pH-Activated Targeting Drug Delivery System Based on the Selective Binding of Phenylboronic Acid

Abstract

Phenylboronic acid (PBA) is a tumor-targeting molecule, but its nonspecific interaction with normal cells or other components containing cis-diol residues undoubtedly limits its potential application in tumor-targeting drug delivery. Herein, we developed fructose-coated mixed micelles via PBA-terminated polyethylene glycol monostearate (PBA-PEG-C18) and Pluronic P123 (PEG20-PPG70-PEG20) to solve this problem, as the stability of borate formed by PBA and fructose was dramatically dependent on pH. The fluorescence spectroscopic results indicated that the borate formed by PBA and fructose decomposed at a decreased pH, and better binding between PBA and sialic acid (SA) was observed at a low pH. These results implied that the fructose groups decorated on the surface of the micelles could be out-competed by SA at a low pH. In vitro uptake and cytotoxicity studies demonstrated that the fructose coating on the mixed micelles improved the endocytosis and enhanced the cytotoxicity of drug-loaded mixed micelles in HepG2 cells but reduced the cytotoxicity in normal cells. These results demonstrate that a simple decorating strategy may facilitate PBA-targeted nanoparticles for tumor-specific drug delivery.

Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

“…Therefore, this innovative utilization of the CCI as a unique binding force for SA recognition, reversible transition of material macroscopic properties and satisfactory enrichment application give a glimpse of the significance of this distinctive biomolecule interaction, which might will spark people’s interests on CCI in various bio-related applications. For example, due to over-expressed SA-containing glycans in tumor cells surface and acidic intratumor microenvironment, this specific SA recognition capacity of our polymer material may provide a new methods to develop tumor-targeting drug delivery system21. Moreover, it is also conceivable that this smart polymer shows potential for early diagnosis and monitor of cancers by reversibly capture and release circulating tumor cells22.…”

“…Thus, for related researches of SAs detection or sialylation profiling, it is of great importance to recognize and capture the target SA molecules, such as various free SAs, sialylated glycans, peptides or proteins1920. Currently, commonly used approaches for SAs recognition were mainly based on phenylboronic acid derivatives or phenylboronic acid-functionalized polymer2122, exhibiting to people a potential tool for both diagnostic and therapeutic applications related to cancers23. However, for some SAs derivatives, particularly sialylated glycopeptides (SGs) that were found frequently in various cancer cells and widely known as cancer biomarkers, it is still a thorny issue for researchers to achieve the specific recognition, capture, and even selective separation, due to the ultra-low abundance of the SA derivatives (lower than 0.03% in total amount of protein hydrolysates) and strong interference from other saccharides or peptides2425.…”

Design and Construction of a Smart Targeting Drug Delivery System Based on Phototriggered Competition of Host–Guest Interaction

“…The critical aggregation concentration (CAC) of Ad‐lys(F 68 )‐PS and biotin‐F 68 ‐biotin was determined by surface tension method according to the previous report, respectively. First, an optical contact angle measuring device (OCA 30, Datephysics) was utilized to determine the surface tension values of the sample solutions with concentration gradients.…”

Dual-sensitive chitosan derivative micelles for site-specific drug release in the treatment of chicken coccidiosis

“…18 Collectively, the hydrophobic segments graed onto chitosan would improve the amphiphilic properties of the polymers, which may form self-assembled micelles in water and enable encapsulation of the hydrophobic drugs. 19,20 Besides, chitosan and its derivatives could enhance the adhesion to the intestinal mucosa and open the intestinal epithelial cells tight junctions (TJs) to promote intestinal absorption. 21,22 As a food additive for animal feed, chitosan was well known for some benets such as immunomodulatory, antimicrobial and hypocholesterolemic features to improve the growth rate of broiler chickens.…”