Advanced Nanobiomed Research最新文献

Nanomedicine shows remarkable potential to improve the efficacy of diagnosis and treatment of tumors, utilizing nanotechnologies and nanomaterials. Gold nanoclusters (AuNCs) have emerged as a highly promising option due to their exceptional optical and enzyme-mimicking catalytic activities as well as good biocompatibility. The renal clearable clusters can enrich in the tumors upon their enhanced permeability and retention properties, which benefits the tumor-related applications. The fluorescence of AuNCs in the second near-infrared region possesses extraordinary penetration depth and high temporal–spatial resolution, enabling excellent in vivo imaging and real-time monitoring of pathological process. AuNC-based nanoplatforms represent a paradigm of integrated, efficient, intelligent, and safe treatment strategy, extending personalized tumor therapy. Meanwhile, the optical and biocatalytic properties can be modulated by adopting the atom/ligand engineering, which further enhances the efficacy of AuNCs. Herein, the advances of AuNCs in the field of diagnosis and treatment of tumors are summarized and the directions to be improved are proposed to promote the clinical translation of the AuNCs.

Despite remarkable advances in understanding the mechanisms underlying inflammation, the currently available anti-inflammatory therapies have many limitations, such as poor efficacies, low selectivity, and severe adverse effects. Bioactive materials with intrinsically anti-inflammatory activities have emerged as promising drug candidates for the treatment of inflammatory disorders. Among them, nanotherapies based on bioactive cyclodextrin (CD) materials have attracted much attention, owing to their multiple advantages, including broad availability, well-controlled structures, easy functionalization, good processibility, high cost-effectiveness, and excellent biocompatibility. This review provides a comprehensive overview of the recent advancements in the development and applications of anti-inflammatory nanoparticles (NPs) based on bioactive CD materials, with special focus on reactive oxygen species-scavenging NPs and NPs capable of regulating inflammatory cell recruitment and activation. In addition, the applications of these anti-inflammatory nanotherapies in the treatment of different acute/chronic inflammatory diseases are highlighted. Furthermore, major challenges in the clinical translation of these new generation anti-inflammatory therapies derived from bioactive CD materials are discussed.

Age-related macular degeneration (AMD), the leading cause of vision loss among older individuals, is characterized by damage to photoreceptors and retinal pigment epithelial cells (RPEs). Oxidative stress and chronic inflammation in the retina play notable roles in AMD pathogenesis, rendering them attractive therapeutic targets. Cerium oxide nanoparticles (CeNPs) have shown promise in scavenging reactive oxygen species (ROS) by mimicking antioxidant enzymes, whereas mesoporous materials have emerged as versatile drug carriers. Herein, mesoporous CeNPs (mCeNPs) that integrate the advantages of CeNPs and mesoporous materials are presented. The mCeNPs can be synthesized using 1,1′-carbonyldiimidazole and imidazole in acetone without heating and pressurization. The resulting mCeNPs exhibit mesoporous structures comprising assembled small CeNPs, exerting excellent ROS-scavenging capabilities, biocompatibility, and cytoprotective and anti-inflammatory effects against H₂O₂-induced damage in RPEs. Using a sodium iodate-induced AMD mouse model, it is demonstrated that intravitreal mCeNP administration can exhibit disease-preventive effects. These findings indicate the therapeutic potential of mCeNPs against AMD.

DNA Detection

DNA chips have transformed point-of-care diagnostics, offering rapid, precise genetic data detection. Integrated into lab-on-a-chip setups, they facilitate cost-effective, portable testing. In article number 2300058, Nadnudda Rodthongkum, Orawon Chailapakul, Kwanwoo Shin, and co-workers discuss recent rapid diagnostic DNA chip platforms, probe selection, and detection methods, emphasizing their potential to enhance patient outcomes and disease management.

Human neuraminidase-1 (NEU1) plays a much more profound function in human cancers than previously considered. It is demonstrated that cancer cell surface NEU1 is a desired gatekeeper for an innovative anticancer therapeutic nanomedicine enabling active drug-targeting delivery by specific endocytosis into the cytoplasm. Nanosome, an antiadhesive nanoparticular shuttle, carrying multiple suicide substrates for NEU1 confers potent and universal inhibitory effects on the proliferation of human cancer cells, such as hepatocellular carcinoma (HCC) (HepG2, IC₅₀ = 13.5 nM), lung cancer (A549, IC₅₀ = 9.57 nM), and colon cancer (HT-29, IC₅₀ = 11.1 nM), in which irreversible inactivation of cell surface NEU1 is essential for the intracellular trafficking and subsequent lysosomal membrane permeabilization by nanosomal aggregation due to the formation of “sialidase corona” through irreversible inactivation of NEU1–NEU4 residing in lysosome. Nanomedicine targeting membrane-tethered NEU1 allows efficient delivery of hydrophobic sorafenib (Nexavar), a RAF family kinase inhibitor for the treatment of advanced renal cell carcinoma and unresectable HCC at the recommended dose of 400 mg orally twice daily, into endolysosome, resulting in a potent and sustainable inhibition (IC₅₀ = 3.1–6.2 nM at 24–96 h after coincubation) against HepG2 cell growth.

Injectable Nanoparticles

Appropriate materials for the efficient and selective capturing of plasma cytokines are urgently needed. In article number 2300037, Jianliang Shen, Xuewu Liu, and co-workers design injectable porous silicon particles (PSPs) as scavenging adsorbents. The fabricated PSPs feature high porosity for large pore volume and high specific surface area, and a longer body circulation time. To facilitate specific recognition of targeting biomacromolecules, antibodies are immobilized on the interior surface of the PSPs.

DNA chips play a crucial role in point-of-care diagnostics by enabling rapid and accurate detection of genetic information. These chips offer high sensitivity and selectivity, allowing for the identification of specific DNA sequences associated with diseases and pathogens. Integration into lab-on-chip platforms streamlines and miniaturizes diagnostic workflows, paving the way for cost-effective, portable, and user-friendly testing devices that can revolutionize healthcare delivery. In this review, a comprehensive description of the platforms utilized in DNA analysis, including microfluidic devices and integrated DNA chips, is provided. It explores the selection and immobilization of DNA probes for improved selectivity. Additionally, it covers diverse detection techniques such as optical detection (colorimetry and fluorescence) and electrochemical techniques. In these discussions, it is aimed to provide a thorough understanding of the current state of the art in DNA biosensor-integrated lab-on-chip technology for point-of-care testing. The continued advancements in DNA chip technology hold immense promise for the development of next-generation point-of-care diagnostics, where integrated sample preparation and rapid results generation can further enhance patient outcomes and contribute to the effective management of diseases.

Bombyx mori silk fibroin is a natural biomacromolecule that can be assembled into nanoparticles. Manganese dioxide (MnO₂) is responsive to tumor microenvironment (TME). Herein, SF and MnO₂ is integrated to develop novel TME-responsive drug carriers. Specifically, silk fibroin nanoparticles (SF-NPs) are used as a biotemplates to regulate the nucleation and self-assembly of MnO₂ for designing the complex drug delivery (SM-NPs). The SM-NPs are further modified by polyethylene glycol and folic acid to improve their stability and tumor targeting. The resultant nanocarriers (SMPF-NPs) present a raspberry-like structure with lamellar MnO₂ nanoparticles coating on its surface. The SMPF-NPs show a high drug-loading capability and selectively release drugs in acidic TME. Due to the catalytic activity of MnO₂, the SMPF-NPs generate high levels of oxygen under H₂O₂ and produce more reactive oxygen after loading Ce6. In vivo and in vitro analysis prove that SMPF-NPs can accumulate in breast tumor tissues, efficiently kill cancer cells, and destroy breast cancer tumors by a combination of chemotherapy and photodynamic therapy (PDT). Moreover, the SMPF-NPs also provide fluorescence and magnetic resonance (MR) imaging for guiding cancer therapy. These results suggest that the self-assembled SF and MnO₂ nanocomplex could be a novel TME-responsive nanodrug delivery system.

Successful engineering of functional salivary glands necessitates the creation of cell-instructive environments for ex vivo expansion and lineage specification of primary human salivary gland stem cells (hS/PCs). Herein, basement membrane mimetic hydrogels are prepared using hyaluronic acid, cell adhesive peptides, and hyperbranched polyglycerol (HPG), with or without sulfate groups, to produce “hyperGel+” or “hyperGel”, respectively. Differential scanning fluorescence experiments confirm the ability of the sulfated HPG precursor to stabilize fibroblast growth factor 10. The hydrogels are nanoporous, cytocompatible, and cell-permissive, enabling the development of multicellular hS/PC spheroids in 14 days. The incorporation of sulfated HPG species in the hydrogel enhances cell proliferation. Culture of hS/PCs in hyperGel+ in the presence of a Rho kinase inhibitor Y-27632 (Y-27) leads to the development of spheroids with a central lumen, increases the expression of acinar marker aquaporin-3 at the transcript level (AQP3), and decreases the expression of ductal marker keratin 7 at both the transcript (KRT7) and the protein levels (K7). Reduced expression of transforming growth factor beta (TGF-β) targets SMAD2/3 is also observed in Y27-treated cultures, suggesting attenuation of TGF-β signaling. Thus, hyperGel+ cooperates with the Rho-associated protein kinase inhibitor to promote the development of lumened spheroids with enhanced expression of acinar markers.

Cancer is one of the leading causes of high mortality worldwide, affecting most of the body organs including the breast and colon. Triple-negative breast (TNBC) and colorectal cancers (CRC) usually present the poorest clinical outcomes and lowest disease-free survival rates among the different cancer types. Novel biomarkers for early detection of TNBC and CRC have been proposed throughout the years, although the rate of success remains limited. Herein, a dual method for detection of cancer-derived exosomes based on the measurement of the Raman spectra in graphene field-effect transistors (GFETs) is proposed, thereby obtaining electrical signal metrics related to the variation of the Dirac point in graphene and optical features corresponding to representative bio-molecular cancer structures in an orthogonal way. This pioneering method and classification routine can potentially be extended to other types of cancer, thus creating a unique and universal tag-free diagnostic template for early cancer diagnostics.