Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells.
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2017-03-01
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Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 μM PolyGem was equivalent in tumor cell toxicity to 1 μM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.
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Sood, Nimil, Walter T Jenkins, Xiang-Yang Yang, Nikesh N Shah, Joshua S Katz, Cameron J Koch, Paul R Frail, Michael J Therien, et al. (2017). Biodegradable Polymersomes for the Delivery of Gemcitabine to Panc-1 Cells. J Pharm (Cairo), 2013. 10.1155/2013/932797 Retrieved from https://hdl.handle.net/10161/13734.
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Scholars@Duke
Michael J. Therien
Our research involves the synthesis of compounds, supermolecular assemblies, nano-scale objects, and electronic materials with unusual ground-and excited-state characteristics, and interrogating these structures using state-of-the-art transient optical, spectroscopic, photophysical, and electrochemical methods. Research activities span physical inorganic chemistry, physical organic chemistry, synthetic chemistry, bioinorganic chemistry, spectroscopy, photophysics, excited-state dynamics, spintronics, and imaging. My laboratory: (i) designs chromophores and supermolecules that display exceptional opto-electronic properties and elucidates their excited-state dynamics, (ii) engineers highly conjugated molecular structures for optical limiting, specialized emission, and high charge mobility, (iii) designs conjugated materials and hybrid molecular-nanoscale structures for energy conversion reactions, (iv) develops molecular wires that propagate spin-polarized currents, (v) fabricates emissive nanoscale structures for in vivo optical imaging, (vi) engineers de novo transition metal cofactor-binding proteins that test light-driven biological energy transducing mechanisms and realize opto-electronic functionalities not found in nature, and (vii) designs and interrogates complex molecular and nanoscale assemblies in which ultrafast energy and charge migration reactions are controlled by quantum coherence effects.
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