Jyun-Jie Huang

Stimuli-responsive single-chain polymeric nanoparticles towards the development of efficient drug delivery systems

Novel multifunctional single-chain polymeric nanoparticles not only significantly improve drug transport efficiency in vitro but can also reside stably and facilitate precisely-triggered drug-release in tumor-like microenvironments, thus providing new insights into the development of drug-loaded SCNPs for controlled drug delivery applications.

Nucleobase‐Functionalized Supramolecular Micelles with Tunable Physical Properties for Efficient Controlled Drug Release

Complementary nucleobase-functionalized polymeric micelles, a combination of adenine-thymine (A-U) base pairs and a blend of hydrophilic-hydrophobic polymer pairs, can be used to construct 3D supramolecular polymer networks; these micelles exhibit excellent self-assembly ability in aqueous solution, rapid pH-responsiveness, high drug loading capacity, and triggerable drug release. In this study, a multi-uracil functionalized poly(ε-caprolactone) (U-PCL) and adenine end-capped difunctional oligomeric poly(ethylene glycol) (BA-PEG) are successfully developed and show high affinity and specific recognition in solution owing to dynamically reversible A-U-induced formation of physical cross-links. The U-PCL/BA-PEG blend system produces supramolecular micelles that can be readily adjusted to provide the desired critical micellization concentration, particle size, and stability. Importantly, in vitro release studies show that doxorubicin (DOX)-loaded micelles exhibit excellent DOX-encapsulated stability under physiological conditions. When the pH value of the solution is reduced from 7.4 to 5.0, DOX-loaded micelles can be rapidly triggered to release encapsulated DOX, suggesting these polymeric micelles represent promising candidate pH-responsive nanocarriers for controlled-release drug delivery and pharmaceutical applications.

Supramolecular fluorescent nanoparticles functionalized with controllable physical properties and temperature-responsive release behavior

Supramolecular fluorescent nanoparticles (SFNs), a combination of hydrogen-bonded supramolecular macromers and fluorescent pyrene dyes, can spontaneously self-assemble into thermosensitive micelles in an aqueous environment; the resulting micelles exhibit unique thermo-responsiveness and tunable phase transition behavior, making them highly attractive for the development of next-generation biomedical imaging tools and smart drug delivery applications. Herein, we developed a low-molecular-weight supramolecular polymer, adenine end-capped difunctional polypropylene glycol (BA-PPG), containing an adenine multiple hydrogen bonding moiety that effectively encapsulates pyrene molecules to generate the desired nanoparticle size, pyrene-loading content, and fluorescence properties in aqueous solution. Importantly, pyrene-loaded BA-PPG micelles act as a stable nanocarrier to greatly improve the pyrene-entrapment stability and generate high green-colored excimer emission under physiological conditions. Increasing the temperature above the lower critical solution temperature (45 °C) triggered a rapid release of the encapsulated pyrene from the loaded micelles due to the dissociation of the dynamic hydrogen bonds between adenine moieties, leading to the release of pyrene into aqueous solution and a gradual decrease in pyrene excimer emission. Given its simplicity of fabrication, low cost, high efficiency and multi-functionality, this newly-developed temperature-responsive micelle offers a new pathway for the development of high-efficiency SFNs.

Dynamic supramolecular self-assembly: hydrogen bonding-induced contraction and extension of functional polymers

Simple construction and manipulation of low-molecular-weight supramolecular polymers, based on incorporation of self-complementary multiple hydrogen bonding interactions, with the desired dynamic response characteristics to achieve high-efficiency supramolecular assembly and control the morphological properties of the polymers remain highly challenging. Herein, we developed a new difunctional telechelic supramolecular polymer (UrCy-PPG) containing self-complementary quadruple hydrogen-bonded ureido-cytosine (UrCy) moieties, which spontaneously self-assembles to form long-range-ordered lamellar structures in the bulk state. Scattering and rheological studies confirmed that the dynamic behavior of UrCy units induces structural phase transitions from quadruple to dual hydrogen-bonded arrays, leading to well-controlled, self-organized supramolecular nanostructure morphologies. The microstructural features could be easily tuned by altering environmental conditions, making the self-assembly processes highly efficient. Importantly, temperature/shear stress-dependent microstructural analyses indicated that UrCy-PPG has the capacity to manipulate the transition between contractile and fully extended lamellar structures. Given its novelty, simple synthesis, high reliability, and efficient self-assembly processes, this newly developed supramolecular polymer represents a new concept and pathway for controlled arrangement of self-assembled polymeric nanostructures.

Self-Assembled Supramolecular Nanogels as a Safe and Effective Drug Delivery Vector for Cancer Therapy

Simple construction and manipulation of low-molecular-weight supramolecular nanogels, based on the introduction of multiple hydrogen bonding interactions, with the desired physical properties to achieve effective and safe delivery of drugs for cancer therapy remain highly challenging. Herein, a novel supramolecular oligomer cytosine (Cy)-polypropylene glycol containing self-complementary multiple hydrogen-bonded Cy moieties is developed, which undergoes spontaneous self-assembly to form nanosized particles in an aqueous environment. Phase transitions and scattering studies confirm that the supramolecular nanogels can be readily tailored to obtain the desired phase-transition temperature and temperature-induced release of the anticancer drug doxorubicin (DOX). The resulting nanogels exhibit an extremely high load carrying capacity (up to 24.8%) and drug-entrapment stability, making the loading processes highly efficient. Importantly, in vitro cytotoxicity assays indicate that DOX-loaded nanogels possess excellent biosafety for drug delivery applications under physiological conditions. When the environmental temperature is increased to 40 °C, DOX-loaded nanogels trigger rapid DOX release and exert cytotoxic effects, significantly reducing the dose required compared to free DOX. Given its simplicity, low cost, high reliability, and efficiency, this newly developed temperature-responsive nanocarrier has highly promising potential for controlled release drug delivery systems.

Complementary hydrogen bonding interaction-mediated hole injection in organic light-emitting devices

Nucleobase-functionalized conjugated polymers (NCPs) utilize molecular self-assembly to spontaneously arrange into three-dimensional supramolecular polymer networks through complementary multiple hydrogen bonding interactions. NCPs behave as a highly efficient optoelectronic material with substantially enhanced overall physical properties, making them highly attractive for a wide range of optical and electronic applications. Due to the ease of varying the extent of the reversible network by tuning the complementary base pairing content, these newly-developed NCPs could be easily tailored to meet specific requirements with respect to thermal stability, optical properties and energy band gaps for the fabrication of organic light emitting diode (OLED) devices. When NCPs were employed as the hole injection layer (HIL) in a solution-processed three-layer OLED device, a low turn-on voltage (2.9 V), maximum brightness as high as ∼52 000 cd m−2 and a luminous efficiency of 9.7 cd A−1 were achieved; these values were much higher than those of control samples and conventional HIL-based devices. Thus, this new system provides a new direction to further improve the hole-injection ability of conjugated polymers and hence offers opportunities towards the design and development of high-performance multilayer OLED devices.

Nucleobase-functionalized supramolecular polymer films with tailorable properties and tunable biodegradation rates

Biodegradable nucleobase-functionalized supramolecular polymers have been successfully developed and undergo effective spontaneous assembly into a non-covalently cross-linked three-dimensional network structure with excellent film-forming ability, tuned physical properties and biodegradation rates, making them particularly attractive for use as biopolymer-based scaffolds and regenerative medicine applications.

Water-soluble fullerene-functionalized polymer micelles for efficient aqueous-processed conductive devices

This study represents an important discovery that employs donor–acceptor (D–A) energy transfer-based strategies to construct water-soluble hybrid micelles with hydrophilic sodium ion-functionalized polythiophene (PTA-Na) as a donor and hydrophobic fullerene (C60) as an acceptor, enabling the production of multifunctional self-assembled micelles for applications in environmentally friendly electronic devices. The C60-loaded micelles exhibit uniform nanospherical shape and morphology, tunable C60 loading capacity and excellent C60-entrapment stability, in combination with unique electrochemical properties due to highly efficient D–A energy transfer from PTA-Na to C60. In addition, spin-coated PTA-Na/C60 film possessed superior electrical conductivity of up to 1.85 × 10−1 S cm−1, nearly one order of magnitude higher than that of pristine PTA-Na film under the same experimental conditions. More importantly, when PTA-Na/C60 micelles were employed as the conducting layer in an aqueous-processed single-layer conductive device, the resulting device exhibited substantially higher electrical performance than control PTA-Na and C60 devices. Given its simplicity of fabrication, multifunctional properties, high efficiency and environmentally friendly characteristics, this newly-developed water-soluble heterojunction material provides a new route to enable the development of high-performance aqueous-processed electronic devices.