Abstract
The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications.
Highlights
Nano-sized drug delivery systems are widely used in pharmaceutical research and the clinic to enhance the therapeutic effects of anticancer drugs [1,2,3,4]
Developments in materials science and pharmaceutics have enabled the design of various nanocarriers with diverse sizes, architectures, and surface properties that have potential as drug delivery systems, including polymers [7,8], liposomes [9], inorganic materials [10,11], and metallic colloids [12]
Polymeric micelles have attracted attention as drug delivery systems because of their good biocompatibility, controlled self-assembly behavior, and high structural stability under physiological conditions [13,14,15,16]. In spite of these advantages, existing polymeric micelles possess a number of limitations, including inefficient drug-entrapment stability, low intracellular drug release rates, and modest accumulation in the target tissues [17]
Summary
Nano-sized drug delivery systems are widely used in pharmaceutical research and the clinic to enhance the therapeutic effects of anticancer drugs [1,2,3,4]. Hydrogen bonding allows supramolecular polymer chains to rapidly self-assemble into materials with unique physical properties, such as controlled affinity, high specificity, and reversibility [21,22,23]. The present work reports an in vitro evaluation of a novel polymeric micelle prepared from a physically and chemically cross-linked supramolecular polymer that functions as a carrier for anticancer drugs and improves the intracellular drug dosages and induction of apoptosis in cancer cells.
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