Dual Stimuli-Responsive Nucleobase-Functionalized Polymeric Systems as Efficient Tools for Manipulating Micellar Self-Assembly Behavior

Abstract

Environmental stimuli-responsive nucleobase-functionalized supramolecular polymers, a combination of oligomeric polypropylene glycol segments as a thermosensitive element and hydrogen-bonded uracil as a photosensitive moiety, were successfully developed and undergo spontaneous self-assembly to form uniform nanosized micelles via self-complementary double hydrogen bonding interactions between the uracil moieties in an aqueous environment. These micelles exhibit unique properties such as dual thermo-and photoresponsiveness, controllable lower critical concentration solution temperature (LCST), photoreactivity, and morphological transformation, making them highly attractive for various applications. More importantly, phase transitions and morphological studies confirmed the LCST behavior, size, and shape of the micelles can be easily tuned by adjusting the concentration and duration of ultraviolet irradiation of samples in aqueous solution, indicating introduction of uracil molecules into a water-soluble polymer matrix may represent a promising approach toward development of multiple stimuliresponsive polymeric micelles whose self-assembly behavior can be manipulated. In view of the ease of fabrication, high biocompatibility, multifunctionality, and tailorable micellar properties, this newly developed supramolecular micelle may be a promising candidate nanocarrier for controlled drug delivery and bioimaging systems.

Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy

“…During ultraviolet (UV) irradiation (254 nm, 50−70 mW/cm 2 ), the intensity of the C=C double bond absorbance peak at 263 nm in the UV-Vis spectra of BU-PPG solution gradually decreased due to the [2π + 2π] photocycloaddition reaction between uracil groups. The peak eventually leveled off after 60 min irradiation ( Figure S1) [42], indicating BU-PPG was almost completely photo-dimerized (calculated conversion efficiency of 95%), in good agreement with previous experimental results (96%) [40]. After encapsulating DOX at a 1:1 polymer/drug weight ratio by a dialysis method, the average particle diameters of irradiated and non-irradiated BU-PPG micelles increased from 141 nm and 148 nm to 180 nm and 189 nm, with DLC values of 24.6% and 18.4%, respectively ( Figure S2 and Table S1).…”

“…The chemical structures of non-irradiated and irradiated BU-PPG polymers and their spontaneous self-organization into spherical nanosized micelles in water via formation of photo-dimerized uracil and hydrogen-bonded uracil dimers are presented in Scheme 1 [40,41]. Uracil end-capped difunctional oligomeric BU-PPG was successfully prepared by a simple one-step Michael addition reaction of PPG diacrylate (weight-average molecular weight of 800 g/mol, approximately 12 repeating units) to uracil, as described in our earlier report [40]. Doxorubicin (DOX) was selected as a chemotherapeutic drug and loaded into non-irradiated and irradiated BU-PPG micelles.…”

“…In our previous studies, we synthesized an intelligent supramolecular polypropylene glycol (PPG) that possesses difunctional uracil-containing end groups (BU-PPG) by a simple one-step Michael addition reaction [40,41]. BU-PPG spontaneously assembles into thermo-sensitive nano-sized supramolecular micelles-both before and after photoirradiation-in aqueous solution.…”

Optically responsive delivery platforms: from the design considerations to biomedical applications

“…This results in the release of the pre-encapsulated drug. In the recent study, dual-responsive polymeric micelles were designed using photodimerisation process, which were capable of tuning the LCST of the polymer by attaching photosensitive moieties [174].…”

Optically Active Nucleobase-Functionalized Polynorbornenes Mimicking Double-Helix DNA

“…[40][41][42] This temperaturesensitive property originated from the H-bonds between the nucleobases. 24,43,44 It was well known that the circular dichroism (CD) technique was very sensitive to the helical structure of DNA in solution. Acetonitrile was also used to study the CD spectra.…”