Development and In Vitro Evaluation of Linear PEI-Shelled Heparin/Berberine Nanoparticles in Human Osteosarcoma U-2 OS Cells

Abstract

Berberine (BBR), a natural isoquinoline alkaloid derived from Chinese herbs, exerts many biological effects, including antiviral, antimicrobial, antidiarrhea, anti-inflammatory, and antitumor effects. In this study, a novel berberine nanoparticle (NP) consisting of heparin (HP) and BBR with or without being shelled with linear polyethyleneimine (LPEI) was developed to enhance its antitumor activity on osteosarcoma U-2 OS cells. With varying ratios of HP to BBR, HP/BBR NPs had a size ranging from 218.4 ± 3.9 to 282.0 ± 5.1 nm and zeta potential from −35.7 ± 0.4 to −51.9 ± 1.8 mV. After shelling with LPEI, the resultant NPs (HP/BBR/LPEI) possessed a size ranging from 226.3 ± 3.0 to 405.7 ± 85.2 nm and zeta potential from −46.5 ± 0.3 to −35.6 ± 0.5 mV; the encapsulation rate of BBR was close to 80%. The release profiles of both NPs were revealed to be slower than that of BBR solution. Results also showed that BBR and its two derived NPs reduced the viability of U-2 OS cells, and BBR NPs increased the cellular uptake of BBR. Cells were arrested at the G1 phase when treated individually with BBR and the two NPs (HP/BBR and HP/BBR/LPEI) and DNA condensation was induced. In addition, BBR and BBR NPs reduced the expression of mouse double minute 2 homolog (MDM2) but increased that of p53, and BBR NPs enhanced apoptotic effects. In short, heparin-based nanoparticles could be potential carriers for osteosarcoma treatment.

Dual concentration-dependent effect of ascorbic acid on PAP(248–286) amyloid formation and SEVI-mediated HIV infection

“…Ascorbic acid (AA) has been shown to have potential therapeutic effects against several neurodegenerative diseases such as AD, PD, Huntington's disease (HD) and ischemic stroke. 54,64,72,73 Furthermore, AA has been shown to interact with Aβ, stefin B, and insulin resulting in inhibition of their aggregation. 30,60 Human semen, which naturally contains SEVI amyloid, also contains a number of vitamins amongst which AA is in the highest concentration (0.4±0.1 mM).…”

“…[60][61][62][63][64] In addition to interaction with the β-sheet backbone of amyloids, AA has been shown to exert inhibition of amyloid fibril formation through its degradation products, such as ascorbate anions and dehydroascorbic acid. 72,73 The stability of AA varies with pH and incubation temperature, where self-degradation products are obtained within ~6 hours under physiological pH at 37 ˚C. 60,72 These degradation products were found to inhibit fibrillation and disrupt preformed mature amyloid fibrils of insulin, with an activity positively correlated with the degree of AA degradation.…”

“…72,73 The stability of AA varies with pH and incubation temperature, where self-degradation products are obtained within ~6 hours under physiological pH at 37 ˚C. 60,72 These degradation products were found to inhibit fibrillation and disrupt preformed mature amyloid fibrils of insulin, with an activity positively correlated with the degree of AA degradation. 72,73 The metabolites of AA were shown to shield the electrostatic interactions between the β-sheet forming areas of protein monomers prone to form amyloid structures and to disrupt β-sheet stacking.…”

“…60,72 These degradation products were found to inhibit fibrillation and disrupt preformed mature amyloid fibrils of insulin, with an activity positively correlated with the degree of AA degradation. 72,73 The metabolites of AA were shown to shield the electrostatic interactions between the β-sheet forming areas of protein monomers prone to form amyloid structures and to disrupt β-sheet stacking. 60 Since in our in vitro assay, effects on fibril formation were seen after 24 hours, we speculate that such degradation products might contribute to the amyloid inhibitory effects observed at concentrations of AA higher than its physiological concentration.…”

Recent updates in COVID-19 with emphasis on inhalation therapeutics: Nanostructured and targeting systems

“…NPs can be used as smart systems for antiviral activity by coating, enclosing, overlay the drugs and imaging agents [ 102 , 103 ]. Hsu et al [ 104 ], prepared a novel berberine NP containing heparin and berberine coated with linear polyethyleneimine (LPEI) for antiviral activity. Berberine (BBR) is a famous Chinese herbal isoquinoline alkaloid with multiple biological consequences: antivirals, antimicrobials, antidiarrheal, and antitumor activities.…”