期刊
JOURNAL OF CONTROLLED RELEASE
卷 178, 期 -, 页码 63-68出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2014.01.014
关键词
Thermally responsive; N-isopropylacrylamide; Nanoparticle; Hydrogel; Cancer therapeutics
资金
- NCI NIH HHS [P30 CA014236, U54 CA151668] Funding Source: Medline
A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near-infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a lower critical solution temperature (LCST) above physiologic temperature, such that the material will transition from a hydrated state to a collapsed state above similar to 40 degrees C. Additionally, the silica-gold nanoshells used were designed to have a peak extinction coefficient in the NIR, where penetration of light through tissue is maximal. This heat-triggered material phase transition of the composite was found to follow exposure of NIR light, indicating the ability of the NIR absorption by the nanoshells to sufficiently drive this transition. The composite material was loaded with either doxorubicin or a DNA duplex (a model nucleic acid therapeutic), two cancer therapeutics with differing physical and chemical properties. Release of both therapeutics was dramatically enhanced by NIR light exposure, causing 2-5x increase in drug release. Drug delivery profiles were influenced by both themolecular size of the drug as well as its chemical properties. The DNA therapeutic showed slower rates of nonspecific delivery by passive diffusion due to its larger size. Additionally, only 70% of the more hydrophobic doxorubicin was released from the material, whereas the more hydrophilic DNA showed over 90% release. Further, hydrogel composites were used to deliver the doxorubicin to CT. 26-WT colon carcinoma cells, eliciting a therapeutic response. This work validates the potential application for this material in site-specific cancer therapeutic delivery. (C) 2014 Elsevier B.V. All rights reserved.
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