Journal of Nanobiotechnology最新文献

The liver, functioning as an endocrine organ, secretes a variety of substances that influence the activities of other body organs. Conversely, molecules generated by organs such as bone, the gut, and adipose tissue can also impact liver function. Accumulating evidence suggests bidirectional communication between the liver and other organs. However, research on how extracellular vesicles (EVs), which transport active molecular mediators, contribute to this interorgan communication is still in its nascent stages. EVs are capable of transporting functional molecules, including lipids, nucleic acids, and proteins, thereby affecting recipient cells across different organs at the biological level. This review examines the role of EVs in facilitating bidirectional communication between the liver and other organs such as bone, the cardiovascular system, the gut, the pancreas, the brain, the lungs, the kidneys, and adipose tissue. It explores their potential in disease treatment and highlights the challenges in understanding EV-mediated interorgan interactions. The contribution of mediator-carrying EVs to two-way communication between the liver and other organs remains an area of ongoing investigation. Future research will provide a more comprehensive theoretical foundation to clarify the precise mechanisms governing communication between the liver and other organs, pinpoint medical targets, and expand the application of EVs within the realm of precision medicine.

Periodontitis is a chronic inflammatory disease caused by plaque. In order to remove pathogens and promote tissue repair, the following steps need to be taken simultaneously: localizing the diseased area, improving the anaerobic microenvironment, as well as addressing the anti-inflammatory and osteogenic needs. This study aims to address these issues by developing a responsive near-infrared-IIb nanozyme system (DMUP), assembled from lanthanide-doped down-converted nanoparticles and multi-enzymatically active nanozyme. DMUP binds to bacterial membranes via the bacterial targeting peptide ubiquicidin_29-41 (UBI_29-41). Upon responding to the inflammatory microenvironment, it releases manganese (Mn) nanozyme and paeonol (Pae), and localized infected areas by fluorescent bacterial imaging in the near-infrared IIb (NIR-IIb) region. In particular, the released Mn nanozyme reacts with hydrogen peroxide in the inflammatory microenvironment to generate oxygen (O₂) in situ, thereby improving the anoxic environment to inhibit anaerobic bacteria. On the other hand, as a metal oxide nanozyme, Mn nanozyme scavenges reactive oxygen species (ROS) by mimicking the cascade process of superoxide dismutase and catalase. The phenolic antioxidant Pae shifts macrophages from pro-inflammatory (M1-type) to anti-inflammatory (M2-type) through the Akt/mTOR pathway. It can synergize with Mn nanozyme to regulate the inflammatory microenvironment, thereby reducing inflammation, promoting osteogenic genes expression, and accelerating periodontal tissues regeneration.

Background: Environmentally responsive nanoscale biocide delivery system enhances smart, regulated, and synergistic biocide application with precise biocide release. In this study, pectin-modified dendritic mesoporous silica nanoparticles (DMSNs) was used as a carrier to successfully construct a microenvironment-responsive (pH, temperature and enzyme) eugenol nano-biocide delivery system for the control of Ralstonia solanacearum infection.

Results: The results showed that the specific surface area, pore size and surface activity of DMSNs significantly influence the biocide loading of eugenol, and the biocide loading capability was up to 72.50%. Eu@DMSNs/Pec had significant pH and pectinase stimulating effects, with varying release amounts under different temperature conditions. Compared with eugenol alone, Eu@DMSNs/Pec significantly enhanced the efficacy of eugenol. DMSNs assisted eugenol to induce peroxidation damage, produce ROS (•O₂^-, •OH and ¹O₂), achieve synergistic antibacterial effects, and had better rain erosion resistance and foliar retention rate based on pectin wettability and adhesion. Eu@DMSNs/Pec-FITC showed demonstrated efficient transport characteristics in tomato roots, stems and leaves, which enhanced the control effect on tomato bacterial wilt. In addition, Eu@DMSNs/Pec exert minimal influence on tomato seed germination and root growth, and have low toxicity to non-target organisms such as earthworms. Therefore, Eu@DMSNs/Pec environment-responsive nano-controlled release nanocarrier can effectively achieve accurate biocide release and reduce biocide dosage.

Conclusion: This work not only provides a pectin-modified DMSNs-based eugenol nanoscale biocide delivery system in response to specific environmental conditions of R. solanacearum infection but also elucidates the eugenol biocide loading, selective release ability and antibacterial mechanism of the system.

Background: Aberrant proliferation and inflammation of fibroblast-like synoviocytes (FLSs) significantly contribute to the pathogenesis of rheumatoid arthritis (RA). Deficiency of hydrogen sulfide (H₂S) is a driving force for the development of RA, and the short half-life of the H₂S-releasing donor sodium hydrosulfide (NaHS) limits its clinical application in RA therapy. Designing a targeted delivery system with slow-release properties for FLSs could offer novel strategies for treating RA.

Methods: Herein, we designed a strategy to achieve slow release of H₂S targeted to the synovium, which was accomplished by synthesizing NaHS-CY5@mesoporous silic@LNP targeted peptide Dil (NaHS@Cy5@MS@SP) nanoparticles.

Results: Our results demonstrated that NaHS@Cy5@MS@SP effectively targets FLSs, upregulates H₂S and its-producing enzyme cystathionine-γ-lyase (CSE) in the joints of arthritic mice. Overexpression of CSE inhibited the proliferation, migration, and inflammation of FLSs upon lipopolysaccharide (LPS) exposure, effects that were mimicked by NaHS@Cy5@MS@SP. In vivo studies showed that NaHS@Cy5@MS@SP achieved a threefold higher AUC_inf than that of free NaHS, significantly improving the bioavailability of NaHS. Further, NaHS@Cy5@MS@SP inhibited synovial hyperplasia and reduced bone and cartilage erosion in the DBA/1J mouse model of collagen-induced arthritis (CIA), which was superior to NaHS. RNA sequencing and molecular studies validated that NaHS@Cy5@MS@SP inactivated the Hedgehog signaling pathway in FLSs, as evidenced by reductions in the protein expression of SHH, SMO, GLI1 and phosphorylated p38/MAPK.

Conclusion: This study highlights NaHS@Cy5@MS@SP as a promising strategy for the controlled and targeted delivery of H₂S to synoviocytes, offering potential for RA management.

Radiotherapy is a leading method for cancer treatment, effectively eliminating cancer cells but often causing collateral damage to surrounding healthy tissue. Radiosensitizers aim to enhance the therapeutic effects of radiotherapy while minimizing harm to normal cells. We recently reported atomically-precise gold nanoclusters, Au₂₂(Lys-Cys-Lys)₁₆, synthesized via a photochemical method coupled with a novel accelerated size-focusing procedure. These nanoclusters exhibit a distinct luminescence emission profile, reflecting exceptional optical purity and the absence of contamination from other nanocluster species. They demonstrate efficient oxygen radicals generation under light irradiation. In this study, we comprehensively evaluated the radiosensitization potential of Au₂₂(Lys-Cys-Lys)₁₆ nanoclusters in vitro and in vivo, alongside their pharmacokinetics, biodistribution and toxicity. The nanoclusters demonstrated high stability under physiological conditions and efficient internalization in tumor cells, achieving dose enhancement factors of 2.0 and 1.6 in KB and 4T1 tumor cells, respectively, under 225 kVp X-ray irradiation. Mechanistic investigations revealed enhanced radiation-induced DNA damage and disruption of DNA repair pathways. The radiosensitizing effects were further validated in radioresistant pancreatic ductal adenocarcinoma cells using the clonogenic assay and γH2AX analysis of double-strand breaks, as well as in a duck chorioallantoic membrane model. With ultra small size (~ 1.7 nm) and favorable surface framework, the nanoclusters exhibited relevant pharmacokinetics (circulation half-life, t₁_/₂ = 10.4 h) and renal clearance. In a KB tumor-bearing mouse model, Au₂₂(Lys-Cys-Lys)₁₆ significantly delayed tumor progression and prolonged survival under 8 Gy irradiation without observed side-effects. These findings establish Au₂₂(Lys-Cys-Lys)₁₆ nanoclusters as a potentially translatable radiosensitizer, advancing cancer radiotherapy strategies.

Cryopreservation techniques have been widely used, especially in biomedical applications and preservation of germplasm resources. Ideally, biological materials would maintain functional integrity as well as a normal structure and can be recovered when needed. However, this tool does not work all the time. Ice formation and growth are the key challenges. The other major reason is that the cryoprotective agents (CPAs) currently used do not meet these needs and are always accompanied by their cytotoxicity. A comprehensive and synergistic approach that focuses on the overall frozen biological system is crucial for the evolution of cryopreservation methods. In this review, we first summarize the fundamental damage mechanisms during cryopreservation, as well as common cryoprotectants and their limitations. Next, we discuss materials that interact with ice to improve cryopreservation outcomes. We evaluated natural and synthetic materials, including sugars and polymers, AFPs and mimics, ice nucleators, and hydrogels. In addition, biochemical regulation, which enhances the tolerance of biosamples to cryopreservation-induced stresses, was also mentioned. Nanotechnology, cell encapsulation, cryomesh, and isochoric freezing, such scalable approaches, are further discussed for cryopreservation. Finally, future research directions in this field for efficient cryopreservation are proposed. We emphasized the need for multidisciplinary progress to address these challenges. The combination of cryobiology mechanisms with technologies, such as synthetic biology, nanotechnology, microfluidics, and 3D bioprinting, is highlighted.

Limited treatment response and inadequate monitoring methods stand firmly before successful immunotherapy. Recruiting and activating immune cells in the hypoxic tumor microenvironment is the key to reversing immune suppression and improving immunotherapy efficacy. In this study, biomimetic oxygen-delivering nanoparticles (CmPF) are engineered for homologous targeting and hypoxia alleviation within the tumor environment. CmPF targets the tumor microenvironment and delivers oxygen to reduce hypoxia, thereby promoting immune cell activity at the tumor site. In addition, granzyme B-targeted positron emission tomography (PET) imaging is employed to monitor immune cell activity changes in response to immunotherapy efficacy in vivo. The combination of CmPF with carboplatin and PD-1 inhibitors significantly suppresses tumor growth by 2.4-fold, exhibiting the potential of CmPF to enhance the efficacy of immunotherapy. Immunohistochemistry further confirms increased expression of key immune markers, highlighting the reprogramming of the tumor microenvironment. This study demonstrates that hypoxia alleviation enhances tumor immunotherapy efficacy and introduces a non-invasive PET imaging method for dynamic, real-time assessment of therapeutic response.

¹³¹I therapy is clinically unfeasible for anaplastic thyroid carcinoma (ATC), due to lack of active targets and ATC's resistance to radiation. Novel radionuclide-labeled targeted nano-drug delivery systems have exhibited the potential of prominent tumor imaging and remedy. Capitalizing on recent research achievements in nanotechnology and nuclear medicine, we sought to develop a radiolabeled nano-drug, which could specifically accumulate in ATCs via tumor-selective targeted delivery system and which could treat the tumors with both targeted and radionuclide therapeutics. Epidermal growth factor receptor (EGFR) and mutant P53 expressions were positive in 80% and 60% of patients with ATC, respectively. Herein, core-shell nanoparticles-based poly (ethyleneglycol)-crosslinker (PEG-CL) was fabricated, by encapsulating bovine serum albumin (BSA) inside the core and an enzyme with various tyrosine residues for ¹³¹I radiolabeling, and by loading anlotinib, a multi-kinase inhibitor which can site-selectively target overexpressed EGFR in ATC cells and which also suppresses angiogenesis, onto the PEG-CL shell surface. The Anlotinib-BSA nano-capsule (nBSA) showed a mostly uniform size distribution centering at 21-23 nm, and the nano-drug had a characteristic absorption peak at the wavelength of 325 nm. The Anlotinib-nBSA had a high labeling efficiency with the radiochemical purity being approximately 100%. The cellular uptake efficiency of Anlotinib-nBSA-¹³¹I was much higher than that of free ¹³¹I in both 8305C (3.6% vs 0.0%) and C643 (7.0% vs 0.1%; with a higher EGFR expression level) ATC cell lines. Anlotinib-nBSA-¹³¹I showed the strongest cytotoxicity against ATC cells with different concentrations of anlotinib, and induced the highest rate of apoptosis (C643 cells, 81.7%). The nanoparticles could actively target tumor surface with anlotinib exhibiting enhanced radio-sensitization effects by functionally upregulating P53 and Bax. In vivo SPECT/CT imaging showed that the concentration of Anlotinib-nBSA-¹²⁵I in tumors peaked at 24 h, and the intense signal persisted for at least one week. Anlotinib-nBSA-¹³¹I showed the strongest tumor inhibition effects in tumor-bearing mice, with no evident pathological changes observed. Together, the optimal nanoparticles co-loading anlotinib and ¹³¹I satisfactorily demonstrated efficient drug delivery and prominent antitumor effects both in vitro and in vivo, without obvious in vivo bio-toxicity. Our innovation could offer novel effective strategies for targeted management of ATC, a highly-aggressive disease with dismal prognosis.

Diabetic wound healing remains a significant clinical challenge because of hyperglycaemia-induced cellular senescence, impaired angiogenesis, and chronic inflammation. To address these issues, we developed a multifunctional hydrogel (GelMA/PNS/Alg@IGF-1) that integrates gelatine methacryloyl (GelMA), Panax notoginseng saponins (PNS), and sodium alginate microspheres encapsulating insulin-like growth factor-1 (IGF-1). This hydrogel was engineered to achieve gradient and sustained release of bioactive agents to target senescence and promote vascular repair. In vitro studies demonstrated that the hydrogel significantly reduced oxidative stress, suppressed senescence markers and senescence-associated secretory phenotypes, and restored endothelial cell function under high-glucose conditions by inhibiting NF-κB pathway activation. Transcriptomic analysis revealed the modulation of pathways linked to inflammation, apoptosis, and angiogenesis. This hydrogel accelerated diabetic wound closure in a rat model in vivo and enhanced collagen deposition, granulation tissue formation, and neovascularization. Furthermore, the hydrogel mitigated oxidative stress and cellular senescence and promoted tissue remodelling. The synergistic effects of PNS and IGF-1 within the hydrogel established a pro-regenerative microenvironment to address both pathological ageing and vascular dysfunction. These findings highlight GelMA/PNS/Alg@IGF-1 as a promising therapeutic platform for diabetic wound management, as this material offers dual anti-senescence and proangiogenic efficacy to overcome the complexities of chronic wound healing.

Atherosclerosis (AS) is a major cause of cardiovascular disease and is characterized by high levels of reactive oxygen species (ROS) and lipid deposition. This study utilized ROS-responsive oxalate bonds to conjugate simvastatin (SV) and tertiary amine-oxide zwitterionic polymer (OPDH), resulting in the design of a ROS-responsive simvastatin nano-prodrug (OPDH-SV). In vitro experiments have proved that OPDH-SV has excellent stability and low toxicity, can effectively reduce intracellular ROS and lipid levels, and inhibit foam cells formation. In addition, OPDH-SV is able to achieve cell-to-cell transmission through the cell's "endocytosis-efflux" mechanism and target mitochondria. In vivo experiments further confirmed the long-term circulation, targeted enrichment, and reduction of ROS and lipid levels of OPDH-SV in vivo. In summary, OPDH-SV has good biosafety and excellent in vivo therapeutic effect, and is expected to become a new type of anti-atherosclerotic nano-prodrug.