Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.

Improving salt-tolerant artificial consortium of Bacillus amyloliquefaciens for bioconverting food waste to lipopeptides.

High-salt content in food waste (FW) affects its resource utilization during biotransformation. In this study, adaptive laboratory evolution (ALE), gene editing, and artificial consortia were performed out to improve the salt-tolerance of Bacillus amyloliquefaciens for producing lipopeptide under FW and seawater. High-salt stress significantly decreased lipopeptide production in the B. amyloliquefaciens HM618 and ALE strains. The total lipopeptide production in the recombinant B. amyloliquefaciens HM-4KSMSO after overexpressing the ion transportor gene ktrA and proline transporter gene opuE and replacing the promoter of gene mrp was 1.34 times higher than that in the strain HM618 in medium containing 30 g/L NaCl. Lipopeptide production under salt-tolerant consortia containing two strains (HM-4KSMSO and Corynebacterium glutamicum) and three-strains (HM-4KSMSO, salt-tolerant C. glutamicum, and Yarrowia lipolytica) was 1.81- and 2.28-fold higher than that under pure culture in a medium containing FW or both FW and seawater, respectively. These findings provide a new strategy for using high-salt FW and seawater to produce value-added chemicals.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

An Activatable Dual Polymer Nanosystem for Photoimmunotherapy and Metabolic Modulation of Deep-Seated Tumors.

Nanomedicine in combination with immunotherapy has shown great potential in the cancer treatment, but phototherapeutic nanomaterials that specifically activate the immunopharmacological effects in deep tumors have rarely been developed due to limited laser penetration depth and tumor immune microenvironment. Herein, this work reports a newly synthesized semiconducting polymer (SP) grafted with imiquimod R837 and indoxmid encapsulated micelle (SPRIN-micelle) with strong absorption in the second near infrared window (NIR-II) that can relieve tumor immunosuppression and enhance the photothermal immunotherapy and catabolic modulation on tumors. Immune agonists (Imiquimod R837) and immunometabolic modulators (indoxmid) are covalently attached to NIR-II SP sensors via a glutathione (GSH) responsive self-immolation linker and then loaded into Pluronic F127 (F127) micelles by a temperature-sensitive critical micelle concentration (CMC)-switching method. Using this method, photothermal effect of SPRIN-micelles in deep-seated tumors can be activated, leading to effective tumor ablation and immunogenic cell death (ICD). Meanwhile, imiquimod and indoxmid are tracelessly released in response to the tumor microenvironment, resulting in dendritic cell (DC) maturation by imiquimod R837 and inhibition of both indoleamine 2,3-dioxygenase (IDO) activity and Treg cell expression by indoxmid. Ultimately, cytotoxic T-lymphocyte infiltration and tumor metastasis inhibition in deep solid tumors (9 mm) are achieved. In summary, this work demonstrates a new strategy for the combination of photothermal immunotherapy and metabolic modulation by developing a dual functional polymer system including activable SP and temperature-sensitive F127 for the treatment of deep solid tumors.

Orally-Delivered, Cytokine-Engineered Extracellular Vesicles for Targeted Treatment of Inflammatory Bowel Disease.

The use of orally-administered therapeutic proteins for treatment of inflammatory bowel disease (IBD) has been limited due to the harsh gastrointestinal environment and low bioavailability that affects delivery to diseased sites. Here, a nested delivery system, termed Gal-IL10-EVs (C/A) that protects interleukin 10 (IL-10) from degradation in the stomach and enables targeted delivery of IL-10 to inflammatory macrophages infiltrating the colonic lamina propria, is reported. Extracellular vesicles (EVs) carrying IL-10 are designed to be secreted from genetically engineered mammalian cells by a plasmid system, and EVs are subsequently modified with galactose, endowing the targeted IL-10 delivery to inflammatory macrophages. Chitosan/alginate (C/A) hydrogel coating on Gal-IL10-EVs enables protection from harsh conditions in the gastrointestinal tract and favorable delivery to the colonic lumen, where the C/A hydrogel coating is removed at the diseased sites. Gal-IL10-EVs control the production of reactive oxygen species (ROS) and inhibit the expression of proinflammatory cytokines. In a murine model of colitis, Gal-IL10-EVs (C/A) alleviate IBD symptoms including inflammatory responses and disrupt colonic barriers. Taken together, Gal-IL10-EVs (C/A) features biocompatibility, pH-responsive drug release, and macrophage-targeting as a therapeutic platform for oral delivery of bioactive proteins for treating intestinal diseases.

Anti-Tumor Immunity Induced by a Ternary Membrane System Derived From Cancer Cells, Dendritic Cells, and Bacteria.

Cancer vaccines generally are limited by insufficient tumor-specific cellular immunogenicity. Herein, a potent "ABC" ternary membrane-derived vaccine system blended from antigen-presenting mature dendritic cell membranes ("A"), bacterial E. coli cytoplasmic membranes ("B"), and cancer cell membranes ("C") is developed using a block-copolymer micelle-enabled approach. The respective ABC membrane components provide for a source of cellular immune communication/activation and enhanced accumulation in lymph nodes (A), immunological adjuvant (B), and tumor antigens (C). The introduction of dendritic cell (DC) membranes enables multiple cell-to-cell communication and powerful immune activation. ABC activates dendritic cells and promotes T-cell activation and proliferation in vitro. In vivo, ABC is 14- and 304-fold more immunogenic than binary (BC) and single (C) membrane vaccines, and immunization with ABC enhances the frequency of tumor-specific cytotoxic T lymphocytes, leading to an 80% cure rate in tumor-bearing mice. In a surgical resection and recurrence model, ABC prevents recurrence with vaccination from autologous cancer membranes, and therapeutic effects are observed in a lung metastasis model even with heterologous cancer cell membranes. ABCs formed from human cancer patient-derived tumor cells activate human monocyte-derived dendritic cells (moDC). Taken together, the ternary ABC membrane system provides the needed functional components for personalized cancer immunotherapy.

Topical Drug Delivery of Concentrated Cabazitaxel in an α-Tocopherol and DMSO Solution.

Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100 mg mL-1 . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α-tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5 µg cm-2 within 24 h), while no detectable drug permeates when CTX is dissolved in α-tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α-tocopherol, but not in pure DMSO, is reversible 8 h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75 mg mL-1 ), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50 mg mL-1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α-tocopherol solvent warrants further study as a treatment for skin malignancies.

Single and combined toxicity effects of microplastics and perfluorooctanoic acid on submerged macrophytes and biofilms.

Microplastics (MPs) and Perfluorooctanoic acid (PFOA) have contaminated nearly all types of ecosystems, including marine, terrestrial and freshwater habitats, posing a severe threat to the ecological environment. However, their combined toxicity on aquatic organisms (e.g., macrophytes) remains unknown. This study investigated single and combined toxic effects of polypropylene (PP), polyethylene (PE), polyvinylchloride (PVC), polyethylene terephthalate (PET) and PFOA on Vallisneria natans (V. natans) and associated biofilms. Results showed that MPs and PFOA significantly affected plant growth, while the magnitude of the effect was associated with concentrations of PFOA and the types of MPs, and antagonistic effects were induced at combined MPs and PFOA exposure. In addition, antioxidant responses in plants, such as promoted activities of SOD and POD, as well as increased content of GSH and MDA, were triggered effectively by exposure to MPs and PFOA alone and in combination. Ultrastructural changes revealed the stress response of leaf cells and the damage to organelles. Moreover, single and combined exposure to MPs and PFOA altered the diversity and richness of the microbial community in the leaf biofilms. These results indicated that the coexistence of MPs and PFOA can induce effective defense mechanisms of V. natans and change the associated biofilms at given concentrations in the aquatic ecosystems.

Effects of combined exposure of PVC and PFOA on the physiology and biochemistry of Microcystis aeruginosa.

Microplastics (MPs) and per- and polyfluoroalkyl substances (PFASs) have drawn significant attention as emerging threats to aquatic ecosystems. There are currently just a few investigations on the combined toxicity of PFAS and MP on freshwater microalgae. In this research, the combined toxicity of polyvinyl chloride (PVC) and perfluorooctanoic acid (PFOA) to Microcystis aeruginosa was investigated. The results indicated that the combination of these pollutants inhibited the growth of M. aeruginosa and promoted the synthesis and release of Microcystin-LR (MC-LR). Individual and combined exposure caused different responses to cellular oxidative stress. Under the Individual exposure of PFOA, when the concentration was greater than 20.0 mg/L, the catalase (CAT) activity increased significantly, and when it was greater than 100.0 mg/L, the malondialdehyde (MDA) content increased significantly, but there is no significant change under combined exposure. PVC and PFOA exposure also caused physical damage to the algal cells and reduced the content of extracellular polymer substances (EPS) based on analysis of cell morphology. Metabolic analysis revealed that carbohydrate metabolism and amino acid metabolism of the algae were affected. The current study offers a fresh theoretical framework for MPs and PFASs environmental risk evaluations.

Imaging of Gastrointestinal Tract Ailments.

Gastrointestinal (GI) disorders comprise a diverse range of conditions that can significantly reduce the quality of life and can even be life-threatening in serious cases. The development of accurate and rapid detection approaches is of essential importance for early diagnosis and timely management of GI diseases. This review mainly focuses on the imaging of several representative gastrointestinal ailments, such as inflammatory bowel disease, tumors, appendicitis, Meckel's diverticulum, and others. Various imaging modalities commonly used for the gastrointestinal tract, including magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT), and photoacoustic tomography (PAT) and multimodal imaging with mode overlap are summarized. These achievements in single and multimodal imaging provide useful guidance for improved diagnosis, staging, and treatment of the corresponding gastrointestinal diseases. The review evaluates the strengths and weaknesses of different imaging techniques and summarizes the development of imaging techniques used for diagnosing gastrointestinal ailments.

Metal coordination micelles for anti-cancer treatment by gene-editing and phototherapy.

CRISPR-Cas9 is a central focus of the emerging field of gene editing and photodynamic therapy (PDT) is a clinical-stage ablation modality combining photosensitizers with light irradiation. But metal coordination biomaterials for the applications of both have rarely been investigated. Herein, Chlorin-e6 (Ce6) Manganese (Mn) coordination micelles loaded with Cas9, termed Ce6-Mn-Cas9, were developed for augmented combination anti-cancer treatment. Manganese played multiple roles to facilitate Cas9 and single guide RNA (sgRNA) ribonucleoprotein (RNP) delivery, Fenton-like effect, and enhanced endonuclease activity of RNP. Histidine (His)-tagged RNP could be coordinated to Ce6 encapsulated in Pluronic F127 (F127) micelles by simple admixture. Triggered by ATP and endolysosomal acidic pH, Ce6-Mn-Cas9 released Cas9 without altering protein structure or function. Dual guide RNAs were designed to target the antioxidant regulator MTH1 and the DNA repair protein APE1, resulting in increased oxygen and enhanced PDT effect. In a murine tumor model, Ce6-Mn-Cas9 inhibited tumor growth with the combination therapy of PDT and gene editing. Taken together, Ce6-Mn-Cas9 represents a new biomaterial with a high degree of versatility to enable photo- and gene-therapy approaches.

Circ_0027470 promotes cadmium exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and stimulating SHH signaling pathway.

Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.

CRISPR/Cas9 and Chlorophyll Coordination Micelles for Cancer Treatment by Genome Editing and Photodynamic Therapy.

CRISPR/Cas9-based gene therapy and photodynamic therapy both show promise for cancer treatment but still have their drawbacks limited by tumor microenvironment and long treatment duration. Herein, CRISPR/Cas9 genome editing and photodynamic strategy for a synergistic anti-tumor therapeutic modality is merged. Chlorophyll (Chl) extracted from natural green vegetables is encapsulated in Pluronic F127 (F127) micelles and Histidine-tagged Cas9 can be effectively chelated onto micelles via metal coordination by simple incubation, affording Cas9-Chl@F127 micelles. Mg2+ acts as an enzyme cofactor to correlatively enhance Cas9 gene-editing activity. Upon laser irradiation, Chl as an effective photosensitizer generates reactive oxygen species (ROS) to kill tumor cells. Meanwhile, CRISPR/Cas9, mediated by dual deliberately designed gRNAs of APE1 and NRF2, can reprogram the tumor microenvironment by increasing the intracellular oxygen accumulation and impairing the oxidative defense system of tumor cells. Cas9-Chl@F127 micelles can responsively release Cas9 in the presence of abundant ATP or low pH in tumor cells. In a murine tumor model, Cas9-Chl@F127 complexed with dual gRNAs including APE1 and NRF2 significantly inhibits the tumor growth. Taken together, Cas9-Chl@F127 micelles, representing the first Chl-based green biomaterial for the delivery of Cas9, show great promise for the synergistic anti-tumor treatment by PDT and gene editing.

Current development of cabazitaxel drug delivery systems.

The second-generation taxane cabazitaxel has been clinically approved for the treatment of metastatic castration-resistant prostate cancer after docetaxel failure. Compared with the first-generation taxanes paclitaxel and docetaxel, cabazitaxel has potent anticancer activity and is less prone to drug resistance due to its lower affinity for the P-gp efflux pump. The relatively high hydrophobicity of cabazitaxel and the poor aqueous colloidal stability of the commercial formulation, following its preparation for injection, presents opportunities for new cabazitaxel formulations with improved features. This review provides an overview of cabazitaxel drug formulations and hydrophobic taxane drug delivery systems in general, and particularly focuses on emerging cabazitaxel delivery systems discovered in the past 5 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Impacts of pollution heterogeneity on population exposure in dense urban areas using ultra-fine resolution air quality data.

Traditional air quality data have a spatial resolution of 1 km or above, making it challenging to resolve detailed air pollution exposure in complex urban areas. Combining urban morphology, dynamic traffic emission, regional and local meteorology, physicochemical transformations in air quality models using big data fusion technology, an ultra-fine resolution modeling system was developed to provide air quality data down to street level. Based on one-year ultra-fine resolution data, this study investigated the effects of pollution heterogeneity on the individual and population exposure to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and ozone (O3) in Hong Kong, one of the most densely populated and urbanized cities. Sharp fine-scale variabilities in air pollution were revealed within individual city blocks. Using traditional 1 km average to represent individual exposure resulted in a positively skewed deviation of up to 200% for high-end exposure individuals. Citizens were disproportionally affected by air pollution, with annual pollutant concentrations varied by factors of 2 to 5 among 452 District Council Constituency Areas (DCCAs) in Hong Kong, indicating great environmental inequities among the population. Unfavorable city planning resulted in a positive spatial coincidence between pollution and population, which increased public exposure to air pollutants by as large as 46% among districts in Hong Kong. Our results highlight the importance of ultra-fine pollutant data in quantifying the heterogeneity in pollution exposure in the dense urban area and the critical role of smart urban planning in reducing exposure inequities.

Design and application of organic contrast agents for molecular imaging in the second near infrared (NIR-II) window.

Optical imaging in the second near-infrared (NIR-II) window has attracted interest in recent years because of the merits of reduced light scattering, minimal autofluorescence from biological tissues and deeper penetration depth in this wavelength range. In this review, we summarize NIR-II organic contrast agents reported in the past decade for photoacoustic and fluorescence imaging including members of the cyanine family, D-A-D structure dyes, phthalocyanines and semiconducting polymers. Improved imaging contrast and higher resolution could be favorably achieved by rational design of NIR-II fluorophores by tuning their properties including molar extinction coefficient, fluorescence quantum yield, emission wavelength and others. A wide variety of applications using NIR-II dyes has been realized including imaging of tumors, lymphatics, brains, intestines and others. Emerging applications such as targeted imaging and activable imaging with improved resolution and sensitivity have been demonstrated by innovative chemical modification of NIR-II dyes. Looking forward, rational design of improved NIR-II dyes for advanced bioimaging is likely to remain an area of interest for next-generation potential approaches to disease diagnosis.

Manganese Coordination Micelles That Activate Stimulator of Interferon Genes and Capture In Situ Tumor Antigens for Cancer Metalloimmunotherapy.

Cancer immunotherapy holds great promise but is generally limited by insufficient induction of anticancer immune responses. Here, a metal micellar nanovaccine is developed by the self-assembly of manganese (Mn), a stimulator of interferon genes (STING) agonist (ABZI) and naphthalocyanine (ONc) coordinated nanoparticles (ONc-Mn-A) in maleimide-modified Pluronic F127 (malF127) micelles. Owing to synergy between Mn and ABZI, the nanovaccine, termed ONc-Mn-A-malF127, elevates levels of interferon-ß (IFNß) by 324- and 8-fold in vivo, compared to use of Mn or ABZI alone. As such, the activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING pathway induces sufficient dendritic cell (DC) maturation, eventually resulting in the death of CD8+ T cell-sensitive tumors and CD8+ T cell-resistant tumors by simultaneously promoting cytotoxic CD8+ T cells and NK cells, respectively. Furthermore, with ONc used as a Mn chelator and an efficient photosensitizer, photoinduced immunogenic cell death (ICD) of tumor cells releases damage-associated molecular patterns (DAMPs) and neoantigens from dying primary tumor cells upon laser irradiation, which are captured in situ by malF127 in tumor cells and then transported to DCs. After laser treatment, in addition to the photothermal therapy, immune responses characterized by the level of IFNß are further elevated by another 4-fold. In murine cancer models, ICD-based metalloimmunotherapy using the ONc-Mn-A-malF127 nanovaccine in a single dose by intravenous injection achieved eradication of primary and distant tumors. Taken together, ONc-Mn-A-malF127 offers a nanoplatform to enhance anticancer efficacy by metalloimmunotherapy and photoinduced ICD based immunotherapy with strong abscopal effect.

Colistin Crosslinked Gemcitabine Micelles to Eliminate Tumor Drug Resistance Caused by Intratumoral Microorganisms.

In the tumor microenvironment, there exist microorganisms that metabolize anticancer drugs, leading to chemotherapy failure. To solve this problem, herein, we develop antibiotic and anticancer drug co-delivery micelles, termed colistin crosslinked gemcitabine micelle (CCGM). A self-immolative linker enables colistin and gemcitabine to be released on demand without affecting their antibacterial and anticancer effects. Once CCGM is delivered to the tumor microenvironment, intracellular glutathione triggers the release of colistin and gemcitabine, inhibiting the growth of microbes in the tumor, thus eliminating the microbe-induced drug resistance of tumor.

The Impact of Cyanobacteria Blooms on the Aquatic Environment and Human Health.

Cyanobacteria blooms are a global aquatic environment problem. In recent years, due to global warming and water eutrophication, the surface cyanobacteria accumulate in a certain area to form cyanobacteria blooms driven by wind. Cyanobacteria blooms change the physical and chemical properties of water and cause pollution. Moreover, cyanobacteria release organic matter, N (nitrogen) and P (phosphorus) into the water during their apoptosis, accelerating the eutrophication of the water, threatening aquatic flora and fauna, and affecting the community structure and abundance of microorganisms in the water. Simultaneously, toxins and carcinogens released from cyanobacteria can be enriched through the food chain/web, endangering human health. This study summarized and analyzed the research of the influence of cyanobacteria blooms on the aquatic environment and human health, which is helpful to understand further the harm of cyanobacteria blooms and provide some reference for a related research of cyanobacteria blooms.

Rapid Detection of Aspergillus flavus and Quantitative Determination of Aflatoxin B1 in Grain Crops Using a Portable Raman Spectrometer Combined with Colloidal Au Nanoparticles.

Aspergillus flavus and Aflatoxins in grain crops give rise to a serious threat to food security and cause huge economic losses. In particular, aflatoxin B1 has been identified as a Class I carcinogen to humans by the International Agency for Research on Cancer (IARC). Compared with conventional methods, Surface-Enhanced Raman Scattering (SERS) has paved the way for the detection of Aspergillus flavus and Aflatoxins in grain crops as it is a rapid, nondestructive, and sensitive analytical method. In this work, the rapid detection of Aspergillus flavus and quantification of Aflatoxin B1 in grain crops were performed by using a portable Raman spectrometer combined with colloidal Au nanoparticles (AuNPs). With the increase of the concentration of Aspergillus flavus spore suspension in the range of 102-108 CFU/mL, the better the combination of Aspergillus flavus spores and AuNPs, the better the enhancement effect of AuNPs solution on the Aspergillus flavus. A series of different concentrations of aflatoxin B1 methanol solution combined with AuNPs were determined based on SERS and their spectra were similar to that of solid powder. Moreover, the characteristic peak increased gradually with the increase of concentration in the range of 0.0005-0.01 mg/L and the determination limit was 0.0005 mg/L, which was verified by HPLC in ppM concentration. This rapid detection method can greatly shorten the detection time from several hours or even tens of hours to a few minutes, which can help to take effective measures to avoid causing large economic losses.