Microfluidic preparation of monodisperse PLGA-PEG/PLGA microspheres with controllable morphology for drug release.

Monodisperse biodegradable polymer microspheres show broad applications in drug delivery and other fields. In this study, we developed an effective method that combines microfluidics with interfacial instability to prepare monodispersed poly(lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG)/poly(lactic-co-glycolic acid) (PLGA) microspheres with tailored surface morphology. By adjusting the mass ratio of PLGA-PEG to PLGA, the concentration of stabilizers and the type of PLGA, we generated microspheres with various unique folded morphologies, such as "fishtail-like", "lace-like" and "sponge-like" porous structures. Additionally, we demonstrated that risperidone-loaded PLGA-PEG/PLGA microspheres with these folded morphologies significantly enhanced drug release, particularly in the initial stage, by exhibiting a logarithmic release profile. This feature could potentially address the issue of delayed release commonly observed in sustained-release formulations. This study presents a straightforward yet effective approach to construct precisely engineered microspheres offering enhanced control over drug release dynamics.

Docetaxel-Encapsulated Catalytic Pt/Au Nanotubes for Synergistic Chemo-Photothermal Therapy of Triple-Negative Breast Cancer.

The combination of photothermal therapy with chemotherapy has emerged as a promising therapeutic modality for addressing triple-negative breast cancer (TNBC). This manuscript describes a novel hybrid nanoplatform comprising ultrathin catalytic platinum/gold (Pt/Au) nanotubes encapsulated with docetaxel and phase-change materials (PCMs) for the photoacoustic imaging-guided synergistic chemo-photothermal therapy of TNBC. Upon irradiation of near-infrared laser, the photothermal heating of nanotubes converts solid-state PCM into liquid, triggering the controlled release of the encapsulated docetaxel. The thin Pt layer within nanotubes enhances the nanotube's thermal stability, thus prolonging the photothermal ablation of tumors. Furthermore, platinum effectively mitigates tumor hypoxia by catalyzing the decomposition of hydrogen peroxides to generate oxygen in the tumor microenvironment, thus improving the efficiency of chemotherapy. It is demonstrated that the drug-loaded nanotubes achieve significant tumor inhibition rates of 75.4% in vivo on 4T1 tumor-bearing mice, significantly surpassing control groups. These nanotubes also notably extend survival, attributable to the synergistic effects of prolonged photothermal therapy facilitated by platinum and oxygenation-enhanced chemotherapy. This combination leverages the unique properties of the Pt/Au NTs-DTX/PCM nanoplatform, optimizing therapeutic outcomes. It is envisioned that this nanoplatform may find important applications in managing superficial malignant solid tumors in general.

Engineering the Electrostatic Interactions between Oppositely Charged Polymer-Grafted Nanoparticles for Constructing Colloid Molecules on Substrates.

Arrays of nanoparticle (NP) clusters with controlled architectures show broad applications in nanolasers, sensors, and photocatalysis, but the fabrication of these arrays on substrates remains a grand challenge. This review presents a highly effective polymer-based strategy for the process-directed self-assembly of binary polyelectrolyte-grafted NPs (PGNPs) bearing opposite charges into stable colloidal molecules (CMs) on substrates via electrostatic interactions. The coordination number (x) of ABx CMs can be tuned by adjusting the pH or ionic strength of the solution or by employing different combinations of PGNPs with varying charge densities. Large-area CMs with diverse structures ranging from AB to AB7 can be constructed on substrates in high yields. This approach is applicable to PGNPs with different cores of NPs. This assembly strategy offers a useful tool for the fabrication of structurally precise assemblies on substrates with broad applications.

Hierarchically Responsive Alternating Nano-Copolymers with Tailored Interparticle Bonds.

Self-assembly of inorganic nanoparticles (NPs) is an essential tool for constructing structured materials with a wide range of applications. However, achieving ordered assembly structures with externally programmable properties in binary NP systems remains challenging. In this work, we assemble binary inorganic NPs into hierarchically pH-responsive alternating copolymer-like nanostructures in an aqueous medium by engineering the interparticle electrostatic interactions. The polymer-grafted NPs bearing opposite charges are viewed as nanoscale monomers ("nanomers"), and copolymerized into alternating nano-copolymers (ANCPs) driven by the formation of interparticle "bonds" between nanomers. The resulting ANCPs exhibit reversibly responsive "bond" length (i.e., the distance between nanomers) in response to the variation of pH in a range of ~7-10, allowing precise control over the surface plasmon resonance of ANCPs. Moreover, specific interparticle "bonds" can break up at pH≥11, leading to the dis-assembly of ANCPs into molecule-like dimers and trimers. These dimeric and trimeric structures can reassemble to form ANCPs owing to the resuming of interparticle "bonds", when the pH value of the solution changes from 11 to 7. The hierarchically responsive nanostructures may find applications in such as biosensing, optical waveguide, and electronic devices.

Photo-Induced Self-assembly of Copolymer-Capped Nanoparticles into Colloidal Molecules.

Colloidal molecules (CMs) are precisely defined assemblies of nanoparticles (NPs) that mimic the structure of real molecules, but externally programming the precise self-assembly of CMs is still challenging. In this work, we show that the photo-induced self-assembly of complementary copolymer-capped binary NPs can be precisely controlled to form clustered ABx or linear (AB)y CMs at high yield (x is the coordination number of NP-Bs, and y is the repeating unit number of AB clusters). Under UV light irradiation, photolabile p-methoxyphenacyl groups of copolymers on NP-A*s are converted to carboxyl groups (NP-A), which react with tertiary amines of copolymers on NP-B to trigger the directional NP bonding. The x value of ABx can be precisely controlled between 1 and 3 by varying the irradiation duration and hence the amount of carboxyl groups generated on NP-As. Moreover, when NP-A* and NP-B are irradiated after mixing, the assembly process generates AB clusters or linear (AB)y structures with alternating sequence of the binary NPs. This assembly approach offers a simple yet non-invasive way to externally regulate the formation of various CMs on demand without the need of redesigning the surface chemistry of NPs for use in drug delivery, diagnostics, optoelectronics, and plasmonic devices.

Highly Conductive Topologically Chiral Molecular Knots as Efficient Spin Filters.

Knot-like structures were found to have interesting magnetic properties in condensed matter physics. Herein, we report on topologically chiral molecular knots as efficient spintronic chiral material. The discovery of the chiral-induced spin selectivity (CISS) effect opens the possibility of manipulating the spin orientation with soft materials at room temperature and eliminating the need for a ferromagnetic electrode. In the chiral molecular trefoil knot, there are no stereogenic carbon atoms, and chirality results from the spatial arrangements of crossings in the trefoil knot structures. The molecules show a very high spin polarization of nearly 90%, a conductivity that is higher by about 2 orders of magnitude compared with that of other chiral small molecules, and enhanced thermal stability. A plausible explanation for these special properties is provided, combined with model calculations, that supports the role of electron-electron interaction in these systems.

Chirality-induced avalanche magnetization of magnetite by an RNA precursor.

Homochirality is a hallmark of life on Earth. To achieve and maintain homochirality within a prebiotic network, the presence of an environmental factor acting as a chiral agent and providing a persistent chiral bias to prebiotic chemistry is highly advantageous. Magnetized surfaces are prebiotically plausible chiral agents due to the chiral-induced spin selectivity (CISS) effect, and they were utilized to attain homochiral ribose-aminooxazoline (RAO), an RNA precursor. However, natural magnetic minerals are typically weakly magnetized, necessitating mechanisms to enhance their magnetization for their use as effective chiral agents. Here, we report the magnetization of magnetic surfaces by crystallizing enantiopure RAO, whereby chiral molecules induce a uniform surface magnetization due to the CISS effect, which spreads across the magnetic surface akin to an avalanche. Chirality-induced avalanche magnetization enables a feedback between chiral molecules and magnetic surfaces, which can amplify a weak magnetization and allow for highly efficient spin-selective processes on magnetic minerals.

Effect of Anesthesia Gases on the Oxygen Reduction Reaction.

The oxygen reduction reaction (ORR) is of high importance, among others, because of its role in cellular respiration and in the operation of fuel cells. Recently, a possible relation between respiration and general anesthesia has been found. This work aims to explore whether anesthesia related gases affect the ORR. In ORR, oxygen which is in its triplet ground state is reduced to form products that are all in the singlet state. While this process is "in principle" forbidden because of spin conservation, it is known that if the electrons transferred in the ORR are spin-polarized, the reaction occurs efficiently. Here we show, in electrochemical experiments, that the efficiency of the oxygen reduction is reduced by the presence of general anesthetics in solution. We suggest that a spin-orbit coupling to the anesthetics depolarizes the spins. This causes both a reduction in reaction efficiency and a change in the reaction products. The findings may point to a possible relation between ORR efficiency and anesthetic action.

Ultrasound-Directed Symmetry Breaking and Spin Filtering of Supramolecular Assemblies from only Achiral Building Blocks.

Herein we describe the self-assembly of an achiral molecule into macroscopic helicity as well as the emergent chiral-selective spin-filtering effect. It was found that a benzene-1,3,5-tricarboxamide (BTA) motif with an aminopyridine group in each arm could coordinate with AgI and self-assemble into nanospheres. Upon sonication, symmetry breaking occurred and the nanospheres transferred into helical nanofibers with strong CD signals. Although the sign of the CD signals appeared randomly, it could be controlled by using the as-made chiral assemblies as a seed. Furthermore, it was found that the charge transport of the helical nanofibers was highly selective with a spin-polarization transport of up to 45 %, although the chiral nanofibers are composed exclusively from achiral building blocks. This work demonstrates symmetry breaking under sonication and the chiral-selective spin-filtering effect.

Chirality enhances oxygen reduction.

Controlled reduction of oxygen is important for developing clean energy technologies, such as fuel cells, and is vital to the existence of aerobic organisms. The process starts with oxygen in a triplet ground state and ends with products that are all in singlet states. Hence, spin constraints in the oxygen reduction must be considered. Here, we show that the electron transfer efficiency from chiral electrodes to oxygen (oxygen reduction reaction) is enhanced over that from achiral electrodes. We demonstrate lower overpotentials and higher current densities for chiral catalysts versus achiral ones. This finding holds even for electrodes composed of heavy metals with large spin-orbit coupling. The effect results from the spin selectivity conferred on the electron current by the chiral assemblies, the chiral-induced spin selectivity effect.

Homologous and Heterologous Chiral Supramolecular Polymerization from Exclusively Achiral Building Blocks.

Among the enticing issues of chiral origins are: how chirality is born from the initial achiral units and the mechanisms for the transfer of chiral information. In this work, by combining a physical vortex and chiral seeds, a general process is revealed to generate chiral supramolecular polymers from achiral C3 -symmetric molecules. The symmetry-broken assemblies from the achiral molecules could work as chiral seeds to initiate the polymerization of either homologous or heterologous achiral monomers. Concomitantly, the fragmentation of the polymer caused by the vortex during the nucleation-elongation stages is shown to enlarge the domains of the chiral nuclei and then guide the polymer to grow into the predominant helicity with a high reactivity ratio. Moreover, the chiral structural information can be stored in different forms of assemblies. These new polymerization modes will provide guidance for the preparation of chiral materials.

Hierarchical self-assembly into chiral nanostructures.

One basic principle regulating self-assembly is associated with the asymmetry of constituent building blocks or packing models. Using asymmetry to manipulate molecular-level devices and hierarchical functional materials is a promising topic in materials sciences and supramolecular chemistry. Here, exemplified by recent major achievements in chiral hierarchical self-assembly, we show how chirality may be utilized in the design, construction and evolution of highly ordered and complex chiral nanostructures. We focus on how unique functions can be developed by the exploitation of chiral nanostructures instead of single basic units. Our perspective on the future prospects of chiral nanostructures via the hierarchical self-assembly strategy is also discussed.

Steering Triplet-Triplet Annihilation Upconversion through Enantioselective Self-Assembly in a Supramolecular Gel.

Research on chiral selection and recognition not only is of fundamental importance in resolving the origin of biological homochirality, but also is instructive in the fabrication of controlled molecular organization in supramolecular systems to modulate their chirality-related functional properties. Here we report an enantioselective assembly process between a chiral energy donor and two enantiomeric energy acceptors, which further results in chirality-controlled energy transfer and enantioselective triplet-triplet annihilation upconversion (TTA-UC). It is found that the chiral energy donor Pd(II) octaethylporphyrin derivative PdOEP-LG12 (RD) can selectively coassemble with the chiral energy acceptor LGAn (RA) with the same chiral scaffold but tends to form segregation with the energy acceptor DGAn (SA) with the opposite chiral scaffold in a thermodynamic equilibrium state. Thus, the coassembly of RA/RD shows more effective triplet-triplet energy transfer (TTET) and stronger upconverted luminescence and upconverted circularly polarized luminescence in comparison to the segregation of SA/RD. The establishment of such an enantioselective TTA-UC system highlights the applications of chirality-regulated triplet fusion in optoelectronic materials.

Temperature Dependence of Charge and Spin Transfer in Azurin.

The steady-state charge and spin transfer yields were measured for three different Ru-modified azurin derivatives in protein films on silver electrodes. While the charge-transfer yields exhibit weak temperature dependences, consistent with operation of a near activation-less mechanism, the spin selectivity of the electron transfer improves as temperature increases. This enhancement of spin selectivity with temperature is explained by a vibrationally induced spin exchange interaction between the Cu(II) and its chiral ligands. These results indicate that distinct mechanisms control charge and spin transfer within proteins. As with electron charge transfer, proteins deliver polarized electron spins with a yield that depends on the protein's structure. This finding suggests a new role for protein structure in biochemical redox processes.

Steering Nanohelix and Upconverted Circularly Polarized Luminescence by Using Completely Achiral Components.

Enormous attention has been paid to upconverted circularly polarized luminescence (UC-CPL). However, so far, chiral species are still needed in UC-CPL materials, either through the covalent or noncovalent bond. Here, we report a general supramolecular coassembly approach for the fabrication of UC-CPL systems from completely achiral components. We have found that an achiral C3-symmetric molecule could form a chiral nanohelix through symmetry breaking, which could serve as a general helical platform to endow achiral guests with induced chirality and CPL activity. Two different photon upconversion systems, namely, triplet-triplet annihilation photon upconversion (TTA-UC) donor/acceptor pairs and inorganic lanthanide upconversion nanoparticles (UCNPs), are selected. When these two systems coassembled with the chiral nanohelix made from an achiral C3-symmetric molecule, hybrid nanohelix structures formed and UC-CPL activity was induced. Through such an approach, we demonstrated that the fabrication of the UC-CPL materials does not require any chiral molecules. Moreover, we have shown that the polarization of UC-CPL can be tuned by the helicity of the nanohelix, which could be controlled through the seeded vortex. Our work provides a general approach for designing tunable UC-CPL materials from completely achiral motifs, which largely expands the research scope of the CPL materials.

Circularly Polarized Luminescence in Nanoassemblies: Generation, Amplification, and Application.

Currently, the development of circularly polarized luminescent (CPL) materials has drawn extensive attention due to the numerous potential applications in optical data storage, displays, backlights in 3D displays, and so on. While the fabrication of CPL-active materials generally requires chiral luminescent molecules, the introduction of the "self-assembly" concept offers a new perspective in obtaining the CPL-active materials. Following this approach, various self-assembled materials, including organic-, inorganic-, and hybrid systems can be endowed with CPL properties. Benefiting from the advantages of self-assembly, not only chiral molecules, but also achiral species, as well as inorganic nanoparticles have potential to be self-assembled into chiral nanoassemblies showing CPL activity. In addition, the dissymmetry factor, an important parameter of CPL materials, can be enhanced through various pathways of self-assembly. Here, the present status and progress of self-assembled nanomaterials with CPL activity are reviewed. An overview of the key factors in regulating chiral emission materials at the supramolecular level will largely boost their application in multidisciplinary fields.

Asymmetric catalysis mediated by a mirror symmetry-broken helical nanoribbon.

Although chirality has been recognized as an essential entity for life, it still remains a big mystery how the homochirality in nature emerged in essential biomolecules. Certain achiral motifs are known to assemble into chiral nanostructures. In rare cases, their absolute geometries are enantiomerically biased by mirror symmetry breaking. Here we report the first example of asymmetric catalysis by using a mirror symmetry-broken helical nanoribbon as the ligand. We obtain this helical nanoribbon from a benzoic acid appended achiral benzene-1,3,5-tricarboxamide by its helical supramolecular assembly and employ it for the Cu2+-catalyzed Diels-Alder reaction. By thorough optimization of the reaction (conversion: > 99%, turnover number: ~90), the enantiomeric excess eventually reaches 46% (major/minor enantiomers = 73/27). We also confirm that the helical nanoribbon indeed carries helically twisted binding sites for Cu2+. Our achievement may provide the fundamental breakthrough for producing optically active molecules from a mixture of totally achiral motifs.

Boosting the circularly polarized luminescence of small organic molecules via multi-dimensional morphology control.

Achieving a higher dissymmetry factor is a crucial issue in developing circularly polarized luminescence (CPL) materials. Here, by tailoring the solvent composition and the morphology of the same chiral emissive small molecules (R- or S-SPAn), circularly polarized emission with a boosted dissymmetry factor (two orders) was realized. It was found that by regulating the water fraction in the mixed THF/H2O, we were able to achieve kinetic control over association of chiral emissive R- or S-SPAn into various nanostructures with 0D nanospheres, 2D nanoflakes and 3D stacked nanoflakes. These nanostructures are all CPL active. Remarkably, the dissymmetry factors of the nanostructures were significantly enhanced compared to those of the molecules and further boosted in different morphologies, from ∼10-4 (0D nanospheres) to 10-3 (2D flake) to ∼10-2 (3D nanoflakes). The enlarged g lum value could be assigned to a good packing induced strong luminescence of an excimer. This strategy provides an efficient way to fabricate higher dissymmetry factor CPL organic nanomaterials by only changing the supramolecular architectures while using the same chiral small molecules.

The chiral amine triggered self-assembly of achiral emissive molecules into circularly polarized luminescent supramolecular assemblies.

Enantiomeric diaminocyclohexane was found to trigger the self-assembly of achiral monomers into chiral supramolecular assemblies with strong circularly polarized luminescence.

Circularly polarized luminescence of achiral open-shell π-radicals.

Stable luminescent π-radicals with doublet emission have attracted growing attention for functional molecular materials. However, their chiroptical properties, particularly their doublet emission-based circularly polarized luminescence, have never been investigated. Here, we investigate the circularly polarized luminescence (CPL) properties of a series of achiral luminescent open-shell π-radicals through various chirality regulation approaches, including induction by a magnetic field, supramolecular coassembly and chiral liquid crystal encapsulation.