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.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
3.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
4.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
5.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
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Nanostructures/chemistry*
;
Hydrogen Peroxide/metabolism*
;
Enzymes, Immobilized/chemistry*
;
Catalysis
6.Platelet membrane-based and tumor-associated platelettargeted drug delivery systems for cancer therapy.
Yinlong ZHANG ; Guangna LIU ; Jingyan WEI ; Guangjun NIE
Frontiers of Medicine 2018;12(6):667-677
Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.
Animals
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Antineoplastic Agents
;
chemistry
;
pharmacology
;
Biomimetic Materials
;
chemistry
;
Blood Platelets
;
cytology
;
Drug Carriers
;
chemistry
;
Humans
;
Models, Animal
;
Nanomedicine
;
methods
;
Nanostructures
;
chemistry
;
Neoplasms
;
drug therapy
7.Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism.
Sensen ZHANG ; Ningning LI ; Wenwen ZENG ; Ning GAO ; Maojun YANG
Protein & Cell 2017;8(11):834-847
TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a "move upward" motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.
Animals
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Calcium
;
metabolism
;
Cryoelectron Microscopy
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Endocytosis
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Endosomes
;
metabolism
;
Gene Expression
;
HEK293 Cells
;
Humans
;
Hydrogen-Ion Concentration
;
Lysosomes
;
metabolism
;
Mice
;
Models, Biological
;
Mucolipidoses
;
genetics
;
metabolism
;
pathology
;
Nanostructures
;
chemistry
;
ultrastructure
;
Phosphatidylinositols
;
metabolism
;
Transgenes
;
Transient Receptor Potential Channels
;
chemistry
;
genetics
;
metabolism
8.Recent advances and perspective in the study of the nano-reinforcing materials for molecular imprinting of proteins.
Zhi-hui WU ; Miao-ling CHAI ; Jia-peng HOU ; Jun PAN
Acta Pharmaceutica Sinica 2015;50(1):15-20
Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. This review, we summarized the research findings over the past years, and discussed the nano-reinforcing materials used to prepare molecular imprinting of proteins and the perspective of these nano-reinforcing materials.
Binding Sites
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Molecular Conformation
;
Molecular Imprinting
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Nanostructures
;
chemistry
;
Polymers
;
chemistry
;
Proteins
;
chemistry
9.Nanostructured lipid carrier based topical gel of Ganoderma Triterpenoids for frostbite treatment.
Cheng-Ying SHEN ; Ling DAI ; Bao-De SHEN ; Xu ZHOU ; Jin-Xia BAI ; He XU ; Qing-Yuan LV ; Jin HAN ; Hai-Long YUAN
Chinese Journal of Natural Medicines (English Ed.) 2015;13(6):454-460
The objective of this study was to prepare nanostructured lipid carrier (NLC)-based topical gel of Ganoderma Triterpenoids (GTs) and evaluate their effects on frostbite treatment. GT-NLCs was prepared by the high pressure homogenization method and then characterized by morphology and analyses of particle size, zeta potential, entrapment efficiency (EE), and drug loading (DL). The NLCs was suitably gelled for skin permeation studies in vitro and pharmacodynamic evaluation in vivo, compared with the GT emulgel. The GT-NLC remained within the colloidal range and was uniformly dispersed after suitably gelled by carbopol preparation. Transmission electron microscopy (TEM) study showed GT-NLCs was spherical in shape. The EE (%) and DL (%) could reach up to (81.84 ± 0.60)% and (2.13 ± 0.12)%, respectively. The result of X-ray diffractograms (XRD) showed that GTs were in an amorphous state in the NLC-gel. In vitro permeation studies through rat skin indicated that the amount of GTs permeated through skin of GT-NLCs after 24 h was higher than that of GT emulsion, and GT-NLCs increased the accumulative amounts of GTs in epidermis 7.76 times greater than GT emulsion. GT-NLC-gel was found to possess superior therapeutic effect for frostbite, compared with the GT emulgel. The NLC based topical gel of GTs could improve -their therapeutic effect for frostbite.
Animals
;
Drug Carriers
;
chemistry
;
Drugs, Chinese Herbal
;
administration & dosage
;
chemistry
;
Frostbite
;
drug therapy
;
Ganoderma
;
chemistry
;
Gels
;
administration & dosage
;
chemistry
;
Humans
;
Lipids
;
chemistry
;
Male
;
Nanostructures
;
administration & dosage
;
chemistry
;
Rats
;
Rats, Sprague-Dawley
10.The progress of magnetic nanomaterials in application of biomedicine.
Journal of Biomedical Engineering 2014;31(2):472-476
Magnetic nanomaterials is widely used in medical diagnosis, drug delivery, biomedical and other fields due to their unique structure and excellent properties. The magnetic nanometer material in biomedical applications, such as biological separation and purification, application of controlled drug release and magnetic resonance imaging are reviewed in the present paper, and the development trend of magnetic nanomaterials is also forecasted.
Drug Delivery Systems
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Humans
;
Magnetic Resonance Imaging
;
Magnetics
;
Nanostructures
;
chemistry

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