Imaging‐Guided pHe and Glutathione Dual Responsive Polypeptide Nanogel for Smart Drug Delivery

A negatively charged polypeptide nanogel, near‐infrared (NIR) cyanine dye (Cy5.5) conjugated and 2,3‐dimethylmaleic anhydride (DMA) modified poly‐l ‐lysine‐co‐l ‐cystine (CDPLC), is synthesized and is used as an imaging‐guided sequential drug delivery system. The CDPLC nanogel can respond to two general stimulations in sequence: extracellular tumor acidic microenvironment pHe (6.8–6.5) and intracellular high concentration glutathione (GSH). Under pHe, the DMA shell of the nanogel is removed and a charge reversal takes place, resulting in positively charged nanogel which can be internalized by cancer cells easily. Once internalized into tumor cells, the increased intracellular GSH concentration further promotes DOX release from the nanogel and DOX is enriched to the nucleus. Cy5.5 is conjugated to the nanogel as an NIR fluorescent probe, making it possible for imaging‐guided drug delivery, which is confirmed by the MTT and confocal laser scanning microscopy via in vitro experiments. The as‐prepared nanogel is a potential theranostic for cancer therapy.     

Bioorthogonally Applicable Fluorescence Deactivation Strategy for Receptor Kinetics Study and Theranostic Pretargeting Approaches

The availability of a receptor for theranostic pretargeting approaches was assessed by use of a new click‐chemistry‐based deactivatable fluorescence‐quenching concept. The efficacy was evaluated in a cell‐based model system featuring both membranous (available) and internalized (unavailable) receptor fractions of the clinically relevant receptor chemokine receptor 4 (CXCR4). Proof of concept was achieved with a deactivatable tracer consisting of a CXCR4‐specific peptide functionalized with a Cy5 dye bearing a chemoselective azide handle (N₃‐Cy5‐AcTZ14011). Treatment with a Cy7 quencher dye (Cy7‐DBCO) resulted in optically silent Cy7‐[click]‐Cy5‐AcTZ14011. In situ, a >90 % FRET‐based reduction of the signal intensity of N₃‐Cy5‐AcTZ14011 [K_D=(222.4±25.2) nm ] was seen within minutes after quencher addition. In cells, discrimination between the membranous and the internalized receptor fraction could be achieved through quantitative assessment of quenching/internalization kinetics. Similar evaluation of an activatable tracer variant based on the same targeting moiety (Cy5‐S‐S‐Cy3‐AcTZ14011) was unsuccessful in vitro. As such, using the described deactivatable approach to screen membrane receptors and their applicability in receptor‐(pre‐)targeted theranostics can become straightforward.     

Design and Synthesis of Imidazo[2,1‐b]thiazole–Chalcone Conjugates: Microtubule‐Destabilizing Agents

A series of chalcone conjugates featuring the imidazo[2,1‐b]thiazole scaffold was designed, synthesized, and evaluated for their cytotoxic activity against five human cancer cell lines (MCF‐7, A549, HeLa, DU‐145 and HT‐29). These new hybrid molecules have shown promising cytotoxic activity with IC₅₀ values ranging from 0.64 to 30.9 μM . Among them, (E)‐3‐(6‐(4‐fluorophenyl)‐2,3‐bis(4‐methoxyphenyl)imidazo[2,1‐b]thiazol‐5‐yl)‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one ( 11 x ) showed potent antiproliferative activity with IC₅₀ values ranging from 0.64 to 1.44 μM in all tested cell lines. To investigate the mechanism of action, the detailed biological aspects of this promising conjugate ( 11 x ) were carried out on the A549 lung cancer cell line. The tubulin polymerization assay and immunofluoresence analysis results suggest that this conjugate effectively inhibits microtubule assembly in A549 cells. Flow cytometric analysis revealed that this conjugate induces cell‐cycle arrest in the G2/M phase and leads to apoptotic cell death. This was further confirmed by Hoechst staining, activation of caspase‐3, DNA fragmentation analysis, and Annexin V–FITC assay. Moreover, molecular docking studies indicated that this conjugate ( 11 x) interacts and binds efficiently with the tubulin protein.     

Hexaphyrin as a Potential Theranostic Dye for Photothermal Therapy and 19F Magnetic Resonance Imaging

Two features of meso‐Aryl‐substituted expanded porphyrins suggest suitability as theranostic agents. They have excellent absorption in near infrared (NIR) region, and they offer the possibility of introduction of multiple fluorine atoms at structurally equivalent positions. Here, hexaphyrin (hexa) was synthesized from 2,6‐bis(trifluoromethyl)‐4‐formyl benzoate and pyrrole and evaluated as a novel expanded porphyrin with the above features. Under NIR illumination hexa showed intense photothermal and weak photodynamic effects, which were most likely due to its low excited states, close to singlet oxygen. The sustained photothermal effect caused ablation of cancer cells more effectively than the photodynamic effect of indocyanine green (a clinical dye). In addition, hexa showed potential for use in the visualization of tumors by ¹⁹F magnetic resonance imaging (MRI), because of the multiple fluorine atoms. Our results strongly support the utility of expanded porphyrins as theranostic agents in both photothermal therapy and ¹⁹F MRI.     

Magnetospirillum magneticum as a Living Iron Chelator Induces TfR1 Upregulation and Decreases Cell Viability in Cancer Cells

Interest has grown in harnessing biological agents for cancer treatment as dynamic vectors with enhanced tumor targeting. While bacterial traits such as proliferation in tumors, modulation of an immune response, and local secretion of toxins have been well studied, less is known about bacteria as competitors for nutrients. Here, we investigated the use of a bacterial strain as a living iron chelator, competing for this nutrient vital to tumor growth and progression. We established an in vitro co-culture system consisting of the magnetotactic strain Magnetospirillum magneticum AMB-1 incubated under hypoxic conditions with human melanoma cells. Siderophore production by 10⁸ AMB-1/mL in human transferrin (Tf)-supplemented media was quantified and found to be equivalent to a concentration of 3.78 µM ± 0.117 µM deferoxamine (DFO), a potent drug used in iron chelation therapy. Our experiments revealed an increased expression of transferrin receptor 1 (TfR1) and a significant decrease of cancer cell viability, indicating the bacteria’s ability to alter iron homeostasis in human melanoma cells. Our results show the potential of a bacterial strain acting as a self-replicating iron-chelating agent, which could serve as an additional mechanism reinforcing current bacterial cancer therapies.     

Cell-Penetrating Peptide-Conjugated BF2-Oxasmaragdyrins as NIRF Imaging and Photothermal Agents

Cell-penetrating peptides (CPPs) are excellent cell internalizing agents for hydrophobic drug/dye moieties. We exploited this property of CPPs for the cell internalization of BF₂-oxasmaragdyrin by constructing covalent conjugates of BF₂-oxasmaragdyrin with CPPs (CRGDK and polyarginine (R₉)) using a solid-phase peptide synthesis (SPPS) methodology. The CPP-conjugated BF₂-oxasmaragdyrins were purified by reversed-phase HPLC and characterized by mass spectrometry. The CPP-conjugated BF₂-oxasmaragdyrins were found to be photostable, absorb in the visible-NIR region (400–700 nm), emit in the NIR−I region (∼715–720 nm) with moderate quantum yields, and be biocompatible, with excellent cellular imaging potential in breast cancer cells (MDA-MB-231). The R₉ conjugate, being the first water-soluble BF₂-oxasmaragdyrin, also possesses excellent photothermal transduction efficacy with 750 nm laser irradiation and is a potential theranostic agent.     

Tyrosinase‐mediated in situ forming hydrogels from biodegradable chondroitin sulfate–tyramine conjugates

Tyrosinase‐mediated crosslinking of chondroitin sulfate–tyramine (CS‐TA) conjugates was successfully applied in the preparation of biodegradable in situ forming hydrogels under physiological conditions. Depending on the polymer concentration, the degree of substitution of TA residue and the tyrosinase concentration, the gelation times ranged from 2.3 to 129 min. Studies on the gel contents of CS‐TA hydrogels showed that their degrees of crosslinking could be controlled by varying the tyrosinase concentrations. CS‐TA hydrogels could be completely degraded by the chondroitinase ABC within a time range from 6 days to 11 weeks. CS‐TA hydrogels possessed highly elastic properties and their storage moduli varied from 120 to 1300 Pa, as determined by rheological analysis. Scanning electron microscopy observation confirmed that CS‐TA hydrogels contained a well‐interconnected pore structure. A live–dead assay demonstrated that NIH 3T3 fibroblasts incorporated in CS‐TA hydrogels retained their viability. In addition, in vitro release of methylene blue (a photodynamic therapy drug) from CS‐TA hydrogels could be effectively sustained by the drug encapsulation in the hydrogels. This study indicates that tyrosinase‐mediated in situ forming CS‐TA hydrogels are promising for biomedical applications including drug release and tissue engineering. © 2012 Society of Chemical Industry     

Molecular‐Target‐Based Anticancer Photosensitizer: Synthesis and in vitro Photodynamic Activity of Erlotinib–Zinc(II) Phthalocyanine Conjugates

Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib–zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR‐overexpressing cancer cells owing to the presence of the small molecular‐target‐based anticancer agent erlotinib. All conjugates were found to be essentially non‐cytotoxic in the absence of light (up to 50 μM ), but upon illumination, they show significantly high photo‐cytotoxicity toward HepG2 cells, with IC₅₀ values as low as 9.61–91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm^?2). Structure–activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular‐target‐based photodynamic therapy.     

Fabrication of galactosylated chitosan–5‐fluorouracil acetic acid based nanoparticles for controlled drug delivery

In this study, a novel type of macromolecular prodrug, N‐galactosylated chitosan (GC)?5‐fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC–FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC–FUA. The structure of the as‐prepared GC–FUA was characterized by Fourier transform infrared and ¹H‐NMR analyses. The average particle size of the GC–FUA nanoparticles was 160.1 nm, and their drug‐loading content was 21.22 ± 2.7% (n = 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC–FUA nanoparticles. An in vitro drug‐release study showed that the GC–FUA nanoparticles displayed a sustained‐release profile compared to 5‐fluorouracil‐loaded GC nanoparticles. All of the results suggest that the GC–FUA nanoparticles may have great potential for anti‐liver‐cancer applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42625.     

Chitosan–Quercetin Bioconjugate as Multi‐Functional Component of Antioxidants and Dual‐Responsive Hydrogel Networks

Multifunctional hydrogels based on chitosan–quercetin (CHITQ) conjugate are prepared by a thermo‐induced radical procedure in the presence of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and N,N′‐methylenebis(acrylamide) (MEBA). At first, quercetin (Q) is grafted onto chitosan backbone with a functionalization degree of 275 mg of Q per gram of conjugate, as calculated by ¹H‐NMR analyses to impart antioxidant properties to the polysaccharide. Then, a pH and temperature sensitive hydrogel was obtained by involving CHITQ and NIPAAm in the polymerization reaction. The accessibility of phenolic moieties is modified in response to the hydrogel swelling/deswelling, as confirmed by antioxidant tests performed at different temperatures. Dual stimuli‐responsive hydrogels are proposed for the delivery of caffeine as model drug. The release profiles of caffeine depict a system particularly performing as on/off device at acidic pH with excellent applicability prospects.     

Design,Synthesis, and Evaluation of an 18F‐Labeled Radiotracer Based on Celecoxib–NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase‐2 (COX‐2)

A series of novel fluorine‐containing cyclooxygenase‐2 (COX‐2) inhibitors was designed and synthesized based on the previously reported fluorescent COX‐2 imaging agent celecoxib–NBD ( 3 ; NBD=7‐nitrobenzofurazan). In vitro COX‐1/COX‐2 inhibitory data show that N‐(4‐fluorobenzyl)‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide ( 5 ; IC₅₀=0.36 μM , SI>277) and N‐fluoromethyl‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide ( 6 ; IC₅₀=0.24 μM , SI>416) are potent and selective COX‐2 inhibitors. Compound 5 was selected for radiolabeling with the short‐lived positron emitter fluorine‐18 (¹⁸F) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [¹⁸F] 5 was analyzed in vitro and in vivo using human colorectal cancer model HCA‐7. Although radiotracer uptake into COX‐2‐expressing HCA‐7 cells was high, no evidence for COX‐2‐specific binding was found. Radiotracer uptake into HCA‐7 tumors in vivo was low and similar to that of muscle, used as reference tissue.     

Near‐infrared‐active and pH‐responsive fluorescent polymer‐integrated hybrid graphene oxide nanoparticles for the detection and treatment of cancer

Hybrid nanoparticles for theragnosis have great potentiality to bring desire functionalities in one integrated system. The development of bioimaging guided photothermal therapy (PTT) is pivotal in optimizing cytotoxic cancer therapy. We report near‐infrared (NIR)‐active and pH‐responsive fluorescent, catechol‐conjugated, reduced graphene oxide (rGO)‐anchored hybrid nanoparticles that can sharply increase the photothermal heat in response to NIR exposure and exhibit pH‐dependent fluorescence emission for the detection of tumor areas without causing cell toxicity. The optoelectronic absorption property of poly(3,4‐ethylenedioxythiophene) [PEDOT]:dopamine‐conjugated poly(4‐styrenesulfonate‐co‐maleic acid) [D‐PSM] and 3′,4′‐dihydroxyacetophenone/boron‐dipyrromethene [CCDP/BODIPY]‐quaternized polyethylene glycol grafted poly(dimethylaminoethyl methacrylate) (C/B‐PgP) present in this hybrid nanoparticles resulted in efficient photothermal conversion with pH‐tunable fluorescence that exerted sufficient photothermal cytotoxicity to cancer cells. The in vitro cellular uptake was measured by confocal laser scanning microscopy, allowing the therapeutic efficiency and bioimaging effects to be explored. We expect that the broad optical absorption property of PEDOT:D‐PSM with BODIPY‐conjugated polymers on rGO sheets would get tremendous attraction in this enormous rising PTT with cancer detectable biomarker. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43791.     

Synthesis and characterization of new poly(ethylene glycol)bisphosphonate vinylic monomer and non-fluorescent and NIR-fluorescent bisphosphonate micrometer-sized particles

Bisphosphonates (BPs) are non-hydrolysable pyrophosphate analogs with high affinity to hydroxyapatite (HAP, the main inorganic ingredient in bones) and are mainly used for bone diseases treatments.A new stable PEG-BP monomer and particles have been prepared for enhanced long term bone-targeted imaging and therapy applications. The new formed BP particles possess dual functionalities: chelation to the bone mineral, HAP, through the BP groups and covalent attachment of a dye or drug through primary amine groups.The BP particles showed no cytotoxic effect on human osteosarcoma cell lines and minor toxicity on mouse macrophage cells, indicating that these BP particles are good candidates for in vivo testing. The BP monomer and particles exhibited inhibition of HAP formation and dissolution, similar to a commercial Alendronate. Near IR (NIR) fluorescent BP particles were obtained by conjugation of Cy7-NHS ester to the primary amine groups of the BP particles.     

Human Serum Transferrin Fibrils: Nanomineralisation in Bacteria and Destruction of Red Blood Cells

Fibrils formed by human serum transferrin [(1–3 μM ) apo‐Tf, partially iron‐saturated (Fe_0.6‐Tf) and holo‐Tf (Fe₂‐Tf) forms], from dilute bicarbonate solutions, were deposited on formvar surfaces and studied by electron microscopy. We observed that possible bacterial contamination appears to give rise to long, pea‐pod‐like (PPL) structures for Fe₂‐Tf, attributable to the formation of polyhydroxybutyrate (PHB) storage granules, under the nutrient‐limiting conditions used. These PPL structures contained periodic nanomineralisation sites susceptible to uranyl stain. Extended incubation of transferrin solutions (about four days) gave rise to extensive transferrin fibril structures. Optical microscopy and AFM studies showed that red blood cells (RBCs) readily adhere to these fibrils. Moreover, the fibrils appear to penetrate RBC membranes and to induce rapid cell destruction (within about 5 h). It is speculated that in situations in vivo where transferrin fibrils can form, such interactions might have adverse physiological consequences, and further studies could aid the understanding of related pathological events.     

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

The present study describes the synthesis and anticancer activity of novel octahedral Pt^IV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these Pt^IV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt^IV complexes against various cancer cell lines (IC₅₀ range: 1.9–8.7 μM ) was higher than that of cisplatin (IC₅₀ range: 10.9–67.0 μM ) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt^IV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.     

Synthesis and Biological Evaluation of N‐Substituted Noscapine Analogues

Noscapine is a phthalideisoquinoline alkaloid isolated from the opium poppy Papaver somniferum. It has long been used as an antitussive agent, but has more recently been found to possess microtubule‐modulating properties and anticancer activity. Herein we report the synthesis and pharmacological evaluation of a series of 6′‐substituted noscapine derivatives. To underpin this structure–activity study, an efficient synthesis of N‐nornoscapine and its subsequent reduction to the cyclic ether derivative of N‐nornoscapine was developed. Reaction of the latter with a range of alkyl halides, acid chlorides, isocyanates, thioisocyanates, and chloroformate reagents resulted in the formation of the corresponding N‐alkyl, N‐acyl, N‐carbamoyl, N‐thiocarbamoyl, and N‐carbamate derivatives, respectively. The ability of these compounds to inhibit cell proliferation was assessed in cell‐cycle cytotoxicity assays using prostate cancer (PC3), breast cancer (MCF‐7), and colon cancer (Caco‐2) cell lines. Compounds that showed activity in the cell‐cycle assay were further evaluated in cell viability assays using PC3 and MCF‐7 cells.     

Synthesis of tercopolymer BA–MMA–VTES and surface modification of nano‐size Si3N4 with this macromolecular coupling agent

A new macromolecular coupling agent butyl acrylate (BA)‐methyl methacrylate (MMA)‐vinyl triethoxy silane (VTES) tercopolymer was synthesized using solution polymerization initiated by free radical initiator benzoyl peroxide (BPO) and dicumyl peroxide (DCP). Dodecylthiol is choosed as the chain transfer to control the molecule weight of this tercopolymer. The terpolymer's molecular structure was confirmed by FTIR and NMR, and its average molecular weight was determined by GPC. In this work, the tercopolymer BA–MMA–VTES is used for surface modification of silicon nitride (Si₃N₄) nanopowder. The structure surface properties and thermal stability of modified nano‐Si₃N₄ were systematically investigated by FTIR, TGA, TEM, and size distribution analyzer. The results show that the macromolecular coupling agent bonds covalently on the surface of nano‐sized Si₃N₄ particles and an organic coating layer is formed. The optimum loading of this macromolecular coupling agent BA–MMA–VTES tercopolymer is 5% (wt %) of nano‐sized Si₃N₄. TEM also reveals that modified nano‐Si₃N₄ possesses good dispersibility. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Synthesis and tunable thermoresponsive solution morphologies of 2,2‐bis‐methylolpropionic acid dendron–azobenzene–poly(N‐isopropyl acrylamide) copolymers

Amphiphilic temperature‐ and photoresponsive linear–dendritic block copolymers comprising second‐generation acetonide‐2,2‐bis‐methylolpropionic acid‐based polyester dendron and linear poly(N‐isopropyl acrylamide) (PNIPAM) linked by an azobenzene unit were synthesized using atom transfer radical polymerization (ATRP) followed by click chemistry. Linear PNIPAM precursor was prepared from an azide‐functionalized azobenzene containing ATRP initiator. Two polymers obtained by varying the chain length of the PNIPAM block showed different morphologies and lower critical solution temperature (LCST) values in aqueous solution. Complete change in morphology of the two polymers into large spherical aggregates and nanotubes, respectively, was observed upon heating the micellar solution above LCST. The azobenzene unit was found to undergo trans–cis photoisomerization in the assemblies and caused a change in the microenvironment of an encapsulated hydrophobic dye without any release. Acetonide groups on the dendron were deprotected to afford hydroxylated polymer that showed well‐defined morphologies above the LCST and after heating–cooling cycle while significant dye encapsulation was seen only above the LCST. © 2017 Society of Chemical Industry     

Effect of pH,ionic strength,and temperature on uranyl ion adsorption by poly(N‐vinyl 2‐pyrrolidone‐g‐tartaric acid) hydrogels

Poly‐electrolyte N‐vinyl 2‐pyrrolidone‐g‐tartaric acid (PVP‐g‐TA) hydrogels with varying compositions were prepared in the form of rods from ternary mixtures of N‐vinyl 2‐pyrrolidone/tartaric acid/water. The effect of external stimuli, such as the solution pH, ionic strength, and temperature, on uranyl adsorption by these hydrogels was investigated. Uranyl adsorption capacities of the hydrogels were determined to be 53.2–72.2 (mg UO/g dry gel) at pH 1.8, and 35.3–60.7 (mg UO/g dry gel) at pH 3.8, depending on the amount of TA in the hydrogel. The adsorption studies have shown that the temperature and the ionic strength of the swelling solution also influence uranyl ion adsorption by PVP‐g‐TA hydrogels. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 2219–2226, 2000     

Fluorophore‐Labeled Cyclooxygenase‐2 Inhibitors for the Imaging of Cyclooxygenase‐2 Overexpression in Cancer: Synthesis and Biological Studies

A group of cyclooxygenase‐2 (COX‐2)‐specific fluorescent cancer biomarkers were synthesized by linking the anti‐inflammatory drugs ibuprofen, (S)‐naproxen, and celecoxib to the 7‐nitrobenzofurazan (NBD) fluorophore. In vitro COX‐1/COX‐2 inhibition studies indicated that all of these fluorescent conjugates are COX‐2 inhibitors (IC₅₀ range: 0.19–23.0 μM ) with an appreciable COX‐2 selectivity index (SI≥4.3–444). In this study the celecoxib–NBD conjugate N‐(2‐((7‐nitrobenzo[c][1,2,5]oxadiazol‐4‐yl)amino)ethyl)‐4‐(5‐(p‐tolyl)‐3‐(trifluoromethyl)‐1H‐pyrazol‐1‐yl)benzenesulfonamide ( 14 ), which displayed the highest COX‐2 inhibitory potency and selectivity (COX‐2 IC₅₀=0.19 μM ; SI=443.6), was identified as an impending COX‐2‐specific biomarker for the fluorescence imaging of cancer using a COX‐2‐expressing human colon cancer cell line (HCA‐7).