Journal article
Nucleus-Targeted, Echogenic Polymersomes for Delivering a Cancer Sternness Inhibitor to Pancreatic Cancer Cells
Biomacromolecules, Vol.19(10), pp.4122-4132
10/01/2018
DOI: 10.1021/acs.biomac.8b01133
PMID: 30169024
Abstract
Chemotherapeutic agents for treating cancers show considerable side effects, toxicity, and drug resistance. To mitigate the problems, we designed nucleus-targeted, echogenic, stimuli-responsive polymeric vesicles (polymersomes) to transport and subsequently release the encapsulated anticancer drugs within the nuclei of pancreatic cancer cells. We synthesized an alkyne-dexamethasone derivative and conjugated it to N-3-polyethylene glycol (PEG)-polylactic acid (PLA) copolymer employing the Cu2+ catalyzed "Click" reaction. We prepared polymersomes from the dexamethasone-PEG- PLA conjugate along with a synthesized stimuli-responsive polymer PEG-S-S-PLA. The dexamethasone group dilates the nuclear pore complexes and transports the vesicles to the nuclei. We designed the polymersomes to release the encapsulated drugs in the presence of a high concentration of reducing agents in the nuclei of pancreatic cancer cells. We observed that the nucleus-targeted, stimuli-responsive polymersomes released 70% of encapsulated contents in the nucleus-mimicking environment in 80 min. We encapsulated the cancer stemness inhibitor BBI608 in the vesicles and observed that the BBI608 encapsulated polymersomes reduced the viability of the BxPC3 cells to 43% in three-dimensional spheroid cultures. The polymersomes were prepared following a special protocol so that they scatter ultrasound, allowing imaging by a medical ultrasound scanner. Therefore, these echogenic, targeted, stimuli-responsive, and drug-encapsulated polymersomes have the potential for trackable, targeted carrier of chemotherapeutic drugs to cancer cell nuclei.
Details
- Title: Subtitle
- Nucleus-Targeted, Echogenic Polymersomes for Delivering a Cancer Sternness Inhibitor to Pancreatic Cancer Cells
- Creators
- Fataneh Karandish - North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USABabak Mamnoon - North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USALi Feng - North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USAManas K. Haldar - North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USALang Xia - George Washington UniversityKara N. Gange - North Dakota State UniversitySeungyong You - North Dakota State Univ, Dept Phys, Fargo, ND 58108 USAYongki Choi - North Dakota State Univ, Dept Phys, Fargo, ND 58108 USAKausik Sarkar - George Washington UniversitySanku Mallik - North Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58108 USA
- Resource Type
- Journal article
- Publication Details
- Biomacromolecules, Vol.19(10), pp.4122-4132
- Publisher
- Amer Chemical Soc
- DOI
- 10.1021/acs.biomac.8b01133
- PMID
- 30169024
- ISSN
- 1525-7797
- eISSN
- 1526-4602
- Number of pages
- 11
- Grant note
- Grand Challenge Initiative, North Dakota State University Office of the Vice President for Research and Creative Activity, North Dakota State University 1 R01GM 114080 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM114080 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DMR 1306154 / NSF; National Science Foundation (NSF)
- Language
- English
- Date published
- 10/01/2018
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984303968402771
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