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      Tissue-Penetrating, Hypoxia-Responsive Echogenic Polymersomes For Drug Delivery To Solid Tumors.

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          Abstract

          Hypoxia in solid tumors facilitates the progression of the disease, develops resistance to chemo and radiotherapy, and contributes to relapse. Due to the lack of tumor penetration, most of the reported drug carriers are unable to reach the hypoxic niches of the solid tumors. We have developed tissue-penetrating, hypoxia-responsive echogenic polymersomes to deliver anticancer drugs to solid tumors. The polymersomes are composed of a hypoxia-responsive azobenzene conjugated and a tissue penetrating peptide functionalized polylactic acid-polyethylene glycol polymer. The drug-encapsulated, hypoxia-responsive polymersomes substantially decreased the viability of pancreatic cancer cells in spheroidal cultures. Under normoxic conditions, polymersomes were echogenic at diagnostic ultrasound frequencies but lose the echogenicity under hypoxia. In-vivo imaging studies with xenograft mouse model further confirmed the ability of the polymersomes to target, penetrate, and deliver the encapsulated contents in hypoxic pancreatic tumor tissues.

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          Author and article information

          Journal
          Chemistry
          Chemistry (Weinheim an der Bergstrasse, Germany)
          Wiley
          1521-3765
          0947-6539
          Aug 27 2018
          : 24
          : 48
          Affiliations
          [1 ] Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, 58105, USA.
          [2 ] Department of Animal and Range Sciences, North Dakota State University, Fargo, North Dakota, 58105, USA.
          [3 ] Department of Health, Exercise, and Nutrition Sciences, North Dakota State University, Fargo, North Dakota, 58105, USA.
          [4 ] Mechanical and Aerospace Engineering, George Washington University, Washington, DC, 20052, USA.
          Article
          10.1002/chem.201802229
          29968262
          8a00eb8b-13fe-4366-823f-ba86f0213cea
          © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
          History

          drug delivery,hypoxia,pancreatic cancer,polymers,polymersomes

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