Immobilization of PR4A3 enzyme in pluronic F127 polymeric micelles against colorectal adenocarcinoma cells and increase of in vitro bioavailability.

Published on Jan 1, 2021in International Journal of Biological Macromolecules5.162
· DOI :10.1016/J.IJBIOMAC.2020.11.006
Natielle Cachoeira Dotivo2
Estimated H-index: 2
(UCSC: University of California, Santa Cruz),
Rachel Passos Rezende16
Estimated H-index: 16
(UCSC: University of California, Santa Cruz)
+ 8 AuthorsJoão Carlos Teixeira Dias14
Estimated H-index: 14
(UCSC: University of California, Santa Cruz)
Sources
Abstract
Traditional therapy for malignant neoplasms involving surgical procedures, radiotherapy and chemotherapy aims to kill neoplastic cells, but also affects normal cells. Therefore, exogenous proteases are the target of studies in cancer therapy, as they have been shown to be effective in suppressing tumors and reducing metastases. Pluronic F127 (F127) is a copolymer of amphiphilic blocks that has shown significant potential for drug administration, as it is capable of incorporating hydrophobic drugs and self-assembling in micrometers of nanometric size. This study investigated the effects of immobilization of the alkaline protease PR4A3 with pluronic F127 micelles on the enzyme-induced cytotoxicity. Protease immobilization was demonstrated through UV-visible and circular dichroism (CD) spectroscopies, as the enzyme interacts with the polymeric micelle of Pluronic F127 without changing its secondary structure. In addition, the immobilized form of the enzyme showed greater bioavailability after passing through the simulated gastrointestinal transit. Cell viability was assessed using the tetrazoic methylthiazole (MTT) assay. The results open perspectives for new research and development for PR4A3 in the treatment of colorectal carcinoma.
📖 Papers frequently viewed together
30 Citations
88 Citations
References43
Newest
#1Ranjan GangulyH-Index: 31
#2Sugam KumarH-Index: 17
Last. J.S. Melo (BARC: Bhabha Atomic Research Centre)H-Index: 2
view all 10 authors...
Abstract Curcumin, the principle active constituent of turmeric, is known to have broad range of therapeutic properties. Its poor aqueous solubility and low bioavailability however, act as constraints for its biomedical applications. Recent studies have shown that incorporation of curcumin in nano-carriers like micelles, vesicles, polymeric nanoparticles etc. can help in overcoming these issues and improve its therapeutic abilities quite significantly. In this manuscript, we report preparation o...
11 CitationsSource
#1Rosemaire S. S. de Oliveira (UCSC: University of California, Santa Cruz)H-Index: 1
#2Nélida Simona Marin Huachaca (UCSC: University of California, Santa Cruz)H-Index: 2
Last. Luiz C. Salay (UCSC: University of California, Santa Cruz)H-Index: 9
view all 6 authors...
Nanotechnology is important for the development of new materials capable to improve the development of novel drug delivery systems. Such systems may result in more efficient therapeutic effects with reduced toxicity and extended time in the organism and increase in bioavailability, biocompatibility, and solubility of drugs. Here it was investigated the interaction between the triblock copolymer Pluronic F127 (F127) and a natural bioactive amphiphilic saponin (SAP), extracted from Glycyrrhiza gla...
6 CitationsSource
#1Yi Zhao (UNC: University of North Carolina at Chapel Hill)H-Index: 13
#2Daria Y. Alakhova (UNC: University of North Carolina at Chapel Hill)H-Index: 12
Last. Alexander V. Kabanov (MSU: Moscow State University)H-Index: 106
view all 6 authors...
Abstract The potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to th...
17 CitationsSource
#1Tatyana V. Volkova (RAS: Russian Academy of Sciences)H-Index: 16
#2Ekaterina N. Domanina (ISUCT: Ivanovo State University of Chemistry and Technology)H-Index: 1
Last. Irina V. Terekhova (RAS: Russian Academy of Sciences)H-Index: 16
view all 5 authors...
Abstract Solubility and permeability are the main parameters determining the bioavailability of drugs. In this study the increased solubility of novel 1,2,4-thiadiazole derivative (TDZ) proposed for the prevention and treatment of Alzheimer's disease was achieved in the solutions of polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and pluronic F127 (F127). It was found that solubilizing power of polymers follows the order F127 > PVP > PEG. The mechanism of TDZ solubilization was proposed o...
10 CitationsSource
#1Luiz C. Salay (UCSC: University of California, Santa Cruz)H-Index: 9
#2Elielma A. Prazeres (UCSC: University of California, Santa Cruz)H-Index: 1
Last. Eloi Feitosa (UNESP: Sao Paulo State University)H-Index: 24
view all 9 authors...
Triblock copolymers, such as Pluronic F127 (F127), are pharmaceutically important amphiphilic compounds that self-assemble in aqueous solution either as discrete or entangled micelles, depending on their concentration and temperature, which may function as drug delivery vehicle. Herein, we have synthesized the antimicrobial peptide tritrpticin (TRP3), a tryptophan (Trp)- and arginine (Arg)-rich peptide, sequence VRRFPWWWPFLRR, with a broad spectrum of action against bacteria and fungi, to invest...
4 CitationsSource
#1Han Yao (UGent: Ghent University)H-Index: 5
#2Evelien Wynendaele (UGent: Ghent University)H-Index: 18
Last. Bart De Spiegeleer (UGent: Ghent University)H-Index: 30
view all 5 authors...
Abstract Circular dichroism (CD) is a non-destructive and powerful technique for providing structure and ligand interaction information of small molecules as well as biotechnological medicines. While CD is a well-established technique in biomedical research, and different types and variants of CD do exist, the focus of this review is on the pharmaceutical quality control (QC) aspects of the classic electronic CD (ECD). The basic principles of the CD technique are initially described, followed by...
19 CitationsSource
#1Wangsa T. IsmayaH-Index: 9
Last. Heni Rachmawati (ITB: Bandung Institute of Technology)H-Index: 17
view all 9 authors...
Abstract The light subunit of mushroom Agaricus bisporus tyrosinase (LSMT) is a protein of unknown function that was discovered serendipitously during the elucidation of the crystal structure of the enzyme. The protein is non-immunogenic and can penetrate the intestinal epithelial cell barrier, and thus, similar to its structural homologue HA-33 from Clostridium botulinum , may be potentially absorbable by the intestine. LSMT also shares high structural homology with the ricin-B-like lectin from...
16 CitationsSource
#1Tharcilla Braz Alves Pessoa (UEFS: State University of Feira de Santana)H-Index: 3
#2Rachel Passos Rezende (State University of Santa Cruz)
Last. João Carlos Teixeira Dias (UCSC: University of California, Santa Cruz)H-Index: 14
view all 11 authors...
Functional screening of metagenomic libraries is an important tool for the discovery of new molecules. The metabolic diversity of microorganisms enables survival in harsh environments and is related to the production of enzymes. In this study, we identified a protease-producing clone from a metagenomic library derived from mangrove sediment. The protease was purified by ammonium sulphate precipitation and gel filtration chromatography, with a yield of 77.27% and a specific activity of 8.57 U μg−...
12 CitationsSource
#1Yuling Liu (Peking Union Medical College)H-Index: 15
#2Sai FuH-Index: 2
Last. Hui LiH-Index: 12
view all 8 authors...
: Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and T...
29 CitationsSource
#1Xiang-Jun Tang (HUM: Hubei University of Medicine)H-Index: 5
#2Kuanming Huang (HUM: Hubei University of Medicine)H-Index: 5
Last. Gang Wang (Jiangsu University)H-Index: 9
view all 8 authors...
As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viabi...
16 CitationsSource
Cited By0
Newest