Surface Nanopore Engineering of 2D MXenes for Targeted and Synergistic Multitherapies of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and deadly gastrointestinal malignancies. Given its insensitivity to traditional systematic chemotherapy, new therapeutic strategies for efficient HCCs treatment are urgently needed. Here, the development of a novel 2D MXene‐based composite nanoplatform for highly efficient and synergistic chemotherapy and photothermal hyperthermia against HCC is reported. A surface‐nanopore engineering strategy is developed for the MXenes’ surface functionalization, which achieves the uniform coating of a thin mesoporous‐silica layer onto the surface of 2D Ti₃C₂ MXene (Ti₃C₂@mMSNs). This strategy endows MXenes with well‐defined mesopores for on‐demand drug release/delivery, enhanced hydrophilicity/dispersity, and abundant surface chemistry for targeting engineering. Systematic in vitro and in vivo evaluations have demonstrated the high active‐targeting capability of arginine‐glycine‐aspartic acid (RGD)‐targeting Ti₃C₂@mMSNs into tumor, and the synergistic chemotherapy (contributed by the mesoporous shell) and photothermal hyperthermia (contributed by the Ti₃C₂ MXene core) completely eradicate the tumor without obvious reoccurrence. This work not only provides a novel strategy for efficiently combating HCC by developing MXene‐based composite nanoplatforms, but also paves a new way for extending the biomedical applications of MXenes by surface‐nanopore engineering.     

Protonation‐Assisted Exfoliation of N‐Containing 2D Conjugated Polymers

Ultrathin 2D conjugated polymer nanosheets are an emerging class of photocatalysts for solar‐to‐chemical energy conversion. Until now, the majority of ultrathin 2D polymer photocatalysts are produced through exfoliation of layered polymers. Unfortunately, it still remains a great challenge to exfoliate layered polymers into ultrathin nanosheets with high yields. In this work, a liquid‐phase protonation‐assisted exfoliation is demonstrated to enable remarkably improved exfoliation yields of various 2D N‐containing conjugated polymers such as g‐C₃N₄, C₂N, and aza‐CMP. The exfoliation yields are only 2–15% in pure water whereas they can be substantially improved to 41–56% in 12 m HCl. The exfoliated ultrathin nanosheets possess average thicknesses less than 5 nm and can be easily dispersed in aqueous solutions. More importantly, the exfoliated nanosheets exhibit significantly enhanced photocatalytic activity toward photocatalytic water splitting compared to their bulk counterparts. Further characterizations and computational calculations reveal that protonation of the heterocyclic nitrogen sites in the conjugated polymer frameworks can lead to strong hydrogen bonding between the polymer surfaces and water molecules, resulting in facilitated exfoliation of polymers into the liquid phase. This study unveils an important protocol toward producing ultrathin 2D N‐containing conjugated polymer nanosheets for future solar energy conversion.     

Mechanical Exfoliation of Select MAX Phases and Mo4Ce4Al7C3 Single Crystals to Produce MAXenes

MXenes—2D carbides/nitrides derived from their bulk nanolamellar M_n+1AX_n phase (MAX) counterparts—are, for the most part, obtained by chemical etching. Despite the fact that the M? A bonds in the MAX phases are not weak, in this work it is demonstrated that relatively large MAX single crystals can be mechanically exfoliated using the adhesive tape method to produce flakes whose thickness can be reduced down to half a unit cell. The exfoliated flakes, transferred onto SiO₂/Si substrates, are analyzed using electric force microscopy (EFM). No appreciable variation in EFM signal with flake thickness is found. EFM contrast between the flakes and SiO₂ not only depends on the contact surface potential, but also on the local capacitance. The contribution of the latter can be used to show the metallic character—confirmed by four‐contact resistivity measurements—of even the thinnest of flakes. Because the A‐layers are preserved, strictly speaking MXenes are not dealt with in this work, but rather MAXenes. This is important in the case where the “A” layers contain magnetic elements such as Mo₄Ce₄Al₇C₃, whose structure is a derivative of the MAX structure.     

Metabolizable Ultrathin Bi2Se3 Nanosheets in Imaging‐Guided Photothermal Therapy

Poly(vinylpyrrolidone)‐encapsulated Bi₂Se₃ nanosheets with a thickness of 1.7 nm and diameter of 31.4 nm are prepared by a solution method. Possessing an extinction coefficient of 11.5 L g^?1 cm^?1 at 808 nm, the ultrathin Bi₂Se₃ nanosheets boast a high photothermal conversion efficiency of 34.6% and excellent photoacoustic performance. After systemic administration, the Bi₂Se₃ nanosheets with the proper size and surface properties accumulate passively in tumors enabling efficient photoacoustic imaging of the entire tumors to facilitate photothermal cancer therapy. In vivo biodistribution studies reveal that they are expelled from the body efficiently after 30 d. The ultrathin Bi₂Se₃ nanosheets have large clinical potential as metabolizable near‐infrared‐triggered theranostic agents.     

Wet/Sono‐Chemical Synthesis of Enzymatic Two‐Dimensional MnO2 Nanosheets for Synergistic Catalysis‐Enhanced Phototheranostics

2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug‐loading capacity, and excellent photothermal conversion. However, few studies report their “enzyme‐like” catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one‐step wet‐chemical method is first proposed for protein‐directed synthesis of 2D MnO₂ nanosheets (M‐NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono‐chemical approach is introduced for surface functionalization of the M‐NSs with high dispersity/stability as well as metal‐cation‐chelating capacity, which can not only chelate ⁶⁴Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn²⁺ for enhanced biosafety. Interestingly, the resulting M‐NS exhibits excellent enzyme‐like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well‐designed M‐NS can achieve effective photoacoustic‐imaging‐guided synergistic starvation‐enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small‐sized and ultrathin M‐NSs, which will broaden the application of 2D nanomaterials.     

Sub‐10‐nm Pd Nanosheets with Renal Clearance for Efficient Near‐Infrared Photothermal Cancer Therapy

Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra‐small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra‐small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface‐functionalized with reduced glutathione (GSH), the SPNS‐GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra‐small Pd nanosheets promising for practical use in photothermal cancer therapy.     

25th Anniversary Article: MXenes: A New Family of Two‐Dimensional Materials

Recently a new, large family of two‐dimensional (2D) early transition metal carbides and carbonitrides, called MXenes, was discovered. MXenes are produced by selective etching of the A element from the MAX phases, which are metallically conductive, layered solids connected by strong metallic, ionic, and covalent bonds, such as Ti₂AlC, Ti₃AlC₂, and Ta₄AlC₃. MXenes ­combine the metallic conductivity of transition metal carbides with the hydrophilic nature of their hydroxyl or oxygen terminated surfaces. In essence, they behave as “conductive clays”. This article reviews progress—both ­experimental and theoretical—on their synthesis, structure, properties, intercalation, delamination, and potential applications. MXenes are expected to be good candidates for a host of applications. They have already shown promising performance in electrochemical energy storage systems. A detailed outlook for future research on MXenes is also presented.     

The effect of the interlayer element on the exfoliation of layered Mo2AC (A = Al,Si, P,Ga, Ge,As or In) MAX phases into two-dimensional Mo2C nanosheets

The experimental exfoliation of layered, ternary transition-metal carbide and nitride compounds, known as MAX phases, into two-dimensional (2D) nanosheets, is a great development in the synthesis of novel low-dimensional inorganic systems. Among the MAX phases, Mo-containing ones might be considered as the source for obtaining Mo₂C nanosheets with potentially unique properties, if they could be exfoliated. Here, by using a set of first-principles calculations, we discuss the effect of the interlayer ‘A’ element on the exfoliation of Mo₂AC (A = Al, Si, P, Ga, Ge, As or In) MAX phases into the 2D Mo₂C nanosheets. Based on the calculated exfoliation energies and the elastic constants, we propose that Mo₂InC with the lowest exfoliation energy and the highest elastic constant anisotropy between C₁₁ and C₃₃ might be a suitable compound for exfoliation into 2D Mo₂C nanosheets.     

Ternary Chalcogenide Nanosheets with Ultrahigh Photothermal Conversion Efficiency for Photoacoustic Theranostics

2D materials (TDMs) have been explored for photonic theranostics. To achieve deep‐tissue penetration, near‐infrared (NIR) light is essential for photoacoustic (PA) theranostics. However, because the absorption profiles of existing TDMs are generally featureless with no obvious NIR absorption peaks, their PA signals and therapeutic efficacies are limited. This paper herein reports the synthesis and application of ternary chalcogenide nanosheets (Ta₂NiS₅‐P) for PA theranostics. In contrast to the current TDMs for such application, Ta₂NiS₅‐P has a ternary instead of binary composition. This difference brings in the strong and featured NIR for Ta₂NiS₅‐P. To the best of the knowledge, this is the first example using ternary chalcogenide nanosheets for such application; moreover, the photothermal conversion efficiency of Ta₂NiS₅‐P is the highest (35%) among all the reported TDMs based on the same calculation method. These advantages allow Ta₂NiS₅‐P to passively target, effectively delineate, and completely eradicate the tumor of living mice after systemic administration.     

Coupling PtNi Ultrathin Nanowires with MXenes for Boosting Electrocatalytic Hydrogen Evolution in Both Acidic and Alkaline Solutions

Developing an efficient electrocatalyst for the hydrogen evolution reaction (HER) working in both acidic and alkaline solutions is highly desirable, but still remains challenging. Here, Pt_xNi ultrathin nanowires (NWs) with tunable compositions (x = 1.42, 3.21, 5.67) are in situ grown on MXenes (Ti₃C₂ nanosheets), serving as electrocatalysts toward HER. Such Pt_xNi@Ti₃C₂ electrocatalysts exhibit excellent HER performance in both acidic and alkaline solutions, with the Pt_3.21Ni@Ti₃C₂ being the best one. Specifically, Pt_3.21Ni@Ti₃C₂ achieves record‐breaking performance in terms of lowest overpotential (18.55 mV) and smallest Tafel slope (13.37 mV dec^?1) for HER in acidic media to date. Theory calculations and X‐ray photoelectron spectroscopy analyses demonstrate that the coupling of MXenes with the NWs not only approaches the Gibbs free energy for hydrogen adsorption close to zero through the electron transfer between them in acidic media, but also provides additional active sites for water dissociation in alkaline solution, both of them being beneficial to the HER performance.