Latest ArticlesNanoparticles that employ stimuli-responsive polymeric delivery carriers have emerged as intelligent nanoplatforms with great potential in cancer theranostics, mainly including cancer diagnosis, controlled/triggered drug delivery, and real-time monitoring of therapeutic response. Particularly, tumor microenvironment (TME)-responsive polymeric nanocarriers in response to weak acidity, hypoxia, reactive oxygen species (ROS), glutathione (GSH), or tumor enzymes in the TME show great promise in facilitating tumor accumulation, enhancing tumor penetration, prolonging tumor retention, and achieving controlled drug release, thereby improving the efficiency of tumor therapy. Besides, the combination of chemotherapy and phototherapy presents a promising endeavor for the treatment of tumors, which allows for the integration of the advantages of each treatment modality, addressing the shortcomings of the two methods, and amplifying the efficacy of tumor treatment while reducing adverse reactions. This review focuses on the latest progress in the development of TME-responsive polymeric nanoparticles for synergetic chemo-photo therapy, and discusses the critical challenges and future considerations involved in the fabrication of TME-responsive nanocarriers.
Skin wound healing is an important aspect of regenerative medicine. Metal-organic frameworks (MOFs) have attracted considerable attention as promising nanomaterials for skin wound healing due to their remarkable versatility, tunable pore size, surface area, targeted delivery of various therapeutic agents, and controlled release properties. The combination of these materials with biocompatible and synthetic polymers can help improve their performance in wound regeneration. This review examines the potential of MOF-polymer composites in skin wound healing. Physical and biological chemical properties and methods of making MOFs and their composites have been investigated. In the final section of this review, challenges and future prospects for the development of MOF-polymer composites are stated.
Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is the most promising target for diabetes treatment by promoting β-cell proliferation. The desmethylbellidifolin (DMB) as a DYRK1A inhibitor could facilitate β-cell proliferation in vivo and in vitro. However, DMB has the problem of weak binding affinity to DYRK1A, which means that continuous high concentration administration of DMB is effective for the diabetes. In order to solve this problem, we designed and synthesized a series of DMB-based proteolysis targeting chimeras (PROTACs) by taking advantage of the property of PROTAC that induce protein degradation in a cycle-catalytic manner. MDM2-based PROTAC X1–4P-MDM2 was identified as the most active PROTAC molecule. Mechanism research showed that X1–4P-MDM2 formed a ternary complex with DYRK1A and murine double minute 2 (MDM2), and induced the degradation of DYRK1A through the ubiquitin-proteasome system pathway. At a dose much lower than that of DMB, X1–4P-MDM2 still significantly enhanced β-cell proliferation by inhibiting transforming growth factor beta (TGF-β) and promoting the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway, which may provide a new strategy for the application of DMB in diabetes.
The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable, but remain a big challenge. Herein, we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization, enabling the efficient synthesis of structurally diverse enantioenriched macrocycles. This robust enantioselective C-H macrocyclization has a broad functional group tolerance, excellent enantioselectivities (up to 98.5:1.5 e.r.) and a mild reaction condition, releasing CO2 as the single by-product. More significantly, the resulting unique enantioenriched 19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus (ZIKV) activity without obvious cytotoxicity. Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.
With the increasing demand for personalized and precise treatment, the rapid advancement of synthetic biology technology has inevitably led to the development of nanobiology-based drug delivery systems. Synthetic biology-based drug delivery systems are being increasingly used in the treatment of various diseases. On one hand, synthetic biology technology enables the clever combination of chassis cells, bacteria, and their derivatives with nanomaterials, forming nano-artificial hybrid systems. These systems effectively integrate the functions of both materials, leading to further breakthroughs and optimization of biological functions. On the other hand, synthetic biology strategies guide the self-assembly of modular nanocomponents with biocatalytic or intelligent response functions, resulting in the mimicry of living cell features such as compartmentalization of enzymatic reactions and responsiveness to external stimuli. This provides novel design ideas for the construction of artificial cells. This paper aims to explore the construction and application of biogenic drug delivery systems based on whole cells, cell membrane-encapsulated nanoparticles, exosomes, bacteria, bacterial outer membrane vesicles and artificial cells, taking into account recent advances in this field. The advantages and limitations of current synthetic biology-based nanodrug delivery systems for clinical translation are discussed, and the future prospects of nanotechnology for intelligent drug diagnostic and therapeutic systems are envisioned.
For the first time, proteolysis-targeting chimeras (PROTAC) technology was utilized to achieve the isoform-selective degradation of class Ⅰ phosphoinositide 3-kinases (PI3Ks) in this study. Through screening and optimization, the PROTAC molecule ZM-PI05 was identified as a selective degrader of p110α in multiple breast cancer cells. More importantly, the degrader can down-regulate p85 regulatory subunit simultaneously, thereby inhibiting the non-enzymatic functions of PI3K that are independent on p110 catalytic subunits. Therefore, compared with PI3K inhibitor copanlisib, ZM-PI05 displayed the stronger anti-proliferative activity on breast cancer cells. In brief, a selective and efficient PROTAC molecule was developed to induce the degradation of p110α and concurrent reduction of p85 proteins, providing a tool compound for the biological study of PI3K-α by blocking its enzymatic and non-enzymatic functions.
Enhancing the active tumor targeting ability and decreasing the clearance of reticuloendothelial system (RES) are important issues for drug delivery systems (DDSs) in cancer therapy. In recent years, cell membrane camouflage, as one of the biomimetic modification strategies, has shown huge potential. Many natural properties of source cells can be inherited, allowing the DDSs to successfully avoid phagocytosis by macrophages, prolong circulation time, and achieve homologous targeting to lesion tissue. In this study, a cancer cell membrane camouflaged nanoplatform based on gelatin with a typical core-shell structure was developed for cancer chemotherapy. Doxorubicin (DOX) loaded gelatin nanogel (NG@DOX) acted as the inner core, and 4T1 (mouse breast carcinoma cell) membrane was set as the outer shell (M-NG@DOX). The M-NG platform enhanced the ability of homologous targeting due to the surface protein of cell membrane being completely retained, which could promote the cell uptake of homotypic cells, avoid phagocytosis by RAW264.7 macrophages, and therefore increase accumulation in tumor tissue. Meanwhile, due to the better controlled drug release capability of M-NG@DOX, premature release of DOX in circulation could be reduced, minimizing side effects in common chemotherapy. As a result, the biomimetic nanoplatform in this study, obtained by a cancer cell membrane camouflaged drug delivery system, efficiently reached desirable tumor elimination, providing a significant strategy for effective targeted therapy and specific carcinoma therapy.
Developing natural nano-platforms with high biocompatibility and natural targeting ability represents great significance for drug delivery. High-density lipoprotein (HDL), a natural lipid-protein complex, plays important roles in physiological activities, particularly in reverse cholesterol transport (RCT) and be closely associated with atherosclerotic cardiovascular diseases. Recent studies have demonstrated that HDLs have the potential to serve as ideal drug carriers. Recombinant HDLs (rHDLs) have been used to encapsulate substances such as small interfering RNA (siRNA), drugs, and contrast agents, fully utilizing the biocompatibility and targeting ability of rHDL in the body and providing new strategies for drug delivery and disease treatment. In this review, we discussed in detail the basic principles of HDL as a drug delivery system, the mechanisms of targeted drug delivery, and several methods for preparing HDL nanoparticles. Afterward, we comprehensively reviewed the applications of HDL as a drug carrier in cardiovascular diseases, cancer treatment (such as glioblastoma, breast cancer, hepatocellular carcinoma and urologic cancers) and some other fields. Finally, we reviewed the therapeutic effects and safety of HDL nanoparticles in clinical studies. Through a review and summary of these research advances, we aim to fully understand the potential of HDL as a drug carrier in clinical applications, providing valuable references and guidance for future research and expedites the translational application of HDL as drug carriers.
Adenosine triphosphate (ATP), known as a common metabolic product in organism, is not only importance to provide energy in various cellular activities but also is widely explored in the bio-inspired synthetic supramolecular area which becomes a fascinating topic with the rapid development of biology, chemistry and materials science. In this review, the recent advances about ATP interacted with functional small organic compounds and metal coordinated complexes are summarized. The design principles, its function as an active supramolecular matrix, the associated non-covalent binding modes and assembly induced properties including the optical properties, morphologies are presented in details. Besides, their applications for metal ion detecting, enzyme activity monitoring and drug delivery are described due to their excellently dynamic assembly properties, adjustability, and response to stimuli. Finally, an overview of the existing challenges and future prospects of ATP-induced supramolecular systems are also discussed.
This article reviews the latest research advances of tetrahedral framework nucleic acid (tFNA)-based systems in their fabrication, modification, and the potential applications in biomedicine. TFNA arises from the synthesis of four single-stranded DNA chains. Each chain contains brief sequences that complement those found in the other three, culminating in the creation of a pyramid-shaped nanostructure of approximately 10 nanometers in size. The first generation of tFNA demonstrates inherent compatibility with biological systems and the ability to permeate cell membrane effectively. These attributes translate into remarkable capabilities for regulating various cellular biological processes, fostering tissue regeneration, and modulating immune responses. The subsequent evolution of tFNA introduces enhanced adaptability and a relatively higher degree of biological stability. This advancement encompasses structural modifications, such as the addition of functional domains at the vertices or side arms, integration of low molecular weight pharmaceuticals, and the implementation of diverse strategies aimed at reversing multi-drug resistance in tumor cells or microorganisms. These augmentations empower tFNA-based systems to be utilized in different scenarios, thus broadening their potential applications in various biomedical fields.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
