Tissue-Penetrating, Hypoxia-Responsive Echogenic Polymersomes For Drug Delivery To Solid Tumors
Autor: | Sanku Mallik, Fataneh Karandish, Kara N. Gange, Lang Xia, Matthew Confeld, Prajakta Kulkarni, Rayat Hossain, Manas K. Haldar, Kausik Sarkar, Pawel P. Borowicz |
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Rok vydání: | 2018 |
Předmět: |
Male
Cell Survival medicine.medical_treatment Mice Nude Antineoplastic Agents 02 engineering and technology Deoxycytidine Catalysis Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Pancreatic tumor Pancreatic cancer Cell Line Tumor medicine Animals Humans Particle Size Drug Carriers Chemistry Organic Chemistry Echogenicity General Chemistry Hypoxia (medical) 021001 nanoscience & nanotechnology medicine.disease Gemcitabine Rats Radiation therapy Pancreatic Neoplasms Drug Liberation 030220 oncology & carcinogenesis Polymersome Drug delivery Cancer research Lactates Microsomes Liver Heterografts Nanoparticles Tumor Hypoxia medicine.symptom 0210 nano-technology Drug carrier Azo Compounds Oligopeptides |
Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 24(48) |
ISSN: | 1521-3765 |
Popis: | 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. |
Databáze: | OpenAIRE |
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