Preparation of Strong Antioxidative, Therapeutic Nanoparticles Based on Amino Acid-Induced Ultrafast Assembly of Tea Polyphenols

Abstract

Nanoformulations offer the opportunity to overcome the shortcomings of drug molecules, such as low solubility, side effects, insufficient stability, etc., but in most of the current nanomedicines, nanocarriers as excipients do not directly participate in the therapy procedure. Accordingly, it is promising to develop the nanotherapeutics composed entirely of pharmaceutically active molecules. Tea polyphenols, especially epigallocatechin gallate (EGCG), are a kind of natural antioxidants with various biological and health beneficial effects and are extensively investigated as nutrients and anticancer drugs. Here, the sizetunable and highly active polyphenol nanoparticles were conveniently synthesized in water and could be massively produced with a simple facility. Compared to the previous strategies, either molecular assembly via oxidative coupling or combination with other biomacromolecules, the present preparation was conducted by the amino acid-triggered Mannish condensation reactions, thus permitting the flexible molecular design of various polyphenol nanoparticles by selecting different amino acids. This straightforward and ultrafast method actually opens up a novel means to make use of naturally reproducible polyphenols. Moreover, inheriting the salient properties of EGCG, these nanoparticles show strong antioxidation capacity, 10-fold higher than the extensively investigated polydopamine nanoparticles, and they are biosafe but have therapeutic effects, according to the in vitro and in vivo assessments of anticancer activity, which is promising for various biomedical purposes.

General Nanomedicine Platform by Solvent-Mediated Disassembly/Reassembly of Scalable Natural Polyphenol Colloidal Spheres

“…In our previous work, we reported that high doses of EGCG pure nanocarriers had good antitumor effects in vivo. 32 In this work, the antitumor effect of R-GCS/DOX nanodrugs prepared by the reassembly of polyphenol CSs was also better than that of free DOX, which again proved that catechin can enhance the antitumor ability of the drug, showing the advantages of using therapeutic molecules to construct nanomedicines. As shown in Figure S12, HE sections of heart, liver, lung, and kidney in all groups showed normal tissue structure and no lesions.…”

“…The average weight of the spleen in the control group was 0.77 g, while that in the DOX group was 0.073 g and R-GCS/DOX was 0.059 g (Figure e,f). In our previous work, we reported that high doses of EGCG pure nanocarriers had good antitumor effects in vivo . In this work, the antitumor effect of R-GCS/DOX nanodrugs prepared by the reassembly of polyphenol CSs was also better than that of free DOX, which again proved that catechin can enhance the antitumor ability of the drug, showing the advantages of using therapeutic molecules to construct nanomedicines.…”

“…EGCG has a galloyl moiety at the C-3 position, showing the highest reactivity in the reaction of green tea catechins with formaldehyde among all of the catechins. 36 In the previous study, it has been reported that CCSs were formed by the condensation of polyphenol, aldehyde, and amine, and it is verified that the CCSs were composed of polyphenol oligomer derivatives by NMR, Fourier transform infrared and TOF-MS. 32 As shown in Figure 1a,b, the formation of polyphenolic CSs was mainly through the Mannich reaction of either the glycine (Gly) or cysteine (Cys) system containing EGCG and formaldehyde in aqueous solution at room temperature. There are many hydrophobic (aromatic) and hydrophilic (polyhydroxyls) segments in the molecular structure of EGCG, but their unsuitable ratio limited the well-defined assembly of EGCG.…”

“…The amine-mediated flexible preparation of versatile polyphenol nanoparticles and amino acid-induced ultrafast assembly of strong antioxidative therapeutic tea polyphenol nanoparticles were reported by our group. 31,32 In this paper, EGCG oligomers were synthesized by Mannich condensation of EGCG, aldehydes, and amino acids. These oligomers selfassembled into EGCG colloidal spheres (CSs) by π−π stacking and hydrogen-bonding interaction in aqueous solution.…”

Biocompatible, Antioxidant Nanoparticles Prepared from Natural Renewable Tea Polyphenols and Human Hair Keratins for Cell Protection and Anti-inflammation

“…30% of its dry leaf weight, and also collectively referred to as catechins. The biological bioactivities of TP with epigallocatechin gallate (EGCG) as the primary contributor have been well documented, such as antioxidation, anticancer, inhibiting human stone formation, and reducing the risk of degenerative diseases. − The use of TP or EGCG as the active molecule either for direct encapsulation or for fabricating functional nanomaterials is now a hot theme in the field of nutrition and pharmaceutical science. − The combination of keratin and TP is expected to give rise to the composite biomaterials with salient features potentially for various biomedical purposes.…”