civil Engineering, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Avinash H
authors.initials: AH
authors.lastname: Ambre
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Varsha
authors.initials: V
authors.lastname: Meghnani
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Buddhadev
authors.initials: B
authors.lastname: Layek
authors.affiliation: Civil Engineering, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Kalpana S
authors.initials: KS
authors.lastname: Katti
authors.affiliation: Health, Nutrition, and Exercise Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Kara N
authors.initials: KN
authors.lastname: Gange
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States.
authors.forename: Jagdish
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, United States; Department of Mechanical and Aerospace Engineering, George Washington University, Washington, DC 20052, United States.
authors.forename: Kausik
authors.initials: K
authors.lastname: Sarkar
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, United States. Electronic address: Sanku.Mallik@ndsu.edu.
authors.forename: Sanku
authors.initials: S
authors.lastname: Mallik
mesh_terms: D000162:Acoustics; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry* / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy*; D010084:Oxidation-Reduction; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D019163:Reducing Agents / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology; D014465:Ultrasonics; D000093542:Gemcitabine
chemical_list: D005452:Fluoresceins; D008081:Liposomes; D011108:Polymers; D019163:Reducing Agents; D003841:Deoxycytidine; D004317:Doxorubicin; C007740:fluorexon; D000093542:Gemcitabine
keywords: Drug delivery; Gemcitabine; Liposome; Pancreatic cancer; Polymersome