Latest ArticlesEssential amino acids (EAAs) deprivation is a potential antitumor approach because EAAs are critical for tumor growth. To efficiently inhibit tumor growth, continuous deprivation of EAAs is required, however, continuous deprivation without precise control will introduce toxicity to normal cells. Herein, a programmable double-unlock nanocomplex (ROCK) was prepared, which could self-supply phenylalanine ammonia-lyase (PAL) to tumor cells for phenylalanine (Phe) deprivation. ROCK was double-locked in physiological conditions when administered systemically. While ROCK actively targeted to tumor cells by integrin αvβ3/5 and CD44, ROCK was firstly unlocked by cleavage of protease on tumor cell membrane, exposing CendR and R8 to enhance endocytosis. Then, hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells, in which ROCK was secondly unlocked, resulting in promoting endo/lysosome escape and PAL plasmid (pPAL) release. Released pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe, thereby blocking the protein synthesis and killing tumor cells specifically. Overall, our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells, providing new insights to efficiently remove intratumoral nutrition for cancer therapy.
The monkeypox virus (MPXV) outbreak, declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in 2022, continues to pose a significant threat due to the absence of vaccines or drugs for MPXV infection. In this study, we developed an mRNA vaccine that expressing the A29L antigen, a specific protein of the intracellular mature virus. Our vaccine utilizes a thermostable ionizable lipid nanoparticle (iLNP) platform and has been administered to mice. Our findings demonstrate that the MPXV A29L mRNA vaccine candidate induces robust cross-neutralizing immune responses against both vaccinia virus (VACV) and MPXV live virus. Furthermore, immunization with the vaccine candidate provided protection against the VACV challenge in mice. These findings underscore the potential of mRNA-LNP vaccines as safe and effective candidates against monkeypox epidemics. Given the current absence of specific interventions for MPXV infection, our study represents a significant step forward in developing a viable solution to combat this ongoing public health threat.
Transition-metal-catalyzed remote sp2C—H functionalization of aryl sulfonic acids was hardly ever realized owing to competitive ortho-C—H functionalization of aryl sulfonates and electron-deficient nature of phenyl ring. Herein, with the assistance of a practical biaryl indolyl directing template, palladium-catalyzed remote sp2C—H alkylation of aryl sulfonic acids have been achieved in moderate to good yields with exclusive meta selectivity. Moreover, remote meta-selective C—H alkynylation of aryl sulfonic acids was also accomplished with a rhodium catalyst. These meta-C—H functionalized products proved to be the superior synthetic precursors, which are difficult to access using the conventional strategy.
Delayed or non-healing of diabetic wounds is a significant complication, often attributed to high glucose-induced M1 macrophage accumulation, impaired angiogenesis, and reactive oxygen species (ROS) buildup. Addressing this, we introduced a strontium polyphenol network microneedle patch (SrC-MPNs@MN-PP) for percutaneous drug delivery. This patch, formulated with polymer poly(γ-glutamic acid) (γ-PGA) and epsilon-poly-L-lysine (ε-PLL), incorporates strontium polyphenol networks (SrC-MPNs). The release of chlorogenic acid (CGA) from SrC-MPNs not only neutralizes ROS, but strontium ions also foster angiogenesis. Consequently, SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.
Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer cells. However, the conventional ATP biosensing strategy is often limited by the undesired on-target off-tumor interference. Here, we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes (En-DT) for biosensing and imaging ATP in tumor cells. The En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA tetrahedron. The En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1 (APE1) in cancer cells, but they did not respond to ATP in normal cells, thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor specificity. This strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.
The isolation of circulating tumor cells (CTCs) from complex biological samples is of paramount significance for advancing cancer diagnosis, prognosis, and treatment. However, the low concentration of CTCs and nonspecific adhesion of white blood cells (WBCs) present challenges that hinder the efficiency and purity of captured CTCs. Microfluidic-based strategies utilize precise fluid control at the micron level to incorporate specific micro/nanostructures or recognition molecules, enabling effective CTCs separation. Moreover, by employing surface modification designs that exhibit exceptional anti-adhesion properties against WBCs, the purity of isolated CTCs can be further enhanced. This review offers an in-depth exploration of recent advancements, challenges, and opportunities associated with microfluidic-based CTCs isolation from biological samples. Firstly, we will comprehensively introduce the microfluidic-based strategies for achieving high-efficiency CTCs isolation, which includes the morphological design of microchannels for physical force-based CTCs isolation and the specific modification of microchannel surfaces for affinity-based CTCs isolation. Subsequently, a review of recent research advances in microfluidic-based high-purity CTCs isolation is presented, focusing on strategies that decrease the nonspecific adhesion of WBCs through surface micro-/nanostructure construction or chemical and biological modification. Finally, we will summarize the article by providing the prospective opportunities and challenges for the future development of microfluidic-based CTCs isolation.
Electrocatalytic synthesis of urea through CN bond formation, converting carbon dioxide (CO2) and nitrate (NO3–), presents a promising, less energy-intensive alternative to industrial urea production process. In this communication, we report the application of Mo2C nanosheets-decorated carbon sheets (Mo2C/C) as a highly efficient electrocatalyst for facilitating CN coupling in ambient urea electrosynthesis. In CO2-saturated 0.2 mol/L Na2SO4 solution containing 0.05 mol/L NO3–, the Mo2C/C catalyst achieves an impressive urea yield of 579.13 µg h–1 mg–1 with high Faradaic efficiency of 44.80% at –0.5 V versus the reversible hydrogen electrode. Further theoretical calculations reveal that the multiple Mo active sites enhance the formation of *CO and *NH2 intermediates and facilitate their CN coupling. This research propels the use of Mo2C-based electrodes in electrocatalysis and accentuates the capabilities of binary metal-based catalysts in CN coupling reactions.
Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components, good biocompatibility, and high targeting. However, their large relative molecular weight, complex structure, susceptibility to degradation, and poor stability limit their usefulness. Nanotechnology can address these issues by improving the therapeutic value, bioavailability, permeability, and absorption of biomacromolecules while regulating their retention time in the body. Especially, compelling evidence has been reported that supercritical fluid (SCF) technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental contamination. In this review, we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine, and extensively discuss their characteristics and mechanisms. In particular, the protein-based, nucleic acid-based, and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized, and the potential for industrial production of biomacromolecular drugs is also considered. We further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.
Constructing composited electrode material is considered to be an efficient strategy to improve their electrochemical performance. It can accelerate the charge transfer speed of ions and enhance the conductivity of electrode. Meanwhile, the formation of the hybrid structure can largely avoid the aggregation of two dimensional materials and increase the electrochemical active area of the electrode. In this work, we synthesize NiMoSSe electrode materials on nickel foam by a facile hydrothermal avenue. The prepared composite shows a specific capacitance of 1035 C/g at 1 A/g due to the synergistic effect between MoS2 and MoSe2 phases. In addition, the devices are assembled with NiMoSSe samples, which offers an energy density of 82.71 Wh/kg at a power density of 2700 W/kg.
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