Latest ArticlesTetrahedral framework nucleic acids (tFNAs), a novel class of nanodelivery carriers, demonstrate significant potential due to their well-defined topological structure, programmable molecular recognition capabilities, and exceptional biocompatibility. This article systematically reviews the dynamic behavior of tFNAs across multi-scale delivery processes. At the macroscale, it elucidates the organ accumulation and metabolism of tFNAs following various routes of administration. At the microscale, it delves into the transmembrane transport mechanisms and subcellular localization characteristics of tFNAs. Furthermore, this review discusses the current research status of strategies aimed at improving the delivery efficiency of tFNAs through active targeted modifications and proposes cutting-edge approaches to developing precision delivery systems leveraging engineering modifications and intelligent response designs.
Immunotherapy has emerged as a promising strategy for combating tumor metastasis and recurrence, however, its efficacy is often hampered by the immunosuppressive tumor microenvironment (TME). The integration of nanomedicine-based photothermal therapy (PTT) with immunotherapy offers great potential to reshape the immune landscape, thereby enhancing immune responses and therapeutic outcomes. Nevertheless, conventional hyperthermia may induce heat-related damage and excessive inflammation in normal tissues. To address this challenge, we developed a novel therapeutic platform that combines tumor-specific delivery of melittin (MLT) with mild PTT using two-dimensional palladium nanosheets (Pd NSs). This approach allows for selective accumulation of MLT at tumor sites via the enhanced permeability and retention (EPR) effect and TME-responsive release, thereby maximizing antitumor efficacy while minimizing off-target toxicity. The resulting nanocomposite, MLT@Pd@PEG, exhibits excellent biocompatibility and efficient photothermal conversion under 808 nm laser irradiation. The acidic pH and localized heat in the TME synergistically trigger the controlled release of MLT, which disrupts cancer cell membranes and promotes tumor cell apoptosis. Moreover, this treatment facilitates the release of tumor-associated antigens and danger-associated molecular patterns (DAMPs), thereby activating cytotoxic T lymphocytes and natural killer (NK) cells. In vivo studies demonstrate that the combination of immune checkpoint blockade and MLT@Pd@PEG not only eradicates primary and distant tumors in bilateral tumor-bearing mouse models but also prevents tumor recurrence and metastasis by inducing durable immune memory. This comprehensive strategy integrating precise MLT delivery with mild PTT holds significant promise for advancing next-generation cancer immunotherapy.
In the treatment of B-cell lymphoma, chemotherapy as a monotherapy encounters significant challenges like drug resistance, side effects, and limited cytotoxicity. A novel strategy combining chemotherapy and photothermal therapy uses nanomaterials to convert light into heat, locally heating tumor tissues to induce thermal ablation while enhancing the effectiveness of chemotherapeutic agents and reducing toxic side effects on normal cells. Here, we developed a multifunctional black phosphorus nanosheets (BP NSs) for chemo-photothermal synergistic therapy of lymphoma. BP NSs were synthesized from bulk black phosphorus crystal powders utilizing a modified liquid exfoliation technique and functionalized with polyethylene glycol (PEG) to improve stability. The PEGylated BP NSs were loaded with two chemotherapeutic agents, gemcitabine (Gem) and doxorubicin (DOX), forming GD-BP@PEG NSs. The nanosheets exhibit excellent physical stability, efficient photothermal conversion, and pH/near-infrared (NIR) dual-responsive drug release. In vitro cell experiments demonstrated that GD-BP@PEG NSs significantly increased cytotoxicity and apoptosis, especially with NIR laser irradiation. Furthermore, in vivo studies in A20 lymphoma-bearing BALB/c nude mice revealed GD-BP@PEG NSs passively accumulated with high concentrations at the tumor site, efficiently inhibiting lymphoma growth with minimal systemic toxicity, demonstrating significant advantages over single treatments of chemotherapy or photothermal therapy alone. In summary, this pH/NIR dual-triggered BP NSs system could serve as a promising nanoplatform for chemo-photothermal synergistic treatment of B-cell lymphoma.
The low tumor immunogenicity, high immunosuppressive microenvironment, and off-target toxicity severely limit the efficiency of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway that plays an important role in tumor immunotherapy. We herein develop a multifunctional nano-assembly with tumor targeting, double-stranded DNA (dsDNA) releasing, Mn2+ sensitizing and immune microenvironment reprogramming capabilities for improving cGAS-STING to bridge innate and adaptive immunity. The drug-free nano-assembly composed of organic AIE-type photosensitizer and MnO2 can improve the tumor immune microenvironment by consuming glutathione and producing oxygen in the presence of H2O2, concurrently enhancing the release of damaged dsDNA and sensitizing the cGAS by controlled release of Mn2+ to magnify cGAS-STING immunity. In vivo experiments reveal that the multi-mode synergistic activation of STING pathway at the headstream can not only damage the primary tumors to amplify innate immunity, but also facilitate the maturation of dendritic cells, infiltration of cytotoxic T lymphocytes and expansion of adaptive immunity to inhibit primary tumor metastasis and recurrence in the long term.
Chiral phthalides are present in numerous natural products and bioactive molecules. Synthesizing phthalides from alkenes is an effective strategy. However, the challenges of facial-selectivity in the addition to Z/E mixed alkenes and diastereoselectivity at vicinal stereogenic centers have prevented the achievement of a highly selective stereoconvergent synthesis of chiral sulfonyl phthalides from Z/E alkene mixtures. Therefore, we have developed an efficient methodology for the stereoconvergent synthesis of chiral sulfonyl phthalides, using the Cu/PyBim catalytic system. This method enables the asymmetric construction of sulfonyl phthalides with multiple stereocenters for the first time. It exhibits broad applicability across various terminal and internal alkene substrates, and accommodates a diverse array of aryl, alkyl, and nitrogen radical precursors, all under exceptionally mild reaction conditions. The experimental results indicate that the reaction utilizes a Curtin-Hammett kinetic control strategy, leading to the stereoconvergent synthesis of Z/E internal alkene substrates with significant enantioselectivity and diastereoselectivity in the asymmetric construction of chiral sulfonyl phthalides.
Fluoroorganic chemistry is one of the most hectic areas of current chemical research, exerting a profound effect on the most vital industries such as medicine, pesticide, and material science. Synthesis of fluorine-containing organic molecules, particularly those that bear C(sp3)−F bonds, remains a great challenge in modern chemical synthesis. Herein, we disclose a new strategy for the construction of a carbon−fluorine quaternary center, which was accomplished with the silver(Ⅰ)-catalyzed intramolecular Wagner−Meerwein rearrangement fluorination of allylic gem-disubstituted alkene derivatives by using a hypervalent monofluoroiodine(Ⅲ) reagent 1 (AFBI). Interestingly, the tunable five/six-membered heterocycle selectivity is achieved by the intramolecular Wagner−Meerwein rearrangement fluorination via a judicious choice of the group R1 attached to the C−C double bond. This versatile strategy features simple starting materials, mild reaction conditions, good functional-group compatibility, high bond-forming efficiency (e.g., one C−F and one C−O bond), and excellent chemoselectivity. The proposed reaction mechanisms and the roles of the catalyst AgBF4 were understood by control experiments and density functional theory calculations.
Macrocyclic cascade supramolecular assembly could significantly enhance the fluorescence/phosphorescence resonance energy transfer (F/PRET) efficiency through macrocyclic and spatial dual confinement effect. Herein, we reported a cascade supramolecular assembly containing 6-bromoisoquinolinium-modified permethylated cyclodextrin (BQ-PCD), cucurbit[7]uril (CB[7]), and tetra(4-sulfonatophenyl)porphyrin (TPPS), in which the enhanced PRET from 6-bromoisoquinolinium (BQ) to TPPS could be achieved through the dual macrocyclic confinement for multicolor delayed luminescence and information encryption. In TPPS$\subset$BQ-PCD$\subset$CB[7], pure organic room temperature phosphorescence of BQ-PCD at 530 nm is induced by CB[7] macrocyclic confinement, which further transferred to TPPS via spatial confinement, achieving delayed fluorescence at 645 and 715 nm with high PRET efficiency and quantum yield (17.9%). Meanwhile, reversible TPPS concentration-dependent multicolor luminescence was achieved in presence of competitive guest (methionine peptide), followed by porphyrin-photosensitization process, being applied in information encryption. This research presents a facile strategy for efficient PRET through macrocyclic cascade confinement assembly.
The fabrication of three-component supramolecular organic frameworks (SOFs) is a considerable difficulty owing to the intricate noncovalent interactions and the constraints of current synthesis techniques. In this study, we designed and synthesized two photosensitive modules: a naphthalene-modified triphenylamine derivative (NA-TPA) as the donor unit, and a trimethylated viologen-modified triphenylamine (MV-TPA) as the acceptor unit. These modules can self-assemble into a novel two-dimensional SOF via encapsulation-enhanced donor-acceptor interactions with cucurbit[8]uril (CB[8]) in the aqueous solution. The resulting donor-acceptor SOF forms stable two-dimensional nanosheet structures in water. Compared to the individual monomers NA-TPA and MV-TPA, the SOF enhances electron transfer and significantly improves the generation of superoxide anion radicals (O2•−), which in turn effectively promotes the photocatalytic cyclization reaction between o-phenylenediamine and benzaldehyde in water, achieving a yield of up to 94%. This work offers valuable insights into the design and construction of three-component SOFs based on encapsulation-enhanced donor-acceptor interactions for photocatalytic applications.
The generation of transient radical species via carbon–metal bond homolysis is extremely useful, which can be harnessed to promote useful and selective radical-type transformations by the combination of transition metal catalysis. We herein establish a carbon–metal bond homolysis/recombination model for the formation of enantiomerically enriched carbon-metal species, which accounts for the Ni-catalyzed enantioconvergent carboxylation of racemic benzyl ammonium salts with CO2. Theoretical studies suggest a distinct pathway involving a stereoinvertive nucleophilic substitution-type oxidative addition of racemic benzyl ammonium salts to Ni(0), forming a racemic benzyl Ni(Ⅱ) intermediate. Subsequent C–Ni bond homolysis of one enantiomer enables the formation of a transient radical, followed by a dynamic rotation along C–C· bond and radical recombination forming another more thermodynamically favored enantiomer. Geometry analysis suggests less H–H repulsion between the benzyl group and chiral ligand in the more stable isomer. After the reduction and stereoretentive inner-sphere nucleophilic attack on CO2 process, the desired enantiomerically enriched carboxylic acid product is generated. ETS-NOCV analysis reveals a significant back-donation interaction between the dx2-y2 orbital of Ni atom and the unoccupied π* orbital of CO2 in inner-sphere transition state, thus effectively stabilizing the Ni–CO2 complex and facilitating subsequent C–C bond formation. The theoretical calculations provide critical insights into the systematic development of transition metal-catalyzed asymmetric carboxylation, highlighting significant potential for broad applications in synthetic organic chemistry.
Although C2-symmetric C–C atropisomeric diphosphines such as BINAP and SEGPHOS, have achieved tremendous success in enantioselective catalysis in recent centuries, developing diphosphines based on new structural scaffolds is still highly desirable. Here, C2-symmetric N–N atropisomeric diphosphines have been synthesized and comprehensively analyzed. These diphosphines exhibit excellent substituent-dependent tunable dihedral angles comparable to other useful electron-enriched diphosphines. With the aid of these newly developed diphosphines, the transition-metal catalyzed enantioselective dearomatization of heteroaryls is carried out to yield final products with excellent enantioselectivities, indicating their exceptional stereoinduction abilities.
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