Targeted Drug Action Research Articles

Anti-cancer potential of zerumbone in cancer and glioma: current trends and future perspectives.

Plant-derived immunomodulators and antitumor factors have appealed lots of attention from natural product scientists for their efficiency and safety and their important contribution to well-designed targeted drug action and delivery mechanisms. Zerumbone (ZER), the chief component of Zingiber zerumbet rhizomes, has been examined for its wide-spectrum in the treatment of multi-targeted diseases. The rhizomes have been used as food flavoring agents in numerous cuisines and in flora medication. Numerous in vivo and in vitro experiments have prepared confirmation of ZER as a potent immunomodulator as well as a potential anti-tumor agent. This review is an interesting compilation of all the important results of the research carried out to date to investigate the immunomodulatory and anticancer properties of ZER. The ultimate goal of this comprehensive review is to supply updated information and a crucial evaluation on ZER, including its chemistry and immunomodulating and antitumour properties, which may be of principal importance to supply a novel pathway for subsequent investigation to discover new agents to treat cancers and immune-related sickness. In addition, updated information on the toxicology of ZER has been summarized to support its safety profile.

Review on Virosomes: As a Drug Delivery Carriers

Since the last era, some revolutionary advances in drug delivery technologies have been observed in the realization of targeted drug delivery or targeted drug action at the site. The prospects for the use of biological molecules nanoparticles such as virosomes as drugs are motivating research and development areas that show the targeted fusion effects with the targeted fusion effects by target cells. Virosomes are biocompatible, biodegradable, non-toxic and non-autoimmunogeneous viral species and are new carriers and drug delivery systems for vaccines and cell delivery of active macromolecules. Virosomes are biomimetic nanoparticle drug delivery systems that contain active macromolecules in a virus coat made of lipoid membranes. The administration of virosomes takes place through various methods such as the intramuscular (IM), intravenous (IV), intravascular, subcutaneous (SC), oral and inhalation routes. The research paper focuses on the structure, components, types and formulations of virosomes, the mechanism of action and applications of viral genes, and available commercial formulations.

Rational Design in Photopharmacology with Molecular Photoswitches.

Photopharmacology is an attractive approach for achieving targeted drug action with the use of light. In photopharmacology, molecular photoswitches are introduced into the structure of biologically active small molecules to allow for the optical control of their potency. Going beyond trial and error, photopharmacology has progressively applied rational drug design methodologies to devise light-controlled bioactive ligands. In this review, we categorize photopharmacological efforts from the standpoint of medicinal chemistry strategies, focusing on diffusible photochromic ligands modified with photoswitches that operate through E-Z bond isomerization. In the vast majority of cases, photoswitchable ligands are designed as analogs of existing compounds, through a variety of approaches. By analyzing in detail a comprehensive list of instructive examples, we describe the state of the art and discuss future opportunities for rational design in photopharmacology.

Rational Design in Photopharmacology with Molecular Photoswitches

AbstractPhotopharmacology is an attractive approach for achieving targeted drug action with the use of light. In photopharmacology, molecular photoswitches are introduced into the structure of biologically active small molecules to allow for the optical control of their potency. Going beyond trial and error, photopharmacology has progressively applied rational drug design methodologies to devise light‐controlled bioactive ligands. In this review, we categorize photopharmacological efforts from the standpoint of medicinal chemistry strategies, focusing on diffusible photochromic ligands modified with photoswitches that operate through E‐Z bond isomerization. In the vast majority of cases, photoswitchable ligands are designed as analogs of existing compounds, through a variety of approaches. By analyzing in detail a comprehensive list of instructive examples, we describe the state of the art and discuss future opportunities for rational design in photopharmacology.

Solid Lipid Nanoparticles: Formulation, Preparation, and Characterization: A Review

The nano drug delivery system has emerged as a novel therapeutic approach for improved efficacy of the existing drug molecules. Polymeric nanoparticles, lipid based nanoparticles such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers, lipid drug conjugates, ethosomes, liposomes, and self-emulsifying drug delivery systems are a few of the nano carriers used for drug delivery. Among the lipid based nanoparticles, SLNs are promising in terms of a biocompatible carrier for enhancing the bioavailability, controlled release, and targeted drug action. This review explains the formulation components of SLN, various methods of preparation of SLNs, and the characterization parameters of SLNs. The current successful research on SLN formulation also enlightens. The capability of various drugs for increasing therapeutic efficacy can be achieved through SLN and in the future, new directions in further improvement are expected.

Immunomodulatory and antineoplastic efficacy of common spices and their connection with phenolic antioxidants

Background: Spices have generally offered a conventional way to avert and heal various communicable and non-communicable diseases due to their efficacy and safety and their noteworthy contribution towards understanding targeted drug action and drug delivery systems. Hence, the current investigation is designed to evaluate the immunomodulatory and antineoplastic efficacy of 15 spices that connect with the flavonoid and total polyphenol ingredients. This study includes the 15 adopted spices and their total flavonoid and polyphenol contents, cell viability assay (MTT), immunomodulatory efficacy (NO, TNF-α), and antineoplastic efficacy (using six cancer cell lines).Methods: The quantification of the flavonoid and phenolic content of methanolic extracts of 15 spices was performed by colorimetric assay. The immunomodulatory efficacy was studied according to their capacity to prevent NO and TNF-α synthesis in LPS stimulated RAW 264.7 macrophages. Cell viability was observed using MTT colorimetric assay. Antineoplastic efficacy was determined with six cancer cell lines, namely liver (HepG2), colon (HT29), breast (MCF7), pancreas (MIA PaCa2), lung (A549) and blood (Raji). Results: The outcome of significant immunomodulatory efficacy of the spices was noted in the following sequences: Acorus calamus L.(Inhibition of NO-49.32 ± 4.29 µg/mL and TNF-α 96.35 ± 8.23 µg/mL)> Alpinia galanga Wild (Inhibition of NO-55.69 ± 5.89µg/mL and TNF-α 102.36 ± 8.96 µg/mL)> Armoracia rusticana Gaerth (Inhibition of NO-82.44 ± 5.98 µg/mL and TNF-α 115.69 ± 7.59)> Capparis spinosa L. (Inhibition of NO-127.59 ± 5.68 µg/mL and TNF-α 123.58 ± 8.56 µg/mL) > Aframomum melegueta K. Schum (Inhibition of NO-169.89 ± 6.89 µg/mL and TNF-α 144.59 ± 7.89 µg/mL). The remaining spices considerably inhibited the generation of NO and TNF-α. All spices studied exhibited highly significant antineoplastic effects against all six cell lines. Noteworthy biological activities were observed in A. calamus, A. galanga, A. rusticana, C. spinose, and A. melegueta which have bulk quantities of polyphenols.Conclusion: Based on the present findings, spices are possible candidates for novel antioxidant, anti-inflammatory, and antineoplastic agents.Keywords: Spices; cancer cell lines; immunomodulatory; antineoplastic; total polyphenol contents

Molecular targeted therapy for advanced kidney cancer

Sorafenib is the first molecularly targeted drug for first-line treatment of patients with advanced kidney cancer and has achieved satisfactory results. Since then, a variety of molecularly targeted drugs have emerged, and the treatment of patients with advanced kidney cancer has entered a new era of molecular targeting. Molecular targeted therapy improves the clinical efficacy and response rate of patients, and prolongs the progression-free survival and overall survival of patients. Current targeted drugs include vascular endothelial growth factor inhibitors, mammalian target of rapamycin, immunological checkpoint inhibitors, etc. Understanding the mechanism of action and clinical efficacy of different targeted drugs, and analyzing the challenges of current targeted drugs from the perspective of gene mutation and drug resistance are helpful to the personalized treatment of patients with advanced renal cancer. Key words: Kidney neoplasms; Urologic neoplasms; Molecular targeted therapy; Antineoplastic agents; Precision medicine

A comprehensive review on Phyllanthus derived natural products as potential chemotherapeutic and immunomodulators for a wide range of human diseases

Abstract Treatment options for most cancers are still insufficient, despite developments and technology advancements. It has been postulated that the immune response to progressive tumors is insufficient due to a deficiency in afferent mechanisms responsible for the development of tumor-reactive T cells. Many patients treated for cancer will have their cancer recurrence, often after a long remission period. This suggests that there are a small number of tumor cells that remain alive after standard treatment(s) – alone or in combination and have been less effective in combating metastasis that represents the most elaborate hurdle to overcome in the cure of the disease. Therefore, any new effective and safe therapeutic agents will be highly demanded. To circumvent many plant extracts have attributed for their chemoprotective potentials and their influence on the human immune system. It is now well recognized that immunomodulation of immune response could provide an alternative or addition to conventional chemotherapy for a variety of disease conditions. However, many hurdles still exist. In recent years, there has been a tremendous interest either in harnessing the immune system or towards plant-derived immunomodulators as anticancer agents for their efficacy, safety and their targeted drug action and drug delivery mechanisms. This review discusses Phyllanthus Schum. & Thonn. their chemopreventive and immunomodulatory properties over the past few years. Although, as many as 500 important bioactive phytochemical compounds have been isolated from Phyllanthus their chemotherapeutic, immunomodulatory properties, molecular targets and modes of action are yet to be enlightened in detail. Hence, the theme of this review is very useful for further research on Phyllanthus species. because many phytochemicals from these plants have demonstrated preclinical therapeutic efficacy for a wide range of human diseases.

Cation tautomerism, twinning and disorder in the triclinic and monoclinic forms of 4-amino-5-chloro-2,6-dimethylpyrimidinium 5-chloro-2-hydroxybenzoate and a new disordered refinement of 2-amino-4,6-dimethoxypyrimidin-1-ium thiophene-2-carboxylate

Pyrimidines are important compounds in biology and medicine, and the aminopyrimidine fragment can be identified in three of the four bases in DNA. The targeted drug action of pharmaceuticals containing this functionality is likely to depend heavily on molecular recognition processes involving hydrogen bonding. Crystallization of an equimolar mixture of 4-amino-5-chloro-2,6-dimethylpyrimidine and 5-chloro-2-hydroxybenzoic acid yielded two forms of the 1:1 salt, C6H9ClN3+·C7H4ClO3-, each containing a different tautomeric form of the cation. 6-Amino-5-chloro-2,4-dimethylpyrimidin-1-ium 5-chloro-2-hydroxybenzoate, (I), crystallizes in the space group P-1, with Z' = 2, and all of the component ions are fully ordered. 4-Amino-5-chloro-2,6-dimethylpyrimidin-1-ium 5-chloro-2-hydroxybenzoate, (II), also crystallizes with Z' = 2, but in the space group P21/c and as a merohedral twin which closely mimics an orthorhombic unit cell. In (II), one of the cations and one of the anions is disordered, each over two sets of atomic sites having occupancies of 0.836 (2) and 0.164 (2), and 0.834 (2) and 0.166 (2). The bond lengths in the cations of (I) and (II) provide evidence for o-quinonoid and p-quinonoid bond fixation, respectively. A combination of six N-H...O hydrogen bonds links the component ions of (I) into two independent four-ion aggregates, but the ions in (II) are linked by a combination of four N-H...O and two N-H...N hydrogen bonds to form a three-dimensional framework structure. The recently reported structure of 2-amino-4,6-dimethoxypyrimidin-1-ium thiophene-2-carboxylate, C6H10N3O2+·C5H3O2S-, (III), has been rerefined, using the original data set, to show that the anion is disordered over two sets of atomic sites, approximately related by a 180° rotation about the exocyclic C-C bond, and having occupancies of 0.8687 (19) and 0.1313 (19).

Exploring the immunomodulatory and anticancer properties of zerumbone.

Plant-derived immunomodulators and anti-cancer agents have attracted a lot of interest from natural product scientists for their efficacy and safety and their significant contribution towards understanding targeted drug action and drug delivery mechanisms. Zerumbone, the main constituent of Zingiber zerumbet rhizomes, has been investigated for its wide-spectrum role in treating multitargeted diseases. The rhizomes have been used as food flavoring agents in various cuisines and in herbal medicine. Many in vivo and in vitro studies have provided evidence of zerumbone as a potent immunomodulator as well as a potential anti-cancer agent. This review is an interesting compilation of all those significant outcomes from investigations carried out to date to explore the immunomodulatory and anticancer properties of zerumbone. The ultimate objective of this comprehensive review is to provide updated information and a critical assessment on zerumbone including its chemistry and immunomodulating and anticancer properties, which may be of paramount importance to provide a new path for ensuing research to discover new agents to treat cancers and immune-related diseases. In addition, updated information on the toxicology of zerumbone has also been summarized to provide its safety profile.

Red-Shifting Azobenzene Photoswitches for in Vivo Use.

Recently, there has been a great deal of interest in using the photoisomerization of azobenzene compounds to control specific biological targets in vivo. These azo compounds can be used as research tools or, in principle, could act as optically controlled drugs. Such "photopharmaceuticals" offer the prospect of targeted drug action and an unprecedented degree of temporal control. A key feature of azo compounds designed to photoswitch in vivo is the wavelength of light required to cause the photoisomerization. To pass through tissue such as the human hand, wavelengths in the red, far-red, or ideally near infrared region are required. This Account describes our attempts to produce such azo compounds. Introducing electron-donating or push/pull substituents at the para positions delocalizes the azobenzene chromophore and leads to long wavelength absorption but usually also lowers the thermal barrier to interconversion of the isomers. Fast thermal relaxation means it is difficult to produce a large steady state fraction of the cis isomer. Thus, specifically activating or inhibiting a biological process with the cis isomer would require an impractically bright light source. We have found that introducing substituents at all four ortho positions leads to azo compounds with a number of unusual properties that are useful for in vivo photoswitching. When the para substituents are amide groups, these tetra-ortho substituted azo compounds show unusually slow thermal relaxation rates and enhanced separation of n-π* transitions of cis and trans isomers compared to analogues without ortho substituents. When para positions are substituted with amino groups, ortho methoxy groups greatly stabilize the azonium form of the compounds, in which the azo group is protonated. Azonium ions absorb strongly in the red region of the spectrum and can reach into the near-IR. These azonium ions can exhibit robust cis-trans isomerization in aqueous solutions at neutral pH. By varying the nature of ortho substituents, together with the number and nature of meta and para substituents, long wavelength switching, stability to photobleaching, stability to hydrolysis, and stability to reduction by thiols can all be crafted into a photoswitch. Some of these newly developed photoswitches can be used in whole blood and show promise for effective use in vivo. It is hoped they can be combined with appropriate bioactive targets to realize the potential of photopharmacology.

A review on proniosomal drug delivery system for targeted drug action.

Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of proniosomes in targeted drug action.

Diabetic Nephropathy: Causes and Managements

Uncontrolled diabetic patients often develop diabetic nephropathy (DN). Since, it involves different molecular pathways, such as polyol pathway, protein kinase-C (PKC) activation, inflammatory and oxidative stress etc., and so multi-targeted drugs would be required for its management. Although, combination therapies with various conventional medicines are already in use, but herbal preparations are being preferred as adjuvant therapy, because of their multi targeted drug action due to the presence of natural cocktail of various secondary metabolites. This review describes pathogenesis of DN, possible approaches for its management and information about recent patents and bio-products, which are in pipe line of drug development.

Diabetic Nephropathy: Causes and Managements

Uncontrolled diabetic patients often develop diabetic nephropathy (DN). Since, it involves different molecular pathways, such as polyol pathway, protein kinase - C (PKC) activation, inflammatory and oxidative stress etc., and so multi-targeted drugs would be required for its management. Although, combination therapies with various conventional medicines are already in use, but herbal preparations are being preferred as adjuvant therapy, because of their multi targeted drug action due to the presence of natural cocktail of various secondary metabolites. This review describes pathogenesis of DN, possible approaches for its management and information about recent patents and bio-products, which are in pipe line of drug development. Keywords: Chronic kidney disease, diabetic nephropathy, herbals, patented drugs, glomerular surface area, leucocytic infiltration, vascular remodeling, Hyperglycemic management, Hypertension management, Dietary Protein management

Formulation of Bioadhesive Carbomer Gel Incorporating Drug-Loaded Gelatin Microspheres for Periodontal Therapy

Purpose: To formulate carbomer gel to localize and target drug action in periodontal pockets. Methods: Diclofenac sodium (DS, anti-inflammatory) and metronidazole hydrochloride (MH, antibacterial) were loaded in gelatin microspheres using glutaraldehyde cross-linking. The microspheres were evaluated for drug loading, entrapment and encapsulation efficiency, particle size, drug release as well as by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The microspheres were incorporated into carbomer gel and evaluated for drug release. Results: Loading, entrapment and encapsulation efficiencies of DS in the microsphere were 23.4, 93.6, and 74.9 w/w%, respectively, while for MH the values were 21.5, 86.0 and 73.1 % w/w, respectively. Mean particle size of unloaded microspheres, DS- and MH-loaded microspheres was 33.5, 67.8 and 51.4 µm, respectively. SEM showed spherical geometry of microspheres while DSC indicated the amorphous nature of t entrapped DS and MH. Sustained release of DS and MH over a 4-h period from the microspheres and gel was achieved. Conclusion: Carbomer gel loaded with microspheres of diclofenac and metronidazole is a potential localized delivery system for the treatment inflammation and infection in periodontal pockets.

Abstract 3777: Applying mechanistic pharmacokinetic-pharmacodynamic models (PKPD) to describe the growth and inhibition of xenograft tumors in rats and mice by targeted anticancer agents

Abstract Introduction: M. Simeoni et al., Cancer Res 64, 1094-1101 (2004) published a mathematical model, which is now widely used in pre-clinical experimentation to describe the growth and inhibition by anti-cancer agents of mouse and rat xenograft models. It models drug-concentration induced cell damage, and uses a series of transit-compartments to introduce delay into the system and empirically describe populations of cells undergoing subsequent stages of cell damage and death. The model involves a number of simplifying assumptions: All healthy cells are equally susceptible to drug treatment at all times; drug action is linearly related to drug concentration; drug action causes cell damage and death with a single rate of progress through a series of empirical transit compartments; DNA damage repair mechanisms are assumed not to exist. B. Ribba et al. Eur. J. Cancer, 47, 479-490 (2011) recently demonstrated the utility of a mechanistic model that characterizes the tumor xenograft in terms of non-hypoxic, hypoxic, and necrotic cells and the drug action on these sub-populations of cells. In this poster we will illustrate several modeling approaches that have been utilized when the simplifying assumptions in the Simeoni model are invalid. We will also extend the model presented by Ribba et al., to incorporate the spatial features of a tumor in an attempt to better describe the tumor micro-environment. Methods: We have adapted the Simeoni and Ribba models to be more mechanistic by incorporating features that describe: (1) the utility of biomarkers proximal to the target in cell signaling pathways as a driver for growth inhibition; (2) multiple mechanisms of drug action on sub-populations of cells that drive tumor growth. Pharmacokinetic, biomarker and tumor growth data for example compounds have been used to demonstrate the utility of these mechanistic models. Results: Incorporating non-linearity between drug exposure, biomarker response, and tumor growth inhibition allows observed differences between dosing schedules to be explained. Replacing drug exposure with a biomarker as the driver for tumor growth inhibition provides a more meaningful surrogate for pharmacological action, particularly in the situation where biomarker response to drug is significantly delayed compared to the pharmacokinetics. Modeling multiple mechanisms of action on sub-populations of cells can allow an accurate representation of the drug effect on the disease biology. Conclusions: We demonstrate that adding mechanistic features to a descriptive model of drug-induced tumor growth inhibition makes it more representative of the disease biology and drug action. This offers the opportunity for modeling targeted drug action, which was not possible with the original model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3777. doi:1538-7445.AM2012-3777

Functionalized bridged silsesquioxane-based nanostructured microspheres: ultrasound-assisted synthesis and in vitro cytotoxicity characterization

Different kinds of polymers have been employed in medicine as biomaterials for different purposes. In recent years, considerable attention has been focused on the development of new drug-delivery systems in order to increase bio-availability, sustain, localize and target drug action in the human body. The versatility of the sol-gel processing to synthesize nanostructured materials and the possibility of incorporating organic molecules into the matrix of the final hybrid material, represent a novel and attractive path to the synthesis of new functionalized hybrid biomaterials with advanced properties. In this work, acetylsalicylic acid (ASA)-functionalized hybrid microspheres based on bridged silsesquioxanes synthesized via ultrasound-assisted sol-gel processing, were characterized. An investigation concerning the cytotoxic response of these new microspheres on CHO-K1 cells was accomplished based on ISO 10993-5 standard (Biological Evaluation of Medical Devices). Microspheres incorporating ASA showed a cytotoxic effect when pure extracts of the microspheres were analyzed, however, they strongly diminished their cytotoxicity as the extracts were diluted. When a 10% concentration extract was employed, hybrid microspheres were shown to be non cytotoxic. These results are promising for considering these novel functionalized organic-inorganic microspheres as potential drug-carriers to be employed in drug delivery-related applications.

N-Aryl-substituted 3-(β-D-glucopyranosyloxy)-2-methyl-4(1H)-pyridinones as agents for Alzheimer's therapy

Molecules designed to sequester, redistribute and/or remove metal ions are attractive therapeutic agents in neurodegenerative diseases such as Alzheimer's disease. The multifactorial nature of the condition and the generally poor target specificity associated with metal ion-binding therapy has led to the development of multifunctional 3-hydroxy-4-(1H)-pyridinone pro-ligands. The excellent qualities of the basic 3-hydroxy-4-pyridinone framework as a low toxicity metal chelator and an antioxidant, as well as its antibacterial and analgesic properties among other functions, inspired us to functionalize it with a framework derived from thioflavin-T, the well-known traditional dye used as a marker to detect amyloid deposits in tissue sections. Thus 2-methyl-3-hydroxy-1-(4-dimethylaminophenyl)-4(1H)-pyridinone (HL1), 2-methyl-3-hydroxy-1-(4-methylaminophenyl)-4(1H)-pyridinone (HL2), 1-(4-aminophenyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (HL3), 1-(6-benzothiazolyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (HL4), 1-(2-benzothiazolyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (HL5) and 2-methyl-3-hydroxy-1-[4-(4-bromophenyl)-2-thiazolyl]-4(1H)-pyridinone (HL6) were obtained. Glycosylation, as well as incorporation of structures mimicking those of known amyloid imaging agents, may target drug action to the site of interest, the metal-overloaded amyloid plaques in the Alzheimer's brain. The pro-ligands were assessed for their antioxidant activity, cytotoxicity and ability to interfere with metal ion-induced amyloid peptide aggregation to screen promising lead compounds. Finally, in a brain uptake study with a radiolabeled glucoconjugate pyridinone, 3-(β-D-glucopyranosyloxy)-1-[4-(4-[125I]iodophenyl)-2-thiazolyl]-2-methyl-4(1H)-pyridinone ([125I]-GL7) was shown to cross the blood–brain barrier using an in situ rat brain perfusion technique.

Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

Illuminating cellular physiology: recent developments.

Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified.