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

Prajakta Kulkarni; Manas K Haldar; Fataneh Karandish; Matthew Confeld; Rayat Hossain; Pawel Borowicz; Kara Gange; Lang Xia; Kausik Sarkar; Sanku Mallik

doi:10.1002/chem.201802229

Journal article

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

Prajakta Kulkarni, Manas K Haldar, Fataneh Karandish, Matthew Confeld, Rayat Hossain, Pawel Borowicz, Kara Gange, Lang Xia, Kausik Sarkar and Sanku Mallik

Chemistry : a European journal, Vol.24(48), pp.12490-12494

08/27/2018

DOI: 10.1002/chem.201802229

PMID: 29968262

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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.

Animals

Antineoplastic Agents - administration & dosage

Antineoplastic Agents - chemistry

Azo Compounds - chemistry

Cell Line, Tumor

Cell Survival - drug effects

Deoxycytidine - administration & dosage

Deoxycytidine - analogs & derivatives

Deoxycytidine - chemistry

Drug Carriers - chemistry

Drug Liberation

Heterografts

Humans

Lactates - chemistry

Male

Mice, Nude

Microsomes, Liver - metabolism

Nanoparticles - chemistry

Oligopeptides - chemistry

Pancreatic Neoplasms - diagnostic imaging

Pancreatic Neoplasms - drug therapy

Particle Size

Polyethylene Glycols - chemistry

Rats

Tumor Hypoxia

Details

Title: Subtitle: Tissue-Penetrating, Hypoxia-Responsive Echogenic Polymersomes For Drug Delivery To Solid Tumors
Creators: Prajakta Kulkarni - North Dakota State University
Manas K Haldar - North Dakota State University
Fataneh Karandish - North Dakota State University
Matthew Confeld - North Dakota State University
Rayat Hossain - North Dakota State University
Pawel Borowicz - North Dakota State University
Kara Gange - North Dakota State University
Lang Xia - George Washington University
Kausik Sarkar - George Washington University
Sanku Mallik - North Dakota State University
Resource Type: Journal article
Publication Details: Chemistry : a European journal, Vol.24(48), pp.12490-12494
DOI: 10.1002/chem.201802229
PMID: 29968262
ISSN: 0947-6539
eISSN: 1521-3765
Grant note: DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: 1R01GM114080, 1P20GM109024
Language: English
Date published: 08/27/2018
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9984304707902771

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