Roles of free radicals in type 1 phototherapeutic agents: aromatic amines, sulfenamides, and sulfenates.

Detailed analyses of the electron spin resonance (ESR) spectra, cell viability, and DNA degradation studies are presented for the photolyzed Type I phototherapeutic agents: aromatic amines, sulfenamides, and sulfenates. The ESR studies provided evidence that copious free radicals can be generated from these N-H, N-S, and S-O containing compounds upon photoirradiation with UV/visible light. The analyses of spectral data allowed us to identify the free radical species.

Non-destructive and selective imaging of the functionally active, pro-invasive membrane type-1 matrix metalloproteinase (MT1-MMP) enzyme in cancer cells.

Proteolytic activity of cell surface-associated MT1-matrix metalloproteinase (MMP) (MMP-14) is directly related to cell migration, invasion, and metastasis. MT1-MMP is regulated as a proteinase by activation and conversion of the latent proenzyme into the active enzyme, and also via inhibition by tissue inhibitors of MMPs (TIMPs) and self-proteolysis. MT1-MMP is also regulated as a membrane protein through its internalization and recycling.

In vitro efficacy of paclitaxel-loaded dual-responsive shell cross-linked polymer nanoparticles having orthogonally degradable disulfide cross-linked corona and polyester core domains.

Paclitaxel-loaded shell cross-linked polymeric nanoparticles having an enzymatically and hydrolytically degradable poly(lactic acid) core and a glutathione-responsive disulfide cross-linked poly(oligoethylene glycol)-containing corona were constructed in aqueous solution and investigated for their stimuli-responsive release of the embedded therapeutics and in vitro cytotoxicity. Paclitaxel release from the nanoparticles in PBS buffer was accelerated in the presence of glutathione at both pH 5.5 and pH 7.

Poly(ethylene oxide)--polyphosphester-based Paclitaxel Conjugates as a Platform for Ultra-high Paclitaxel-loaded Multifunctional Nanoparticles.

A new type of degradable, nanoscopic polymer assembly containing ultra-high levels of drug loading covalent attachment within amphiphilic core-shell nanoparticle morphology has been generated as a potentially effective and safe anti-cancer agent. Poly(ethylene oxide)--polyphosphoester-based paclitaxel drug conjugates (PEO--PPE--PTX) were synthesized by rapid, scalable and versatile approach that involves only two steps: organocatalyst-promoted ring-opening-polymerization followed by click reaction-based conjugation of a PTX prodrug. Variations in the polymer-to-PTX stoichiometries allowed for optimization of the conjugation efficiency, the PTX drug loading and the resulting water solubilities of the entire polymer and the PTX content.

Paclitaxel-loaded SCK nanoparticles: an investigation of loading capacity and cell killing abilities in vitro.

Block copolymer nanoparticles having two different hydrodynamic diameters (120 nm vs 50 nm) and core diameters (60 nm vs 20 nm) with variable paclitaxel loading (5 to 20 wt % with respect to polymer weight, 4.4 μg/mL to 21.7 μg/mL paclitaxel concentrations in ultrapure water) were prepared for their in vitro cytotoxicity evaluation.

Antibody targeting of cell-bound MUC1 SEA domain kills tumor cells.

The cell-surface glycoprotein MUC1 is a particularly appealing target for antibody targeting, being selectively overexpressed in many types of cancers and a high proportion of cancer stem-like cells. However the occurrence of MUC1 cleavage, which leads to the release of the extracellular α subunit into the circulation where it can sequester many anti-MUC1 antibodies, renders the target problematic to some degree. To address this issue, we generated a set of unique MUC1 monoclonal antibodies that target a region termed the SEA domain that remains tethered to the cell surface after MUC1 cleavage.

Type 1 Phototherapeutic Agents. 2. Cancer Cell Viability and ESR Studies of Tricyclic Diarylamines.

Type 1 phototherapeutic agents based on diarylamines were assessed for free radical generation and evaluated in vitro for cell death efficacy in the U937 leukemia cancer cell line. All of the compounds were found to produce copious free radicals upon photoexcitation with UV-A and/or UV-B light, as determined by electron spin resonance (ESR) spectroscopy. Among the diarylamines, the most potent compounds were acridan (4) and 9-phenylacridan (5), with IC50 values of 0.

Type 1 phototherapeutic agents, part I: preparation and cancer cell viability studies of novel photolabile sulfenamides.

Novel type 1 phototherapeutic agents based on compounds containing S-N bonds (sulfenamides) were synthesized, assessed for free radical generation, and evaluated in vitro for cell death efficacy in four cancer cell lines (U937, HTC11, KB, and HT29). All of the compounds were found to produce copious free radicals upon photoexcitation with UV-A and/or UV-B light, as determined by electron spin resonance spectroscopy. Among the sulfenamides, the most potent compounds were derived from dibenzazepine 7b and dihydroacridine 8b as determined in all of the four cancer cell lines.

Tunable dual-emitting shell-crosslinked nano-objects as single-component ratiometric pH-sensing materials.

Dual-emitting photonic nano-objects that can sense changes in the environmental pH are designed based on shell-crosslinked micelles assembled from amphiphilic block copolymers and crosslinked with pH-insensitive chromophores. The chromophoric crosslinkers are tetra-functionalized pyrazine molecules that bear a set of terminal aliphatic amine groups and a set of anilino amine groups, which demonstrate morphology-dependent reactivities towards the poly(acrylic acid) shell domain of the nano-objects. The extent to which the anilino amine groups react with the nano-object shell is shown to affect the hypsochromic shift (blue-shift).