Guoting Qin

Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery

A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 °C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

Synthesis and evaluation of a near-infrared fluorescent non-peptidic bivalent integrin αvβ3 antagonist for cancer imaging

Computer modeling approaches to identify new inhibitors are essentially a very sophisticated and efficient way to design drugs. In this study, a bivalent nonpeptide intergrin alpha(v)beta(3) antagonist (bivalent IA) has been synthesized on the basis of an in silico rational design approach. A near-infrared (NIR) fluorescent imaging probe has been developed from this bivalent compound. In vitro binding assays have shown that the bivalent IA (IC(50) = 0.40 +/- 0.11 nM) exhibited improved integrin alpha(v)beta(3) affinity in comparison with the monovalent IA (IC(50) = 22.33 +/- 4.51 nM), resulting in an over 50-fold improvement in receptor affinity. NIR imaging probe, bivalent-IA-Cy5.5 conjugate, also demonstrated significantly increased binding affinity (IC(50) = 0.13 +/- 0.02 nM). Fluorescence microscopy studies showed integrin-mediated endocytosis of bivalent-IA-Cy5.5 in U87 cells which was effectively blocked by nonfluorescent bivalent IA. We also demonstrated tumor accumulation of this NIR imaging probe in U87 mouse xenografts.

Synthesis and evaluation of bivalent, peptidomimetic antagonists of the αvβ3 integrins

Targeting the integrin α(v)β(3) by directly interfering with its function is considered to be an effective and non-cytotoxic strategy for the treatment of tumor. In this study, a series of bivalent analogs of peptidomimetic integrin antagonists IA 1 and IAC 2 were designed, synthesized, and evaluated for their ability to inhibit the integrin α(v)β(3). All the bivalent ligands exhibited increased potency compared to that of their monomeric counterparts for the integrin α(v)β(3) with low nanomolar range binding affinity. The best bivalent ligand 6 tested in the series has an IC(50)=0.09 nM evaluated by ELISA assay. We conclude that multivalency is providing a useful template for the development novel integrin α(v)β(3) antagonists as potential therapeutics.

Preparation, characterization, and protein-resistance of films derived from a series of α-oligo(ethylene glycol)-ω-alkenes on H–Si(111) surfaces

A series of oligo(ethylene glycol) (OEG)-terminated monolayers were prepared by photo-activated grafting of OEG-alkenes with the general formula CH2CH(CH2)m(OCH2CH2)nOCH3 (abbreviated as Cm+2EGn, m = 8, 9; n = 3–7) on hydrogen-terminated silicon (111) surfaces using different deposition conditions. The films were characterized by contact-angle goniometry, ellipsometry, X-ray photoelectron spectroscopy (XPS) and tested for protein resistance. Films prepared under a higher vacuum showed a higher thickness and exhibited better protein resistance with increasing ethylene glycol (EG) units. Remarkably, the films prepared from C10EGn were generally thicker than those from their corresponding homologues C11EGn, and displayed better resistance to protein adsorption, which were probably due to the odd–even effect from the alkyl chain. Prepared under high vacuum conditions (∼10−5 mbar), the C10EG7 films with a thickness of 40 A adsorbed <0.8% (the detection limit of N 1s XPS) monolayer of fibrinogen in a standard assay. The films remained protein-resistant (adsorbed <3% monolayer of fibrinogen) even after 28 days in phosphate buffered saline (PBS) at 37 °C or 17 days in MC3T3-E1 cell culture with 10% fetal bovine serum at 37 °C. Therefore, the C10EG7 films prepared under high vacuum conditions represent the most protein-resistant and stable films on non-oxidized silicon substrates.