Silver nanoparticles of Albizia adianthifolia: the induction of apoptosis in human lung carcinoma cell lineJournal of Nanobiotechnology - Tập 11 Số 1 - 2013
Rishalan Govender, Alisa Phulukdaree, Robert Moonsamy Gengan, Krishnan Anand, Anil A. Chuturgoon
AbstractBackgroundSilver nanoparticles (AgNP), the most popular nano-compounds, possess unique properties.Albizia adianthifolia(AA) is a plant of the Fabaceae family that is rich in saponins. The biological properties of a novel AgNP, synthesized from an aqueous leaf extract of AA (AAAgNP), were investigated on A549 lung cells. Cell viability was determined by the MTT assay. Cellular oxidative status (lipid peroxidation and glutathione (GSH) levels), ATP concentration, caspase-3/-7, -8 and −9 activities were determined. Apoptosis, mitochondrial (mt) membrane depolarization (flow cytometry) and DNA fragmentation (comet assay) were assessed. The expression of CD95 receptors, p53, bax, PARP-1 and smac/DIABLO was evaluated by flow cytometry and/or western blotting.
ResultsSilver nanoparticles of AA caused a dose-dependent decrease in cell viability with a significant increase in lipid peroxidation (5-fold vs. control;p = 0.0098) and decreased intracellular GSH (p = 0.1184). A significant 2.5-fold decrease in cellular ATP was observed upon AAAgNPexposure (p = 0.0040) with a highly significant elevation in mt depolarization (3.3-fold vs. control;p < 0.0001). Apoptosis was also significantly higher (1.5-fold) in AAAgNPtreated cells (p < 0.0001) with a significant decline in expression of CD95 receptors (p = 0.0416). Silver nanoparticles of AA caused a significant 2.5-fold reduction in caspase-8 activity (p = 0.0024) with contrasting increases in caspase-3/-7 (1.7-fold vs. control;p = 0.0180) and −9 activity (1.4-fold vs. control;p = 0.0117). Western blots showed increased expression of smac/DIABLO (4.1-fold) in treated cells (p = 0.0033). Furthermore, AAAgNPsignificantly increased the expression of p53, bax and PARP-1 (1.2-fold;p = 0.0498, 1.6-fold;p = 0.0083 and 1.1-fold;p = 0.0359 respectively).
ConclusionData suggests that AAAgNPinduces cell death in the A549 lung cells via the mt mediated intrinsic apoptotic program. Further investigation is required to potentiate the use of this novel compound in cancer therapy trials.
Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonistJournal of Nanobiotechnology -
Zijian Su, Hongjie Zhang, Jieqiong Cao, Yuanmeng Sun, Yuling Cai, Bihui Zhang, He Liu, Zilei Zhang, Jianwen Xie, Qilin Meng, Lin Luo, Fu Li, Jingsheng Li, Jin‐Ting Zhang, Xiaojia Chen, Hongyu An
AbstractAcne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.
Graphical Abstract
Nanomechanical properties of enucleated cells: contribution of the nucleus to the passive cell mechanicsJournal of Nanobiotechnology - - 2020
Yuri Efremov, Svetlana Kotova, А. А. Акованцева, Peter Timashev
Abstract
Background
The nucleus, besides its functions in the gene maintenance and regulation, plays a significant role in the cell mechanosensitivity and mechanotransduction. It is the largest cellular organelle that is often considered as the stiffest cell part as well. Interestingly, the previous studies have revealed that the nucleus might be dispensable for some of the cell properties, like polarization and 1D and 2D migration. Here, we studied how the nanomechanical properties of cells, as measured using nanomechanical mapping by atomic force microscopy (AFM), were affected by the removal of the nucleus.
Methods
The mass enucleation procedure was employed to obtain cytoplasts (enucleated cells) and nucleoplasts (nuclei surrounded by plasma membrane) of two cell lines, REF52 fibroblasts and HT1080 fibrosarcoma cells. High-resolution viscoelastic mapping by AFM was performed to compare the mechanical properties of normal cells, cytoplasts, and nucleoplast. The absence or presence of the nucleus was confirmed with fluorescence microscopy, and the actin cytoskeleton structure was assessed with confocal microscopy.
Results
Surprisingly, we did not find the softening of cytoplasts relative to normal cells, and even some degree of stiffening was discovered. Nucleoplasts, as well as the nuclei isolated from cells using a detergent, were substantially softer than both the cytoplasts and normal cells.
Conclusions
The cell can maintain its mechanical properties without the nucleus. Together, the obtained data indicate the dominating role of the actomyosin cytoskeleton over the nucleus in the cell mechanics at small deformations inflicted by AFM.
Nanomaterial enabled sensors for environmental contaminantsJournal of Nanobiotechnology - Tập 16 - Trang 1-16 - 2018
Marjorie R. Willner, Peter J. Vikesland
The need and desire to understand the environment, especially the quality of one’s local water and air, has continued to expand with the emergence of the digital age. The bottleneck in understanding the environment has switched from being able to store all of the data collected to collecting enough data on a broad range of contaminants of environmental concern. Nanomaterial enabled sensors represent a suite of technologies developed over the last 15 years for the highly specific and sensitive detection of environmental contaminants. With the promise of facile, low cost, field-deployable technology, the ability to quantitatively understand nature in a systematic way will soon be a reality. In this review, we first introduce nanosensor design before exploring the application of nanosensors for the detection of three classes of environmental contaminants: pesticides, heavy metals, and pathogens.
A thermoreversible antibacterial zeolite-based nanoparticles loaded hydrogel promotes diabetic wound healing via detrimental factor neutralization and ROS scavengingJournal of Nanobiotechnology - Tập 19 - Trang 1-20 - 2021
Yao Qi, Kun Qian, Jin Chen, Yifeng E, Yijie Shi, Hongdan Li, Liang Zhao
As recovery time of diabetic wound injury is prolonged by the production of detrimental factors, including reactive oxygen species (ROS) and inflammatory cytokines, attenuating the oxidative stress and inflammatory reactions in the microenvironment of the diabetic wound site would be significant. In our study, we prepared thermoreversible, antibacterial zeolite-based nanoparticles loaded hydrogel to promote diabetic wound healing via the neutralization of detrimental factors such as inflammatory cytokines and ROS. The cerium (Ce)-doped biotype Linde type A (LTA) zeolite nanoparticles synergistically eliminated mitochondrial ROS and neutralized free inflammatory factors, thus remodeling the anti-inflammatory microenvironment of the wound and enhancing angiogenesis. Moreover, the thermoreversible hydrogel composed of Pluronic F127 and chitosan demonstrated strong haemostatic and bactericidal behavior. In conclusion, the obtained thermoreversible, antibacterial, zeolite-based nanoparticles loaded hydrogels represent a multi-targeted combination therapy for diabetic wound healing.
Development of multivalent nanobodies blocking SARS-CoV-2 infection by targeting RBD of spike proteinJournal of Nanobiotechnology - Tập 19 - Trang 1-12 - 2021
Qizhong Lu, Zongliang Zhang, Hexian Li, Kunhong Zhong, Qin Zhao, Zeng Wang, Zhiguo Wu, Donghui Yang, Shuang Sun, Nian Yang, Meijun Zheng, Qiang Chen, Cheng Long, Wenhao Guo, Hui Yang, Chunlai Nie, Aiping Tong
The outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein were developed. Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91-hFc and Nb3-hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91-Nb3-hFc exhibited the strongest RBD-binding affinity and neutralizing ability against SARS-CoV-2 pseudoviruses with an IC50 value at approximately 1.54 nM. The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91-Nb3-hFc may serve as a potential therapeutic agent for the treatment of COVID-19.
Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatmentJournal of Nanobiotechnology - Tập 21 - Trang 1-19 - 2023
Lu Lu, Lingli Quan, Jian Li, Junbin Yuan, Xinmin Nie, Xueyuan Huang, Hang Dong, Yanrong Su, Yufen Huang, Qingjie Kou, Leping Liu, Haiting Liu, Xionghui Zhou, Rong Gui, Lan Gu
Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.
Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapyJournal of Nanobiotechnology - Tập 19 - Trang 1-14 - 2021
Xiaoyan Wang, Ming Wu, Xiaolong Zhang, Feida Li, Yongyi Zeng, Xinyi Lin, Xiaolong Liu, Jingfeng Liu
Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy. The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo. BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.
Antioxidant capacities of the selenium nanoparticles stabilized by chitosanJournal of Nanobiotechnology - Tập 15 - Trang 1-12 - 2017
Xiaona Zhai, Chunyue Zhang, Guanghua Zhao, Serge Stoll, Fazheng Ren, Xiaojing Leng
Selenium (Se) as one of the essential trace elements for human plays an important role in the oxidation reduction system. But the high toxicity of Se limits its application. In this case, the element Se with zero oxidation state (Se0) has captured our attention because of its low toxicity and excellent bioavailability. However, Se0 is very unstable and easily changes into the inactive form. By now many efforts have been done to protect its stability. And this work was conducted to explore the antioxidant capacities of the stable Se0 nanoparticles (SeNPs) stabilized using chitosan (CS) with different molecular weights (Mws) (CS-SeNPs). The different Mws CS-SeNPs could form uniform sphere particles with a size of about 103 nm after 30 days. The antioxidant tests of the DPPH, ABTS, and lipid peroxide models showed that these CS-SeNPs could scavenge free radicals at different levels. And the 1 month old SeNPs held the higher ABTS scavenging ability that the value could reach up to 87.45 ± 7.63% and 89.44 ± 5.03% of CS(l)-SeNPs and CS(h)-SeNPs, respectively. In the cell test using BABLC-3T3 or Caco-2, the production of the intracellular reactive oxygen species (ROS) could be inhibited in a Se concentration-dependent manner. The topical or oral administration of CS-SeNPs, particularly the Se nanoparticles stabilized with low molecular weight CS, CS(l)-SeNPs, and treated with a 30-day storage process, could efficiently protect glutathione peroxidase (GPx) activity and prevent the lipofusin formation induced by UV-radiation or d-galactose in mice, respectively. Such effects were more evident in viscera than in skin. The acute toxicity of CS(l)-SeNPs was tenfold lower than that of H2SeO3. Our work could demonstrate the CS-SeNPs hold a lower toxicity and a 30-day storage process could enhance the antioxidant capacities. All CS-SeNPs could penetrate the tissues and perform their antioxidant effects, especially the CS(l)-SeNPs in mice models. What’s more, the antioxidant capacities of CS-SeNPs were more evident in viscera than in skin.
Emerging nanobiotechnology for precise theranostics of hepatocellular carcinomaJournal of Nanobiotechnology - Tập 20 - Trang 1-21 - 2022
Mengjiao Xu, Liu Yang, Yanjie Lin, Yao Lu, Xiaoyue Bi, Tingting Jiang, Wen Deng, Lu Zhang, Wei Yi, Yao Xie, Minghui Li
Primary liver cancer has become the second most fatal cancer in the world, and its five-year survival rate is only 10%. Most patients are in the middle and advanced stages at the time of diagnosis, losing the opportunity for radical treatment. Liver cancer is not sensitive to chemotherapy or radiotherapy. At present, conventional molecularly targeted drugs for liver cancer show some problems, such as short residence time, poor drug enrichment, and drug resistance. Therefore, developing new diagnosis and treatment methods to effectively improve the diagnosis, treatment, and long-term prognosis of liver cancer is urgent. As an emerging discipline, nanobiotechnology, based on safe, stable, and efficient nanomaterials, constructs highly targeted nanocarriers according to the unique characteristics of tumors and further derives a variety of efficient diagnosis and treatment methods based on this transport system, providing a new method for the accurate diagnosis and treatment of liver cancer. This paper aims to summarize the latest progress in this field according to existing research and the latest clinical diagnosis and treatment guidelines in hepatocellular carcinoma (HCC), as well as clarify the role, application limitations, and prospects of research on nanomaterials and the development and application of nanotechnology in the diagnosis and treatment of HCC.
