Long-term pharmacological intervention is essential for managing chronic diseases, yet continuous administration of antithrombotic agents often increases bleeding risk, posing a major clinical challenge. Here, we designed a multifunctional drug delivery platform composed of large-aperture mesoporous silica (Mas) coated with silk fibroin (SF) or sustained heparin sodium (HS) release. The well-defined mesoporous structure enables high drug loading, while the biocompatible SF coating regulates release kinetics, suppresses burst release, and prolongs therapeutic efficacy. This dual structural system enhances antithrombotic performance while mitigating hemorrhagic risk. In vitro studies demonstrated improved hemocompatibility and reduced cytotoxicity of SF-Mas/HS compared with free HS. In vivo thrombosis models further confirmed effective inhibition of thrombus formation without excessive bleeding. By integrating inorganic mesoporous carriers with natural protein coatings, SF-Mas/HS provides a safe and efficient strategy for long-term antithrombotic prevention, highlighting the potential of biomaterial-assisted delivery systems to balance efficacy and safety in chronic disease management.

OBJECTIVES:Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. This study aimed to elucidate the molecular pathways through which isoliquiritigenin (ISL), a natural chalcone compound derived from licorice and other plant roots, targets interferon regulatory factor 5 (IRF5) in TNBC. METHODS:TNBC cell lines were cultured and subjected to IRF5 knockdown using short hairpin RNA. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assays. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR) were employed to measure expression levels of IRF5, solute carrier family 7 member 5 (SLC7A5), and indoleamine 2,3-dioxygenase 1 (IDO1). Intracellular tryptophan and its metabolites were quantified using commercially available assay kits and high-performance liquid chromatography (HPLC). TNBC cells were treated with various concentrations of ISL to evaluate its effects on proliferation and tryptophan metabolism. RESULTS:IRF5 was highly expressed in TNBC cell lines. Silencing IRF5 significantly inhibited cellular proliferation and growth. Knockdown of IRF5 reduced the expression of SLC7A5 and IDO1, leading to decreased intracellular levels of tryptophan and its metabolites. ISL markedly suppressed TNBC cell proliferation and disrupted tryptophan metabolism in tumor cells. CONCLUSION:ISL may inhibit TNBC progression by downregulating IRF5 and interfering with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming, suggesting a potential therapeutic mechanism for TNBC treatment.

Due to the lack of targeting specificity, rapid clearance, and high toxicity associated with small molecule drugs in tumor treatment, the design of an effective drug delivery system is crucial. To better overcome physiological barriers and achieve prolonged tumor retention, nanoparticles (Fe 3 O 4 @SiO 2 @Au, termed FSA‐NPs), made of core–shell NPs (Fe 3 O 4 @SiO 2 ), consisting of a Fe 3 O 4 core and a mesoporous silica (SiO 2 ) shell, and with their surfaces decorated with gold NPs, are constructed. The FSA‐NPs have a size range of 60–80 nm and a mildly negative surface charge. The magnetic Fe 3 O 4 core imparts magnetic targeting capabilities to FSA‐NPs, while the high porosity of the mesoporous silica shell enables efficient drug loading. Additionally, the gold NPs can convert light into heat. As a result, after being internalized by A549 lung cancer cells, FSA‐NPs exhibit potent cytotoxic effects against the cancer cells under an applied magnetic field, making them a promising theranostic agent for integrated cancer diagnosis and therapy.

The detection of antibiotics is crucial for safeguarding the environment, ensuring food safety, and promoting human health. However, developing a rapid, convenient, low-cost, and sensitive method for antibiotic detection presents significant challenges. Herein, an aptamer-free biosensor was successfully constructed using upconversion nanoparticles (UCNPs) coated with silk fibroin (SF), based on Forster resonance energy transfer (FRET) and the charge-transfer effect, for detecting roxithromycin (RXM). A synergistic FRET efficiency was achieved by utilizing alizarin red and RXM complexes as energy acceptors, with UCNP as the energy donor, and immobilizing an ultrathin SF protein corona within 10 nm. The biosensor detects RXM in deionized water with high sensitivity primarily through monolayer adsorption, with a detection range of 1.0 nM-141.6 nM and a detection limit as low as 0.68 nM. The performance of this biosensor was compared with the ultra-performance liquid chromatographymass spectrometry (UPLC-MS/MS) method for detecting antibiotics in river water separately and a strong correlation between the two methods was observed. The biosensor exhibited long-term stability in aqueous solutions (up to 60 d) with no attenuation of fluorescence intensity. Furthermore, the biosensor's applicability extended to the highly sensitive detection of other antibiotics, such as azithromycin. This study introduces a low-cost, ecofriendly, and highly sensitive method for antibiotic detection, with broad potential for future applications in environmental, healthcare, and food-related fields.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Silica-based magnetic nanoparticles are designed to deliver siRNA to triple negative breast cancer cells. The cells are killed due to siRNA-induced apoptosis upon the magnetic field-enhanced efficient cellular uptake and endosome escape of siRNA.

Programmed cell death-ligand 1 (PD-L1) blockers have advanced immunotherapy, but their lack of tumour homing capability represents a substantial challenge. Here we show that genetically engineered filamentous phages can be used as tumour-targeting immunotherapeutic agents that reduce the side effects caused by untargeted delivery of PD-L1 blockers. Specifically, we improved biopanning to discover a peptide binding the extracellular domain of PD-L1 and another targeting both melanoma tissues and cancer cells. The two peptides were genetically fused to the sidewall protein and tip protein of fd phages, respectively. The intravenously injected phages homed to tumours and bound PD-L1 on cancer cells, effectively blocking PD-1/PD-L1 recognition to trigger targeted immunotherapy without body weight loss, organ abnormalities and haematological aberrations. The phages, cost-effectively replicated by bacteria, are cancer-targeting immunotherapeutic nanofibres that can be flexibly designed to target different cancer types and immune checkpoints. Phages are known as human-safe nanosized viruses that specifically infect bacteria. This work shows that non-lytic filamentous phages displaying a PD-L1-binding peptide and a melanoma-targeting peptide can efficiently target tumours and inhibit tumour growth by blocking the immune checkpoint.

Skin is an essential and the largest organ of the human body. The epidermis on areas of the finger and palm appears as a series of papillary ridges and depressed furrows, and the sweat pores are intensively located on the papillary ridges (Wilshire 1996). These volar areas of the skin possessing complex forms and patterns are known to display papillary (or friction) ridge skin. The morphology of the papillary ridge skin is a direct reflection of its function. The papillary ridges facilitate the hands to grip surfaces firmly, and the sweat pores allow the perspiration to excrete.

Thrombotic disease poses a significant threat to human health as it blocks blood vessels and leads to severe symptoms. Effective treatment requires targeted therapy and precise localization of the thrombus, but traditional drugs are limited in their targeting ability and ability to locate the thrombus. To overcome these issues, a nanoparticle capable of both thrombus targeting and computed tomography (CT) imaging is developed. Phage display technology is used to screen for the thrombus-targeting peptide termed GK, which is then linked to the surface of macroporous silica (Mp-SiO2) with a Bi core to create Mp-Bi@SiO2-GK. The large pores of Mp-Bi@SiO2-GK enable the transport of the drug Urokinase (UK), while the Bi core provides the capabilities of CT imaging and photothermal therapy. The Mp-Bi@SiO2-GK nanoparticles precisely target thrombi in mouse carotid arteries and locate them via CT imaging. Furthermore, the combination of Bi-enabled photothermal therapy and UK-induced chemotherapy enhance the thrombolysis efficiency. Treatment with Mp-Bi@SiO2-GK nanoparticles do not harm tissues/organs or affect liver/kidney metabolism. These results show that Mp-Bi@SiO2-GK exhibits precise thrombus targeting and efficient imaging/treatment capability, making it a promising tool for the diagnosis and treatment of thrombosis.

A novel UCNP-based aptasensor for rapid and ultrasensitive detection of Staphylococcus aureus by low-speed centrifugation, with the detecting range from 6.36 × 10 2 to 6.36 × 10 7 CFU mL −1 .

Nanodendrite particles (NDs) with densely branched structures and biomimetic architectures have exhibited great promise in tumor therapy owing to their prolonged in vivo circulation time and exceptional photothermal efficiency. Nevertheless, traditional NDs are deficient in terms of specific surface modification and targeting tumors, which restrict their potential for broader clinical applications. Here, we developed coronavirus-like gold NDs through a seed-mediated approach and using silk fibroin (SF) as a capping agent. Our results demonstrate that these NDs have a favorable drug-loading capacity (∼65.25%) and light-triggered release characteristics of doxorubicin hydrochloride (DOX). Additionally, NDs functionalized with specific probes exhibited exceptional surface-enhanced Raman scattering (SERS) characteristics, enabling high-sensitivity Raman imaging of unstained single cells. Moreover, these NDs allowed for real-time monitoring of endocytic NDs for over 24 ​h. Furthermore, ND@DOX conjugated with tumor-targeting peptides exhibited mild hyperthermia, minimal cytotoxicity, and effective targeting towards cancer cells in vitro, as well as responsiveness to the tumor microenvironment (TME) in vivo. These unique properties led to the highest level of synergistic tumor-killing efficiency when stimulated by a near-infrared (NIR) laser at 808 ​nm. Therefore, our virus-like ND functionalized with SF presents a novel type of nanocarrier that exhibits significant potential for synergistic applications in precision medicine.

Due to the complexity and heterogeneity of cancer, the clear and accurate tumor imaging and image‐guided multimodal synergistic therapy are highly in demand. Here, bismuth (Bi)‐based mesoporous‐silica‐coated nanoparticles (BMSNs) are successfully fabricated with the silica shell thickness being lower than the Bi nanoparticle diameter. Then, an MCF‐7 breast cancer‐targeting peptide (termed AR) is modified onto the surface of BMSNs. The obtained nanoparticles (BMSN‐AR) show a significantly higher loading of doxorubicin hydrochloride (DOX). The resultant BMSN‐AR‐DOX can agglomerate in the tumor site, enabling enhanced computed tomography (CT) imaging of the whole tumor. Under 808 nm near‐infrared (NIR) laser irradiation, the BMSN‐AR‐DOX also effectively converts light energy into thermal energy to achieve synergistic chemo‐photothermal therapy in vivo. The chemo‐photothermal combination therapy is found to be more effective than chemotherapy or photothermal therapy alone. This work demonstrates that tumor‐homing peptides can guide nanoparticles to tumors and allow the nanoparticles to enhance cancer imaging and photothermal/chemo combination therapy.

Targeted brain tumor therapy by nanoparticles (NPs) remains a daunting challenge due to the difficulty for NPs to go through the blood-brain barriers (BBB) and blood-brain tumor barriers (BBTB). In addition, Dactolisib (Dac) is an effective dual PI3K/mTOR inhibitor for cancer treatment. It was the first PI3K inhibitor to enter clinical trials but exhibited toxicity to normal tissues if not delivered to tumor sites by a tumor-targeting carrier. To explore Dac for glioblastoma (GBM) therapy while avoiding its toxicity, we devel-oped a new brain tumor-targeting drug delivery system self-assembled from zein, a cell membrane-penetrating amphiphilic protein originally present in corn. Specifically, the amphiphilicity of zein drove it to self-assemble into NPs that encapsulated Dac with high efficiency. RVG29, a 29-mer brain-targeting peptide, was chemically conjugated to zein constituting the NPs, forming Dac-encapsulated NPs (zein-RVG-Dac_NPs). In vitro assays were conducted to verify the capability of the NPs in penetrating BBB/BBTB, targeting GBM cancer cells and killing them. ELISA was employed to assess the expression of nicotinic acetylcholine receptors (nAChR) on the cancer cells to understand the mechanism of cancer cell membrane penetration by the NPs. The NPs were intravenously injected into orthotopic GBM mice models to demonstrate the brain tumor targeting as well as the effective GBM therapy due to the targeted delivery of Dac to brain tumors. The treated tumors were immunohistochemically analyzed to verify the tumor destruction. To confirm the biosafety of the NPs in treating GBM, we also histopathologically evaluated the major normal organs and chemically analyzed the blood biomarkers. We found that a combination of zein and RVG29 facilitated the zein-RVG-Dac_NPs to cross the BBB/BBTB and became uptaken by the GBM cells through the nAChR-mediated pathways, enabling the NPs to cross BBB/BBTB and deliver Dac selectively to GBM cells. Hence, administration of the NPs through tail veins significantly increased the accumulation of Dac in the orthotopic brain tumor of mice and effectively inhibited tumor growth. Neither toxicity nor adverse effects in the major organs were found due to the excellent biocompatibility of zein and the tar-geted delivery of Dac into brain tumor cells. Hence, integrating a cell-penetrating natural protein (zein) and a brain-targeting peptide (RVG29) can form NPs that can effectively penetrate BBB/BBTB and then enter brain tumor cells to release Dac, leading to highly effective targeted brain cancer therapy. Such NPs can be extended to the development of therapeutics for treating different brain diseases due to their unique combination of biocompatibility and brain-targeting capability.& COPY; 2023 Elsevier Ltd. All rights reserved.

Abstract Biological molecules such as DNA, proteins, and lipids can be assembled into naturally existing nanoparticles, such as bacterial viruses (also called bacteriophages or phages), plant viruses, nucleic acid nanoparticles (e.g., DNA origami), protein nanoparticles, and exosomes. These bionanoparticles have their own distinct properties (including compositions, structures, shapes, and functions), laying the foundation for their unique applications as probes for cancer imaging, as detectors for cancer diagnosis, or as therapeutics for cancer therapy. To highlight how the distinct properties of different bionanoparticles can be explored in cancer nanotheranostics, this review critically analyzed the use of bionanoparticles in cancer imaging, diagnosis, and treatment. Specifically, for each of these representative bionanoparticles, we describe its unique properties that render it powerful in cancer theranostics compared with synthetic inorganic nanoparticles. We also summarize how to genetically or chemically modify or redesign the bionanoparticles so that they gain new functions desired for cancer theranostics, such as tumor‐seeking or tumor‐destructive capabilities. Finally, we discussed the challenges in this exciting field. The bionanoparticles covered in this review represent different biomolecular assemblies with unique theranostic applications, showcasing the power of bionanoparticles in disease diagnosis and treatment.

Microorganisms have gained defense systems during the lengthy process of evolution over millions of years. Such defense systems can protect them from being attacked by invading species (e.g., CRISPR-Cas for establishing adaptive immune systems and nanopore-forming toxins as virulence factors) or enable them to adapt to different conditions (e.g., gas vesicles for achieving buoyancy control). These microorganism defense systems (MDS) have inspired the development of biosensors that have received much attention in a wide range of fields including life science research, food safety, and medical diagnosis. This Review comprehensively analyzes biosensing platforms originating from MDS for sensing and imaging biological analytes. We first describe a basic overview of MDS and MDS-inspired biosensing platforms (e.g., CRISPR-Cas systems, nanopore-forming proteins, and gas vesicles), followed by a critical discussion of their functions and properties. We then discuss several transduction mechanisms (optical, acoustic, magnetic, and electrical) involved in MDS-inspired biosensing. We further detail the applications of the MDS-inspired biosensors to detect a variety of analytes (nucleic acids, peptides, proteins, pathogens, cells, small molecules, and metal ions). In the end, we propose the key challenges and future perspectives in seeking new and improved MDS tools that can potentially lead to breakthrough discoveries in developing a new generation of biosensors with a combination of low cost; high sensitivity, accuracy, and precision; and fast detection. Overall, this Review gives a historical review of MDS, elucidates the principles of emulating MDS to develop biosensors, and analyzes the recent advancements, current challenges, and future trends in this field. It provides a unique critical analysis of emulating MDS to develop robust biosensors and discusses the design of such biosensors using elements found in MDS, showing that emulating MDS is a promising approach to conceptually advancing the design of biosensors.

Since the outbreak of COVID-19, the number of confirmed cases and deaths has increased globally at a dramatic speed. In view of the serious health threat to humans, this review discusses the state-of-the-art studies about fighting this disease. It summarizes the current strategies and recent advances in detecting, preventing, and treating COVID-19 and interprets the underlying mechanisms in detail. Detection of COVID-19 can be successfully achieved by multiple techniques such as polymerase chain reaction, computed tomography imaging, and nano-biosensing. Inactivated virus vaccine, nucleic acid vaccine, and different nanoparticles have been employed to effectively prevent COVID-19. A variety of agents such as antiviral agents, neutralizing antibodies, and nanotherapeutics have been developed to treat COVID-19 with exciting efficacy. Although nanobiotechnology has shown great potential in the diagnosis, prevention, and treatment of COVID-19, efforts should be made to explore new biocompatible nano-biomaterials to advance this field to clinical applications. Hence, nanobiotechnology paves a new way to detect, prevent, and treat COVID-19 effectively.

Graphene paper (GP), a macroscopic self-supporting material, has exceptional flexibility and preserves the excellent physical and chemical properties of graphene nanomaterials. But its applications in regenerative medicine remain to be further explored. Here, we biologically functionalized GP with hydroxyapatite (HA) nanorods by the use of GP-binding peptides as an affinity linker. This strategy solved two daunting challenges for regenerative medicine applications of GP: the lack of good hydrophilicity for supporting cell growth and the difficulty in forming composites by binding with nanobiomaterials. Briefly, we first screened a high-affinity GP-binding peptide (TWWNPRLVYFDY) by the phage display technique. Then we chemically conjugated the GP-binding peptide to the synthetic HA nanorods. The GP-binding peptide on the resultant HA nanorods enabled them to be bound and assembled onto the GP substrate with high affinity, forming a GP-peptide-HA composite with significantly improved hydrophilicity of GP. The composite promoted the attachment and proliferation of mesenchymal stem cells (MSCs), demonstrating its outstanding biocompatibility. Due to the unique compositions of the composite, it was also found to induce osteogenic differentiation of MSCs in vitro in the absence of other inducers in the medium, by verifying the expression of the osteogenic markers including collagen-1, bone morphogenetic proteins 2, runx-related transcription factor 2, osteocalcin, and alkaline phosphatase. Our work suggests that the GP-binding peptide can be used to link inorganic nanoparticles onto GP to facilitate the biomedical applications of GP.

Hydrogels are prevalent scaffolds for tissue regeneration because of their hierarchical architectures along with outstanding biocompatibility and unique rheological and mechanical properties. For decades, researchers have found that many materials (natural, synthetic, or hybrid) can form hydrogels using different cross-linking strategies. Traditional strategies for fabricating hydrogels include physical, chemical, and enzymatical cross-linking methods. However, due to the diverse characteristics of different tissues/organs to be regenerated, tissue-customized hydrogels need to be developed through precisely controlled processes, making the manufacture of hydrogels reliant on novel cross-linking strategies. Thus, hybrid cross-linkable materials are proposed to tackle this challenge through hybrid cross-linking strategies. Here, different cross-linkable materials and their associated cross-linking strategies are summarized. From the perspective of the major characteristics of the target tissues/organs, we critically analyze how different cross-linking strategies are tailored to fit the regeneration of such tissues and organs. To further advance this field, more appropriate cross-linkable materials and cross-linking strategies should be investigated. In addition, some innovative technologies, such as 3D bioprinting, the internet of medical things (IoMT), and artificial intelligence (AI), are also proposed to improve the development of hydrogels for more efficient tissue regeneration.

In article number 20200181, Chuanbin Mao, Mingying Yang and their co-wokers have demonstrated that nanobiotechnology holds promise for combating COVID-19. It provides nanoscale probes to detect COVID-19, nanoscale vaccines to prevent COVID-19, and nanoscale therapeutics to treat COVID-19. Because nanoparticles are comparable to the virus particles that cause COVID-19, the nanoparticles can be engineered to detect, prevent or treat COVID-19 in a more efficient manner than the other agents.

Nontoxic phage virus nanofibers are genetically engineered by Mingying Yang, Chuanbin Mao, and co-workers in article number 2001260 to first home to tumors through the blood circulation and then capture proteins that can promote blood vessel formation in the tumors. The phages are thus able to suppress tumor growth due to the inhibition of the tumor angiogenesis.