Pathway-Dependent Preferential Selection and Amplification of Variable Self-Assembled Peptide Nanostructures and Their Biological Activities

2020 ◽  
Vol 12 (47) ◽  
pp. 52445-52456
Author(s):  
Harsimran Kaur ◽  
Rashmi Jain ◽  
Sangita Roy

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Guo ◽  
Yongshun Song ◽  
Yujiao Wang ◽  
Tingyuan Tan ◽  
Yuwen Ji ◽  
...  

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures.



2021 ◽  
Author(s):  
Zhuomin Xu ◽  
Shanshan Zheng ◽  
Yulu Hong ◽  
Yue Cai ◽  
Qiuqin Zhang ◽  
...  

Abstract Background: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy.Results: CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was -11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about 2 time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth.Conclusions: Na2GA/CA-BM nanoparticles (131.6 nm, -11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.



2020 ◽  
Author(s):  
Kaili Zhao ◽  
Ruirui Xing ◽  
Xuehai Yan


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhuomin Xu ◽  
Shanshan Zheng ◽  
Xin Gao ◽  
Yulu Hong ◽  
Yue Cai ◽  
...  

Abstract Background Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy. Results CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was − 11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about two time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth. Conclusions Na2GA/CA-BM nanoparticles (131.6 nm, − 11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment. Graphic abstract



2021 ◽  
Vol 13 (37) ◽  
pp. 44065-44078
Author(s):  
Ziying Li ◽  
Yilin Zheng ◽  
Huifang Shi ◽  
Huanzhang Xie ◽  
Ya Yang ◽  
...  


Author(s):  
Huimin Wang ◽  
Hong Deng ◽  
Menghan Gao ◽  
Weiqi Zhang

The polysaccharides (PS) have been widely used as biomaterials in drug delivery, due to their excellent biocompatibility, ease of functionalization, and intrinsic biological activities. Among the various PS-based biomaterials, the self-assembled PS nanogels (NG) featuring facile preparation are attracting evergrowing interests in various biomedical applications. Specifically, NG derived from the self-assembly of natural PS well maintain both the physicochemical and biological properties of PS while avoiding the chemical modification or alteration of PS structure, representing a potent drug delivery system for various therapeutic agents. In this review, the natural PS, such as chitosan, alginate, and hyaluronan, for self-assembled NG construction and their advantages in the applications of drug delivery have been summarized. The residues, such as amine, carboxyl, and hydroxyl groups, on these PS provide multiple sites for both ionic cross-linking and metal coordination, which greatly contribute to the formation of self-assembled NG as well as the drug loading, thus enabling a wide biomedical application of PS NG, especially for drug delivery. Future developments and considerations in the clinical translation of these self-assembled PS NG have also been discussed.





Author(s):  
Rashmi C. Desai ◽  
Raymond Kapral


2017 ◽  
Vol 87 (3-4) ◽  
pp. 191-200 ◽  
Author(s):  
Nidhal Soualeh ◽  
Aliçia Stiévenard ◽  
Elie Baudelaire ◽  
Rachid Soulimani ◽  
Jaouad Bouayed

Abstract. In this study, cytoprotective and antioxidant activities of Rosa canina (RC) and Salix alba (SA), medicinal plants, were studied on mouse primary splenocytes by comparing Controlled Differential Sieving process (CDSp), which is a novel green solvent-free process, versus a conventional technique, employing hydroethanolic extraction (HEE). Thus, preventive antioxidant activity of three plant powders of homogeneous particle sizes, 50–100 µm, 100–180 µm and 180–315 µm, dissolved directly in the cellular buffer, were compared to those of hydroethanolic (HE) extract, at 2 concentrations (250 and 500 µg/mL) in H2O2-treated spleen cells. Overall, compared to HE extract, the superfine powders, i. e., fractions < 180 µm, at the lowest concentration, resulted in greater reactive oxygen species (ROS) elimination, increased glutathione peroxidase (GPx) activity and lower malondialdehyde (MDA) production. Better antioxidant and preventive effects in pre-treated cells were found with the superfine powders for SA (i. e., 50–100 µm and 100–180 µm, both p < 0.001), and with the intermediate powder for RC (i. e., 100–180 µm, p < 0.05) versus HE extract. The activity levels of catalase (CAT) and superoxide dismutase (SOD) in pretreated splenocytes exposed to H2O2, albeit reduced, were near to those in unexposed cells, suggesting that pretreatment with the fine powders has relatively restored the normal levels of antioxidant-related enzymes. These findings supported that CDSp improved the biological activities of plants, avoiding the use of organic solvents and thus it could be a good alternative to conventional extraction techniques.



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