1.Application of self-assembly in polypeptide drugs: a review.
Yue WANG ; Xiufang DING ; Sida ZHANG ; Ruihua ZHANG ; Dong CHEN ; Jianfu XU ; Long CHEN
Chinese Journal of Biotechnology 2023;39(1):177-191
Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.
Pharmaceutical Preparations
;
Peptides/chemistry*
;
Amino Acid Sequence
;
Nanostructures/chemistry*
;
Drug Delivery Systems
2.Advances in targeted delivery of proteolysis targeting chimeras in cancer therapy.
Xiaobo WU ; Jie ZHAO ; Yuan GAO ; Qingxin YAO ; Jianjun XIE
Chinese Journal of Biotechnology 2023;39(9):3628-3643
Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.
Humans
;
Proteolysis Targeting Chimera
;
Nanostructures
;
Neoplasms/drug therapy*
;
Proteolysis
3.Regulation of pH on inflation and deflation of biosynthetic gas vesicles used as ultrasound molecular imaging probes.
Yuxiang GONG ; Huan LONG ; Kaiyao HUANG
Chinese Journal of Biotechnology 2023;39(10):4308-4321
Gas vesicles (GVs) are gas-filled protein nanostructures that can regulate the buoyancy of microorganisms such as cyanobacteria and archaea. Recent studies have shown that GVs have the potential to be used as ultrasound molecular imaging probes in disease diagnosis and treatment. However, the mechanism of the inflation and deflation of GVs remains unclear, which hampers the preservation of GVs and gas replacement. In the present study, the environmental pH value was found to be an important factor in regulating the inflation and deflation of GVs. It can not only regulate the inflation and deflation of GVs in vivo to make Microcystis sp. cells present distinct levitation state, but also regulate the inflation and deflation of purified GVs in vitro, and the regulation process is reversible. Our results may provide a technical support for the large-scale production and preservation of biosynthetic ultrasound molecular imaging probes, especially for gas replacement to meet different diagnostic and therapeutic needs, and would facilitate the application of biosynthetic ultrasound molecular imaging probes.
Cyanobacteria
;
Proteins/chemistry*
;
Nanostructures/chemistry*
;
Molecular Imaging
;
Hydrogen-Ion Concentration
4.Direct Synthesis of Bienzyme-like Carbide-derived Carbons via Mild Electrochemical Oxidation of Ti 3AlC 2 MAX.
Yan Feng FANG ; Xiao Teng DING ; Geng Fang XU ; Shi Da GONG ; Yu Sheng NIU ; Zi Yu YAO ; Zhao Yong JIN ; Yao WANG ; Yuan Hong XU
Biomedical and Environmental Sciences 2022;35(3):215-224
Objective:
To develop effective alternatives to natural enzymes, it is crucial to develop nanozymes that are economical, resource efficient, and environmentally conscious. Carbon nanomaterials that have enzyme-like activities have been extensively developed as substitutes for traditional enzymes.
Methods:
Carbide-derived carbons (CDCs) were directly synthesized via a one-step electrochemical method from a MAX precursor using an ammonium bifluoride electrolyte at ambient conditions. The CDCs were characterized by systematic techniques.
Results:
CDCs showed bienzyme-like activities similar to that of peroxidase and superoxide dismutase. We systematically studied the dependence of CDC enzyme-like activity on different electrolytes and electrolysis times to confirm activity dependence on CDC content. Additionally, the synthesis mechanism and CDC applicability were elaborated and demonstrated, respectively.
Conclusion
The demonstrated synthesis strategy eliminates tedious intercalation and delamination centrifugation steps and avoids using high concentrations of HF, high temperatures, and halogen gases. This study paves the way for designing two-dimensional material-based nanocatalysts for nanoenzyme and other applications.
Ammonium Compounds/chemical synthesis*
;
Carbon/chemistry*
;
Electrochemical Techniques
;
Enzymes
;
Fluorides/chemical synthesis*
;
Humans
;
Nanostructures
;
Oxidation-Reduction
5.Peptide-based bioactivated in vivo assembly nanomaterials and its biomedical applications: a review.
Ruxiang LI ; Han REN ; Xiumei LIU ; Zhijian CHEN ; Lili LI ; Hao WANG
Chinese Journal of Biotechnology 2022;38(2):650-665
Based on the self-assembly process occurring in the human body all the time, self-assembled nanomaterials were designed by the researchers. The self-assembled nanomaterials have controllability, biocompatibility and functional advantages in vivo. The self-assembled nanomaterials constructed in situ under a physiological environment display various biological characteristics which can be used for imaging, therapy, and broad clinical applications. In situ self-assembled nanomaterials can boost drug function, reduce toxic and side effects, prolong imaging time and enlarge signal-to-noise ratio. By using pathological conditions to trigger specific responses in vivo, well-ordered nanoaggregates can be spontaneously formed by multiple weak bonding interactions. The assembly shows higher accumulation and longer retention in situ. Endogenous triggers for in situ assembly, such as enzymes, pH, reactive oxygen species and ligand receptor interaction, can be used to transform the materials into a variety of controllable nanostructures including nanoparticles, nanofibers and gels through bioactivated in vivo assembly (BIVA) strategies. BIVA strategies can be applied for treatment, imaging or participate in the physiological activities of cells at the lesion site. This review summarized and prospected the design of self-assembled peptide materials based on BIVA technology and their biomedical applications. The nanostructures of the self-assembly enable some beneficial biological effects, such as assembly induced retention (AIR) effect, enhanced targeting effect, multivalent bond effect, and membrane disturbance. Thus, the BIVA nanotechnology is promising for efficient drug delivery, enhancement of targeting and treatment, as well as optimization of the biological distribution of drugs.
Drug Delivery Systems
;
Humans
;
Nanofibers/chemistry*
;
Nanoparticles
;
Nanostructures/chemistry*
;
Peptides
6.Formulation optimization of emodin nanostructured lipid carriers by Box-Behnken response surface method and in vitro quality evaluation.
De-En HAN ; Yu-Feng XIN ; Heng-Chao WEI ; Xia-Li ZHU ; Ya-Min LIU ; Ping TIAN
China Journal of Chinese Materia Medica 2022;47(4):913-921
Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
Drug Carriers
;
Emodin
;
Follow-Up Studies
;
Lipids
;
Nanostructures
7.Research progress about photothermal nanomaterials with targeted antibacterial properties and their applications in wound healing.
Xiangnan YUAN ; Shaojie TAN ; Jing GAO ; Lu WANG
Journal of Biomedical Engineering 2022;39(1):207-216
With the development of photothermal nanomaterials, photothermal therapy based on near-infrared light excitation shows great potential for the bacterial infected wound treatment. At the same time, in order to improve the photothermal antibacterial effect of wound infection and reduce the damage of high temperature and heat to healthy tissue, the targeted bacteria strategy has been gradually applied in wound photothermal therapy. In this paper, several commonly used photothermal nanomaterials as well as their targeted bacterial strategies were introduced, and then their applications in photothermal antibacterial therapy, especially in bacterial infected wounds were described. Besides, the challenges of targeted photothermal antibacterial therapy in the wound healing application were analyzed, and the development of photothermal materials with targeted antibacterial property has prospected in order to provide a new idea for wound photothermal therapy.
Anti-Bacterial Agents/pharmacology*
;
Humans
;
Nanostructures/therapeutic use*
;
Staphylococcus aureus
;
Wound Healing
;
Wound Infection/therapy*
8.Preparation and catalytic properties of catalase-inorganic hybrid nanoflowers.
Jiao PANG ; Mengtong JIANG ; Yuxin LIU ; Mingyu LI ; Jiaming SUN ; Conggang WANG ; Xianzhen LI
Chinese Journal of Biotechnology 2022;38(12):4705-4718
Catalase is widely used in the food, medical, and textile industries. It possesses exceptional properties including high catalytic efficiency, high specificity, and environmental friendliness. Free catalase cannot be recycled and reused in industry, resulting in a costly industrial biotransformation process if catalase is used as a core ingredient. Developing a simple, mild, cost-effective, and environmentally friendly approach to immobilize catalase is anticipated to improve its utilization efficiency and enzymatic performance. In this study, the catalase KatA derived from Bacillus subtilis 168 was expressed in Escherichia coli. Following separation and purification, the purified enzyme was prepared as an immobilized enzyme in the form of enzyme-inorganic hybrid nanoflowers, and the enzymatic properties were investigated. The results indicated that the purified KatA was obtained through a three-step procedure that included ethanol precipitation, DEAE anion exchange chromatography, and hydrophobic chromatography. Then, by optimizing the process parameters, a novel KatA/Ca3(PO4)2 hybrid nanoflower was developed. The optimum reaction temperature of the free KatA was determined to be 35 ℃, the optimum reaction temperature of KatA/Ca3(PO4)2 hybrid nanoflowers was 30-35 ℃, and the optimum reaction pH of both was 11.0. The free KatA and KatA/Ca3(PO4)2 hybrid nanoflowers exhibited excellent stability at pH 4.0-11.0 and 25-50 ℃. The KatA/Ca3(PO4)2 hybrid nanoflowers demonstrated increased storage stability than that of the free KatA, maintaining 82% of the original enzymatic activity after 14 d of storage at 4 ℃, whereas the free KatA has only 50% of the original enzymatic activity. In addition, after 5 catalytic reactions, the nanoflower still maintained 55% of its initial enzymatic activity, indicating that it has good operational stability. The Km of the free KatA to the substrate hydrogen peroxide was (8.80±0.42) mmol/L, and the kcat/Km was (13 151.53± 299.19) L/(mmol·s). The Km of the KatA/Ca3(PO4)2 hybrid nanoflowers was (32.75±2.96) mmol/L, and the kcat/Km was (4 550.67±107.51) L/(mmol·s). Compared to the free KatA, the affinity of KatA/Ca3(PO4)2 hybrid nanoflowers to the substrate hydrogen peroxide was decreased, and the catalytic efficiency was also decreased. In summary, this study developed KatA/Ca3(PO4)2 hybrid nanoflowers using Ca2+ as a self-assembly inducer, which enhanced the enzymatic properties and will facilitate the environmentally friendly preparation and widespread application of immobilized catalase.
Catalase
;
Nanostructures/chemistry*
;
Hydrogen Peroxide/metabolism*
;
Enzymes, Immobilized/chemistry*
;
Catalysis
9.Role of biomimetic nanomaterials made from glioma cell- derived extracellular vesicles in targeted delivery of STAT3-siRNA.
Dun HU ; Xin LI ; Shengdan NIE ; Shan WANG
Journal of Central South University(Medical Sciences) 2022;47(12):1646-1654
OBJECTIVES:
Glioma is the most common primary intracranial tumor and there is still no ideal treatment at present. Gene therapy, as one of the new methods for treating glioma, has attracted attention in recent years. But its application in treating glioma is very limited due to lack of effective delivery vectors. This study aims to investigate the feasibility of biomimetic nanomaterials made from glioma cells-derived extracellular vesicles (EV) for targeted delivery of signal transducers and activators of transcription 3 (STAT3)-small interfering RNA (siRNA) in treating glioma.
METHODS:
First, U251 glioma cells-derived extracellular vessel (EVU251) was extracted by ultra-centrifugal method. Nanoparticle tracking analysis was used to characterize the particle size distribution, the transmission electron microscope was used to analyze the morphology, and Western blotting was used to verify the expression of srface characteristic protein. The homing ability was verified by cell uptake assay after labeling EVU251 with membrane dye kit PKH67; the EVU251 contents were removed by a low permeability method and then EVMU251 was prepared through a microporous membrane. Finally, the biomimetic nanomaterials EVMU251@STAT3-siRNA were prepared by loading STAT3-SiRNA with electro-dyeing method. The real-time quantitative PCR was used to quantify the successful encapsulation of siRNA, and the encapsulation and drug loading rate was calculated; then Cy5-labeled siRNA was used to evaluate the ability of biomimetic nanomaterials (EVMU251@CY5-siRNA) to target U251 cells. Lysosomal escape ability of the biomimetic nanomaterial was evaluated by lysosomal dye lyso-tracker green. At last, the ability of EVMU251@STAT3-siRNA to knock down STAT3 gene and selective killing of U251 cells was detected by cell experiments in vitro.
RESULTS:
The size of EVU251 ranged from 50 nm to 200 nm with a natural disc shape. The expression of extracellular vesicle marker proteins could be detected on the membrane of EVU251. The cell uptake assay demonstrated that it had homing ability to target U251 cells. After EVU251 was prepared as EVMU251@STAT3-siRNA, the particle size was (177.9±5.0) nm, the siRNA loading rate was (33.5±2.2)% and the drug loading rate was (3.24±0.21)%. The biomimetic nanomaterial EVMU251@STAT3-siRNA still had the ability to target U251 cells and successfully deliver siRNA to the cytoplasm without lysosomal degradation. The EVMU251@STAT3-siRNA can effectively knock down the expression of STAT3 gene and produce selective killing ability in U251 cells.
CONCLUSIONS
The biomimetic nanomaterials EVMU251@STAT3-siRNA made from glioma U251 cells-derived extracellular vesicles can knock down STAT3 gene of U251 cells and produce selective killing effect, which can provide a new idea for the treatment of glioma.
Humans
;
RNA, Small Interfering/genetics*
;
Biomimetics
;
Cell Line, Tumor
;
Glioma/therapy*
;
Nanostructures
;
Cell Proliferation
;
STAT3 Transcription Factor/metabolism*
10.Bio-based molecules for biosynthesis of nano-metallic materials.
Yan FANG ; Lingling FAN ; Huiyu BAI ; Binrui LI ; Haowei ZHANG ; Fengxue XIN ; Jiangfeng MA ; Min JIANG
Chinese Journal of Biotechnology 2021;37(2):541-560
Nano-metallic materials are playing an important role in the application of medicine, catalysis, antibacterial and anti-toxin due to their obvious advantages, including nanocrystalline strengthening effect, high photo-absorptivity, high surface energy and single magnetic region performance. In recent years, with the increasing consumption of global petrochemical resources and the aggravation of environmental pollution, nanomaterials based on bio-based molecules have aroused great concern. Bio-based molecules refer to small molecules and macromolecules directly or indirectly derived from biomass. They usually have good biocompatibility, low toxicity, degradability, wide source and low price. Besides, most bio-based molecules have unique physical, chemical properties and physiological activity, such as optical activity, acid/alkali amphoteric property, hydrophilic property and easy coordination with metal ions. Thus, the corresponding nano-materials based on bio-based molecules also have unique functions, such as anti-inflammatory, anti-cancer, anti-oxidation, antiviral fall blood sugar and blood fat etc. In this paper, we give a comprehensive overview of the preparation and application of nano-metallic materials based on bio-based molecules in recent years.
Anti-Infective Agents
;
Catalysis
;
Metals
;
Nanostructures

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