Glioblastoma (GBM) treatment faces a significant challenge due to the blood-brain barrier (BBB) restricting therapeutic delivery. In this study, we found that inactivated and attenuated meningitis bacteria (e.g., Escherichia coli K1) intracellularly loaded with nanoagents could safely and effectively bypass the BBB even when injected intravenously into mice at a dose of ~10⁷ CFU since the vehicles preserved the bacteria’s structure and chemotaxis while removing their pathogenicity. We demonstrated bacteria could internalize glucose polymer, indocyanine green and stimulator of interferon genes (STING) agonists (e.g., SR717)-modified silica nanoparticles through the bacteria-specific ATP-binding cassette sugar transporter pathway. As a result, the developed system could deliver approximately five times more nanoagents to the brain than free nanoagents. Upon 808-nm irradiation, the indocyanine green induced photothermal effects that destroyed the bacteria, releasing the SR717, which triggered adaptive antitumor immunity, and the bacterial remnants further induced innate antitumor immunity. Our findings demonstrate that this inactivated nanobacteria system effectively treats GBM in mice, suggesting potential for broader applications in central nervous system disorders.

Silicon-based nanomaterials, known for their unique properties and favorable biocompatibility, significantly impact sectors like energy, electronics, and biomedicine. Recently, metal-organic frameworks (MOFs) have emerged as promising candidates for biomedicine, characterized by adjustable chemical composition, high porosity, and biodegradability. However, the combination of silicon with MOFs to create silicon-based MOF nanostructures (SiMOFs) remains underexplored. Herein, we establish a diverse library of SiMOFs with various nanostructures, including flower-like, capsule-like, hexagonal snowflake-like, and necklace-like morphologies via microwave-assisted synthesis. These SiMOFs, with their spacious interiors, are ideal for drug delivery. They are used to load drugs and create drug-loaded SiMOFs (e.g., SiFeO). SiFeO exhibits excellent photothermal effects and high ROS generation capacity, enabling synergistic treatments involving chemo-chemodynamic-photothermal therapy. This approach efficiently triggers immunogenic cell death (ICD) and demonstrates excellent antitumor efficacy in vivo. Immunofluorescence staining reveals that the synergistic therapy can modulate the tumor microenvironment (TME) by reducing M2-phenotype macrophages, increasing the activation of antigen-presenting cells (APCs), enhancing the infiltration of CD4⁺ and CD8⁺ T cells, elevating Granzyme B production, and decreasing the presence of immunosuppressive regulatory T cells (Tregs). Consequently, drug-loaded SiMOFs-mediated combination therapy effectively reverses the immunosuppressive TME and activates robust antitumor immune responses by inducing ICD in tumor cells, ultimately achieving superior anticancer efficacy.

Despite sufficient studies performed in non-primate animal models, there exists scanty information obtained from pilot trials in non-human primate animal models, severely hindering nanomaterials moving from basic research into clinical practice. We herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal models. Typically, taking advantages of strong and stable fluorescence of the small-sized (diameter: ~ 5 nm) silicon-based nanoparticles (SiNPs), lymphatic drainage patterns can be vividly visualized in a real-time manner, and lymph nodes (LN) are able to be sensitively detected and precisely excised from small animal models (e.g., rats and rabbits) to non-human primate animal models (e.g., cynomolgus macaque (Macaca fascicularis) and rhesus macaque (Macaca mulatta)). Compared to clinically used invisible near-infrared (NIR) lymphatic tracers (i.e., indocyanine green (ICG); etc.), we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term manners. Thorough toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs probes. We expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic, especially in the field of cancer treatment.

Artificial optical microfingerprints, known as physically unclonable functions (PUFs) offer a groundbreaking approach for anti-counterfeiting. However, these PUFs artificial optical microfingerprints suffer from a limited number of challenge-response pairs, making them vulnerable to machine learning (ML) attacks when additional error-correcting units are introduced. This study presents a pioneering demonstration of artificial optical microfingerprints that combine the advantages of PUFs, a large encoding capacity algorithm, and reliable deep learning authentication against ML attacks. Our approach utilizes the triple-mode PUFs, incorporating bright-field, multicolor fluorescence wrinkles, and the topography of surface enhanced Raman scattering in the mechanical and optical layers. Notably, the quaternary encoding of these PUFs artificial microfingerprints allows for an encoding capacity of 6.43 × 10²⁴⁰⁸² and achieves 100% deep learning recognition accuracy. Furthermore, the PUFs artificial optical microfingerprints exhibit high resilience against ML attacks, facilitated by generative adversarial networks (GAN) (with mean prediction accuracy of ~ 85.0%). The results of this study highlight the potential of utilizing up to three PUFs in conjunction with a GAN training system, paving the way for achieving encoded information that remains resilient to ML attacks.

Traditional photothermal agents of indocyanine green (ICG) have poor stability, short circulation time, and poor brain permeability due to the blood–brain barrier (BBB), greatly impairing their therapeutic efficacy in glioblastoma (GBM). Herein, we develop a novel kind of SiNPs-based nanoprobes to bypass the BBB for photothermal therapy of GBM. Typically, the SiNPs-based nanoprobes are composed of the particle itself, the BBB-targeting ligand of glucosamine (G), and the therapeutic agent of ICG. We demonstrate that the as-synthesized nanoprobes could cross the BBB through glucose transporter-1 (GLUT1)-mediated transcytosis, followed by accumulation at GBM tissues in mice. Compared with free ICG, G-ICG-SiNPs show stronger stability (for example, the fluorescence intensity of G-ICG-SiNPs loaded with the same dose of ICG decays by 34.6% after 25 days of storage, while the fluorescence intensity of ICG decays by 99.5% under the same conditions). Furthermore, the blood circulation time of G-ICG-SiNPs increases by about 17.3-fold compared with their ICG counterparts. After injection of the therapeutic agents into the GBM-bearing mice, GBM-surface temperature rises to 45.3 °C in G-ICG-SiNPs group after 5-min 808 nm irradiation but climbs only to 36.1 °C in equivalent ICG group under the identical conditions, indicating the superior photothermal effects of G-ICG-SiNPsin vivo.

The production of bimetallic nanoparticles with ultrasmall sizes is the constant pursuit in chemistry and materials science because of their promising applications in catalysis, electronics and sensing. Here we report ambient-temperature preparation of bimetallic NPs with tunable size and composition using microfluidic-controlled co-reduction of two metal precursors on silicon surface. Instead of free diffusion of metal ions in bulk system, microfluidic flow could well control the local ions concentration, thus leading to homogenous and controllable reduction rate among different nucleation sites. By controlling precursor concentration, flow rate and reaction time, we rationally design a series of bimetallic NPs including Ag-Cu, Ag-Pd, Cu-Pt, Cu-Pd and Pt-Pd NPs with ultrasmall sizes (~ 3.0 nm), tight size distributions (relative standard deviation (RSD) < 21%), clean surface, and homogenous elemental compositions among particles (standard deviation (SD) of weight ratios < 3.5%). This approach provides a facile, green and scalable method toward the synthesis of diverse bimetallic NPs with excellent activity.

Fluorescein angiography (FA) is a standard imaging modality for evaluating vascular abnormalities in retina-related diseases, which is recognized as the major cause of vision loss. Long-term and real-time fundus angiography is of great importance in preclinical research, nevertheless remaining big challenges up to present. In this study, we demonstrate that long-term fluorescence imaging of retinal vessels is enabled through a kind of fluorescent nanoagents, which is made of small-sized (hydrodynamic diameter: ~ 3 nm) silicon nanoparticles (SiNPs) featuring strong fluorescence, robust photostability, lengthened blood residency and negligible toxicity. In particular, the presented SiNPs-based nanoagents are capable of imaging retinal capillaries in ~ 10 min, which is around 10-fold longer than that (~ 1 min) of fluorescein sodium (FS, known as the most widely used contrast agents for FA in clinic). Taking cynomolgus macaques as non-human primate-animal model, we further demonstrate the feasibility of real-time diagnosis of retinal diseases (e.g., age-related macular degeneration (AMD)) through dynamic monitoring of vascular dysfunction.

Recommended as a medical emergency, infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness. Herein, we present a kind of theranostic agents, which are made of vancomycin (Van)-modified fluorescent silicon nanoparticles (SiNPs-Van), enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner. Typically, the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro (5 min) and in vivo (10 min), making them an efficacious diagnostic agent for the detection of bacterial keratitis. In addition, the SiNPs-Van feature distinct antimicrobial activity, with superior activity of 92.5% at a concentration of 0.5 μg/mL against Staphylococcus aureus (S. aureus); comparatively, the antimicrobial rate of free vancomycin is 23.3% at the same concentration. We further explore the SiNPs-Van agents as eye drops for therapy of S. aureus-induced bacterial keratitis on rat model. Represented by slit-lamp scores, the keratitis severity of SiNPs-Van-treated corneas is 3.4, which is 59.6% and 77.3% slighter than vancomycin-(8.2 score) and PBS-treated corneas (15.0 score), respectively. The infected corneas recover to normal (1 score) after 7-d of SiNPs-Van treatment. Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents, especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.

Optical silicon (Si)-based materials are highly attractive due to their widespread applications ranging from electronics to biomedicine. It is worth noting that while extensive efforts have been devoted to developing fluorescent Si-based structures, there currently exist no examples of Si-based materials featuring phosphorescence emission, severely limiting Si-based wide-ranging optical applications. To address this critical issue, we herein introduce a kind of Si-based material, in which metal-organic frameworks (MOFs) are in-situ growing on the surface of Si nanoparticles (SiNPs) assisted by microwave irradiation. Of particular significance, the resultant materials, i.e., MOFs-encapsulated SiNPs (MOFs@SiNPs) could exhibit pH-responsive fluorescence, whose maximum emission wavelength is red-shifted from 442 to 592 nm when the pH increases from 2 to 13. More importantly, distinct room-temperature phosphorescence (maximum emission wavelength: 505 nm) could be observed in this system, with long lifetime of 215 ms. Taking advantages of above-mentioned unique optical properties, the MOFs@SiNPs are further employed as high-quality anti-counterfeiting inks for advanced encryption. In comparison to conventional fluorescence anti-counterfeiting techniques (static fluorescence outputs are generally used, thus being easily duplicated and leading to counterfeiting risk), pH-responsive fluorescence and room-temperature phosphorescence of the resultant MOFs@SiNPs-based ink could offer advanced multi-modal security, which is therefore capable of realizing higher-level information security against counterfeiting.

Fluorescent silicon nanoparticles (SiNPs) bring exciting opportunities for long-awaited silicon-based optical application, while intrinsic indirect band gap of silicon severely limits photoluminescent quantum yield (PLQY) of SiNPs. To address this critical issue, we herein demonstrate a facile and general method, i.e., solvent polarity-induced photoluminescence enhancement (SPIPE), yielding several-fold increase in quantum yield (QY) of SiNPs. Typically, different kinds of 4-substituented-1,8-naphthalic anhydride molecules, i.e., 4-Br-1,8-naphthalic anhydride (BNA), 4-triphenylamino-1,8-naphthalic anhydride (TPNA), and 4-dimethylamino-1,8-naphthalic anhydride (DMNA), are rationally designed and synthesized, which serve as surface ligands for the production of BNA-, TPNA-, and DMNA-capped small-sized (diameter: ~ 3.8–5.8 nm) SiNPs with QY of ~ 8%, ~ 15%, ~ 16%, respectively. Of particular significance, QY of the resultant SiNPs could be greatly enhanced from ~ 10% to ~ 50% through the SPIPE strategy. Taken together with the theoretical calculation and the results of time-correlated single photon counting, we reveal that actived excited-state charge transfer interactions between surface-covered ligand and silicon oxide coating would be responsible for the observed QY enhancement. Moreover, other five kinds of solvents (i.e., methanol, isopropanol, dimethyl sulfoxide, N, N-dimethylformamide, and acetonitrile) are further employed for the SiNPs treatment, and similar improvement of QY values are observed, convincingly demonstrating the universal evidence of SPIPE of the SiNPs.