Photoreactive Cytosine-Functionalized Self-Assembled Micelles with Enhanced Cellular Uptake Capability for Efficient Cancer Chemotherapy

Abere Habtamu Manayia, Fasih Bintang Ilhami, Ai Wei Lee, Chih Chia Cheng

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5307-5318
Number of pages12
JournalBiomacromolecules
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 13 2021

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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