Journal
BIOMACROMOLECULES
Volume 22, Issue 12, Pages 5307-5318Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.1c01199
Keywords
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Funding
- Ministry of Science and Technology, Taiwan [MOST 110-2221-E011-003-MY3]
- National Taiwan University of Science and Technology-Taipei Medical University Joint Research Program [TMU-NTUST-110-04]
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The study successfully obtained a high yield difunctional cytosine-terminated supramolecular macromer, which forms nanosized spherical micelles with excellent structural stability and drug release performance after UV irradiation. Further in vitro studies demonstrated that the photodimerized cytosine moieties enhance the cellular uptake and induce apoptotic cell death of the drug-loaded micelles.
Design, fabrication, and control of photoreactive supramolecular macromers-which are composed of a thermoresponsive polymer backbone and photoreactive nucleobase end-groups-to achieve the desired physical-chemical performance and provide the high efficiency required for chemotherapy drug delivery purposes still present challenges. Herein, a difunctional cytosine-terminated supramolecular macromer was successfully obtained at high yield. UV-irradiation induces the formation of cytosine photodimers within the structure. The irradiated macromer can self-assemble into nanosized spherical micelles in water that possess a number of interesting and unique features, such as desired micellar size and morphology, tunable drug-loading capacity, and excellent structural stability in serum-containing medium, in addition to well-controlled drug-release behaviors in response to changes in environmental temperature and pH; these extremely desirable, rare features are required to augment the functions of polymeric nanocarriers for drug delivery. Importantly, a series of in vitro studies demonstrated that photodimerized cytosine moieties within the drug-loaded micelles substantially enhance their internalization and accumulation inside cells via endocytosis and subsequently lead to induction of massive apoptotic cell death compared with the corresponding nonirradiated micelles. Thus, this newly developed photomodified nanocarrier system could provide a potentially fruitful route to enhance the drug delivery performance of nanocages without the need to introduce targeting moieties or additional components.
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