Pengyao Xing

Multifunctional Nanoparticles Self-Assembled from Small Organic Building Blocks for Biomedicine

Supramolecular self-assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self-assembly and materials science. The dynamic and adaptive nature of self-assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small-organic-molecule self-assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure-property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up-to-date research developments in the field are provided and research challenges to be overcome in future studies are revealed.

Superstructure Formation and Topological Evolution Achieved by Self-Organization of a Highly Adaptive Dynamer

The adaptive property of supramolecular building blocks facilitates noncovalent synthesis of soft materials. While it is still a challenging task, fine-tuning and precise control over topological nanostructures constructed from the self-assembly of low-molecular-weight building blocks are an important research direction to investigate the structure-property relationship. Herein, we report controlled self-assembly evolution of a low-molecular-weight building block bearing cholesterol and naphthalene-dicarboximide moieties, showing ultrasensitivity to solvent polarity. In low-polarity solvents (<4), it could form an M-type fiber-constituted organogel (supergel) with high solvent content, columnar molecular packing, and self-healing property. Highly polar solvents (>7.8) favor the formation of P-type helical nanostructures terminated by nanotoroids, having lamellar molecular packing. With a further increase in solvent polarity (up to 9.6), unilamellar and multilamellar vesicles were generated, which could undergo an aggregation-induced fusion process to form branched nanotubes tuned by the concentration. Self-attractive interactions between aggregates were found to be responsible for the formation of superstructures including helix-nanotoroid junctions as well as membrane-fused nanotubes.

Refined Sulfur Nanoparticles Immobilized in Metal–Organic Polyhedron as Stable Cathodes for Li–S Battery

The lithium-sulfur (Li-S) battery presents a promising rechargeable energy storage technology for the increasing energy demand in a worldwide range. However, current main challenges in Li-S battery are structural degradation and instability of the solid-electrolyte interphase caused by the dissolution of polysulfides during cycling, resulting in the corrosion and loss of active materials. Herein, we developed novel hybrids by employing metal-organic polyhedron (MOP) encapsulated PVP-functionalized sulfur nanoparticles (S@MOP), where the active sulfur component was efficiently encapsulated within the core of MOP and PVP as a surfactant was helpful to stabilize the sulfur nanoparticles and control the size and shape of corresponding hybrids during their syntheses. The amount of sulfur embedded into MOP could be controlled according to requirements. By using the S@MOP hybrids as cathodes, an obvious enhancement in the performance of Li-S battery was achieved, including high specific capacity with good cycling stability. The MOP encapsulation could enhance the utilization efficiency of sulfur. Importantly, the structure of the S@MOP hybrids was very stable, and they could last for almost 1000 cycles as cathodes in Li-S battery. Such high performance has rarely been obtained using metal-organic framework systems. The present approach opens up a promising route for further applications of MOP as host materials in electrochemical and energy storage fields.

Understanding Pathway Complexity of Organic Micro/Nanofiber Growth in Hydrogen-Bonded Coassembly of Aromatic Amino Acids

Rational engineering of one-dimensional (1D) self-assembled aggregates to produce desired materials for versatile functions remains a challenge. In this work, we report the noncovalent modulation of 1D aggregates at the micro/nanoscale using a coassembly protocol. Aromatic amino acids were employed as the model building blocks, and melamine (Mm) behaves as a modulator to form coassembly arrays with aromatic amino acids selectively. The selective self-assembly behavior between aromatic amino acids and Mm allows distinguishing and detecting Mm and aromatic amino acids from their analogues in macroscopic and microscopic scales. Dimensions and sizes of fibrous aggregates prepared from different amino acids show two opposite pathways from pristine assemblies to coassemblies induced by the addition of Mm. This pathway complexity could be controlled by the molecular conformation determined by α-positioned substituents. The developed hypothesis presents an excellent expansibility to other substrates, which may guide us to rationally design and screen 1D materials with different dimensions and sizes including the production of high-quality self-standing hydrogels.

Fast-Clearable Nanocarriers Conducting Chemo/Photothermal Combination Therapy to Inhibit Recurrence of Malignant Tumors

Inhomogeneous heating by photothermal therapy (PTT) during cancer treatment often results in the recurrence of tumors. Thus, integrating PTT with chemotherapy (CHT) may provide a complementary treatment for enhanced therapeutic efficiency. Herein, this study develops a hollow structured polymer-silica nanohybrid (HPSN) as a nanocarrier to simultaneously deliver the anticancer drug paclitaxel and photothermal agent palladium phthalocyanine to tumors through enhanced permeation and the retention effect. A combinational CHT/PTT therapy on mice bearing aggressive tumor grafts is conducted. The highly malignant tumor model, which recurs after sole treatment of PTT, can be eradicated by the combined CHT/PTT treatment. In addition, most of the off-targeted HPSN nanocarriers can be excreted through a hepatobiliary pathway in about 10 d. Serology results show that the fast-clearable HPSN can significantly reduce the side effect of the loaded paclitaxel drug. The present work provides an alternative approach for combinational cancer treatment with high therapeutic efficiency.

Responsive Prodrug Self-Assembled Vesicles for Targeted Chemotherapy in Combination with Intracellular Imaging

Targeted drug delivery systems having controlled drug release property with an inherent fluorescence reporter have drawn a lot of attention in nanomedicine. However, only very few prodrugs can be directly used to construct such delivery systems. Herein, we report that an amphiphilic chlorambucil-based prodrug consisting of a fluorescence reporter and a d-mannose targeting ligand could directly self-assemble into glutathione-responsive nanovesicles for selective cancer therapy and intracellular imaging. These nanovesicles could be dissociated to release the chlorambucil drug with obviously red-shifted fluorescence when internalized by d-mannose receptor-overexpressed MCF-7 cancer cells. In addition, the nanovesicles displayed better selectivity and higher therapy efficiency than free chlorambucil drug.

Environment-Adaptive Coassembly/Self-Sorting and Stimulus-Responsiveness Transfer Based on Cholesterol Building Blocks

Abstract Manipulating the property transfer in nanosystems is a challenging task since it requires switchable molecular packing such as separate aggregation (self‐sorting) or synergistic aggregation (coassembly). Herein, a unique manipulation of self‐sorting/coassembly aggregation and the observation of switchable stimulus‐responsiveness transfer in a two component self‐assembly system are reported. Two building blocks bearing the same cholesterol group give versatile topological structures in polar and nonpolar solvents. One building block (cholesterol conjugated cynanostilbene, CCS) consists of cholesterol conjugated with a cynanostilbene unit, and the other one (C10CN) is comprised of cholesterol connected with a naphthalimide group having a flexible long alkyl chain. Their assemblies including gel, crystalline plates, and vesicles are obtained. In gel and crystalline plate phases, the self‐sorting behavior dominates, while synergistic coassembly occurs in vesicle phase. Since CCS having the cyanostilbene group can respond to the light irradiation, it undergoes light‐induced chiral amplification. C10CN is thermally responsive, whereby its supramolecular chirality is inversed upon heating. In coassembled vesicles, it is interestingly observed that their responsiveness can be transferred by each other, i.e., the C10CN segment is sensitive to the light irradiation, while CCS is thermoresponsive. This unprecedented behavior of the property transfer may shine a light to the precise fabrication of smart materials.

Selective Coassembly of Aromatic Amino Acids to Fabricate Hydrogels with Light Irradiation‐Induced Emission for Fluorescent Imprint

Controlling the structural parameters in coassembly is crucial for the fabrication of multicomponent functional materials. Here a proof-of-concept study is presented to reveal the α-substituent effect of aromatic amino acids on their selective coassembly with bipyridine binders. With the assistance of X-ray scattering technique, it is found that individual packing in the solid state as well as bulky effect brought by α-substitution determines the occurrence of coassembly. A well-performed hydrogels based on the complexation between certain aromatic amino acids and bipyridine units are successfully constructed, providing unprecedented smart materials with light irradiation-triggered luminescence. Such hydrogels without the phase separation and photobleaching during light irradiation are able to behave fluorescent imprint materials. This study provides a suitable protocol in rationally designing amino acid residues of short peptides for fabricating self-assembled multicomponent materials. In addition, this protocol is useful in screening potential functional materials on account of diverse self-assembly behavior.

Water‐Binding‐Mediated Gelation/Crystallization and Thermosensitive Superchirality

Determination of molecular structural parameters of hydrophobic cholesterol-naphthalimide conjugates for water binding capabilities as well as their moisture-sensitive supramolecular self-assembly were revealed. Water binding was a key factor in leading trace water-induced crystallization against gelation in apolar solvent. Ordered water molecules entrapped in self-assembly arrays revealed by crystal structures behave as hydrogen-bonding linkers to facilitate three-dimensional growth into crystals rather than one-dimensional gel nanofibers. Water binding was also reflected on the supramolecular chirality inversion of vesicle self-assembly in aqueous media via heating-induced dehydration. Structural parameters that favor water binding were evaluated in detail, which could help rationally design organic building units for advancing soft materials, crystal engineering, and chiral recognition.

Programmable Multicomponent Self-Assembly Based on Aromatic Amino Acids

Construction of integrated self-assembly with ordered structures from two or more organic building blocks is currently a challenge, since it suffers from intrinsic systematic complexity and diverse competitive pathways. Here, it is reported that aromatic amino acid building units can be incorporated into two- or three-component coassembly driven primarily by hydrogen bonding interactions without the assistance of metal-ligand and macrocycle-based host-guest interactions. The key strategy is to employ a C3 -symmetric molecule with alternative hydrogen bonding donor/acceptor sites that are able to bind either carboxylic acid or pyridine appended building units. Aromatic amino acids, C3 -symmetric compound, and bipyridine unit constitute a unique ternary mutual binding system, where three coassembly pathways including two pairwise formations and one ternary combination are unveiled, giving rise to two- and three-component self-assemblies with ordered structures, respectively. The pathway complexity lies in the structural parameter of aromatic amino acids, which can be programmable by controlling substituents at the α-position of amino acids.