Hand-Ground Nanoscale ZnII -Based Coordination Polymers Derived from NSAIDs: Cell Migration Inhibition of Human Breast Cancer Cells.

Increased levels of intracellular prostaglandin E2 (PGE2 ) have been linked with the unregulated cancer cell migration that often leads to metastasis. Non-steroidal anti-inflammatory drugs (NSAIDs) are known inhibitors of cyclooxygenase (COX) enzymes, which are responsible for the increased PGE2 concentration in inflamed as well as cancer cells. Here, we demonstrate that NSAID-derived ZnII -based coordination polymers are able to inhibit cell migration of human breast cancer cells. Various NSAIDs were anchored to a series of 1D ZnII coordination polymers through carboxylate-Zn coordination, and these structures were fully characterized by single-crystal X-ray diffraction. Hand grinding in a pestle and mortar resulted in the first reported example of nanoscale coordination polymers that were suitable for biological studies. Two such hand-ground nanoscale coordination polymers NCP1 a and NCP2 a, which contained naproxen (a well-studied NSAID), were successfully internalized by the human breast cancer cells MDA-MB-231, as was evident from cellular imaging by using a fluorescence microscope. They were able to kill the cancer cells (MTT assay) more efficiently than the corresponding mother drug naproxen, and most importantly, they significantly inhibited cancer cell migration thereby displaying anticancer activity.

Exploiting supramolecular synthons in designing gelators derived from multiple drugs.

A simple strategy for designing salt-based supramolecular gelators comprised of various nonsteroidal anti-inflammatory drugs (NSAIDs) and amantadine (AMN) (an antiviral drug) has been demonstrated using a supramolecular synthon approach. Single-crystal and powder X-ray diffraction established the existence of the well-studied gel-forming 1D supramolecular synthon, namely, primary ammonium monocarboxylate (PAM) synthon in all the salts. Remarkably five out of six salts were found to be capable of gelling methyl salicylate (MS)-an important ingredient in commercially available topical gels; one such selected biocompatible salt displayed an anti-inflammatory response in prostaglandin E2 (PGE2 ) assay, thereby indicating their plausible biomedical applications.

Hydrogen-bonding-induced chain folding and vesicular assembly of an amphiphilic polyurethane.

We have reported synthesis and vesicular assembly of a novel amphiphilic polyurethane with hydrophobic backbone and hydrophilic pendant carboxylic acid groups which were periodically grafted to the backbone via a tertiary amine group. In aqueous medium the polymer chain adopted a folded conformation which was stabilized by intrachain H-bonding among the urethane groups. Such a model was supported by concentration and solvent-dependent FT-IR, powder XRD, and urea-mediated "denaturation" experiments. Folded polymer chains further formed vesicular assembly which was probed by dynamic light scattering, TEM, AFM, SEM, and fluorescence microscopic studies, and dye encapsulation experiments. pH-dependent DLS and fluorescence microscopic studies revealed stable polymersome in entire tested pH window of 3.5-11.0. Zeta potential measurements showed a negatively charged surface in basic pH while a charge-neutral surface in neutral and acidic pH. MTT assay with CHO cell line indicated good cell viability.

ß-Amino acid and amino-alcohol conjugation of a nonsteroidal anti-inflammatory drug (NSAID) imparts hydrogelation displaying remarkable biostability, biocompatibility, and anti-inflammatory properties.

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with ß-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable (1)H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure-property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns).