Targeting peptide functionalized liposomes towards aminopeptidase N for precise tumor diagnosis and therapy.

Aminopeptidase N (APN/CD13) is closely related to the growth of cancers and is suggested as a suitable target for anti-cancer therapy. Based on the "one-bead-one-compound" (OBOC) approach on a microarray device, we screened out a novel affinity peptide LN (YEVGHRC). It was determined that LN could specifically recognize and bind to APN. Moreover, LN-functionalized liposomes (LN-LS) could achieve efficient nano-encapsulated drug delivery under APN-overexpressing tumor conditions in vitro and in vivo. We expect that LN-LS could provide a new strategy for APN-positive tumor diagnosis and therapy.

Switchable Liposomes: Targeting-Peptide-Functionalized and pH-Triggered Cytoplasmic Delivery.

One switchable nanodelivery system was constructed. Liposomes were functionalized by a novel dual-recognition peptide STP, which is pH-responsive as well as the affinity ligand of tumor marker VEGFR2 (the angiogenesis marker vascular endothelial growth factor receptor 2). Efficient drug delivery and in vivo therapy could be "turned on" and accelerated only in the conditions of VEGFR2 overexpression and a mild acidic environment. We envisioned that the successful demonstration of this switchable nanocarrier system would open a new avenue on rapid cytoplasmic delivery for specific cancer diagnostics and therapeutics.

Micromixer Based Preparation of Functionalized Liposomes and Targeting Drug Delivery.

We present here a specific targeting nanocarrier system by functionalization of liposomes with one new type of breast cancer targeting peptide (H6, YLFFVFER) by a micromixer with high efficiency. Antitumor drugs could be successfully delivered into human epidermal growth factor receptor 2 (HER2) positive breast cancer cells with high efficiency in both in vivo and ex vivo models.

Peptide functionalized targeting liposomes: for nanoscale drug delivery towards angiogenesis.

A novel affinity peptide S1 (LIDHEWKENYFPLSF) was screened out via a "one bead one compound" (OBOC) approach on a microarray device. It was identified that S1 could specifically recognize and bind to vascular endothelial growth factor receptor 2 (VEGFR2), which is an angiogenesis biomarker. Moreover, S1-functionalized liposomes (S1-LS) could achieve efficient nanoscale drug delivery under the conditions of VEGFR2-overexpression in vitro and in vivo. It was demonstrated that S1-LS would be a promising VEGFR2-targeting drug delivery system.

Inhibition of catechol-o-methyltransferase (COMT) by myricetin, dihydromyricetin, and myricitrin.

Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson's disease through boosting the concentration of dopamine in the brain. Development of COMT inhibitors can efficiently increase the bioavailability of L-dopa. The present study aims to evaluate the inhibition of COMT activity by three herbal components isolated from Myrica rubra Sieb. et Zucc.. The in vitro human liver cytosol-catalyzed L-dopa methylation reaction was utilized. The results showed that all these three compounds strongly inhibited COMT activity in a concentration-dependent manner. The inhibition was competitive for these three compounds, as demonstrated by Dixon and Lineweaver-Burk plots. The inhibition kinetic parameters (Ki) towards COMT activity were calculated to be 0.5, 0.2, and 0.9 microM for myricitrin, myricetin, and dihydromyricetin, respectively. From the view of structures, the deglycosylation biotransformation of myricitrin into myricetin can increase the inhibitory ability towards COMT. However, further structural alteration of myricetin towards dihydromyricetin weakens the inhibitory potential towards COMT.

Preparation of biocompatible carboxymethyl chitosan nanoparticles for delivery of antibiotic drug.

OBJECTIVE: To prepare biocompatible ciprofloxacin-loaded carboxymethyl chitosan nanoparticles (CCC NPs) and evaluate their cell specificity as well as antibacterial activity against Escherichia coli in vitro. METHODS: CCC NPs were prepared by ionic cross-linking method and optimized by using Box-Behnken response surface method (BBRSM). Zeta potential, drug encapsulation, and release of the obtained nanoparticles in vitro were thoroughly investigated. Minimum inhibitory concentration (MIC) and killing profiles of free or ciprofloxacin-loaded nanoparticles against Escherichia coli were documented. The cytotocity of blank nanoparticles and cellular uptake of CCC NPs were also investigated. RESULTS: The obtained particles were monodisperse nanospheres with an average hydrated diameter of 151 ± 5.67 nm and surface of charge -22.9 ± 2.21 mV. The MICs of free ciprofloxacin and CCC NPs were 0.16 and 0.08 µg/mL, respectively. Blank nanoparticles showed no obvious cell inhibition within 24 h, and noticeable phagocytosis effect was observed in the presence of CCC NPs. CONCLUSION: This study shows that CCC NPs have stronger antibacterial activity against Escherichia coli than the free ciprofloxacin because they can easily be uptaken by cells. The obtained CCC NPs have promising prospect in drug delivery field.