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• Organometallic metal complexes have been utilized for biosensing and imaging. • There are also good examples of anticancer d6, d8 and d10 metal complexes. • Luminescent and anticancer metal complexes have been employed as theranostic agents. • Self-assembled metal complexes have good potentials for biomedical applications. • Chemical biology can facilitate biological studies of metal complexes. Organometallic d6, d8 and d10 metal complexes are known for their interesting photophysical and photochemical properties. This allows many of them to develop into luminescent probes for biosensing and imaging. In addition, some of the complexes have been found to show promising anticancer properties, with different molecular targets from the classical cisplatin and platinum-based chemotherapeutic agents, illustrating the possibility of using them to develop new therapy for cancers. Notably, there are examples of luminescent metal complexes showing good therapeutic values. They have been employed as theranostic agents which enable diagnosis and therapy simultaneously. This review highlights key features of organometallic d6, d8 and d10 metal complexes reported in the past 10 years and their applications in biosensing, imaging, cancer treatment and theranosis. We also discuss the limitations found in these complexes and provide insights into the future development of organometallic metal complexes for biomedical applications. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Metal-Organic Frameworks (MOFs) as platform in of advanced combined therapy. • Biocompatibility is achieved by selecting non-toxic and/or endogenous building units. • Large porosity enables the co-encapsulation of multiple drugs in MOFs. • MOFs scaffolds can be used for theranosis, combining therapy and imaging. Abstract Different strategies have been developed to overcome limitations of traditional pharmacological treatments (biodegradation, low specificity, toxicity, side effects). Remarkably, the use of nanoplatforms as Drug Delivery Systems (DDS) to control the dose and the delivery kinetics of active ingredients (AIs) stands out as promising new generation of personalized therapies. Among other proposed materials, Metal-Organic Frameworks (MOFs) offer multiple versatilities for the accommodation of AIs: adaptable structure based on organic ligands and inorganic clusters as building units (BUs), that can be AIs themselves; accessible porosity and large surface areas; availability of functionalization sites; and biodegradability, among others. It is of great importance that MOFs, selected as bioplatforms, are biocompatible and do not exhibit toxicity. Even there are plenty of studies and reviews that explored the use of MOFs as DDS, they often include a single AI. In contrast, we wanted to focus on this review on MOF bioplatforms that exhibit advanced combined therapies. These advanced therapies could be achieved by: i) the co-encapsulation and simultaneous or sequential release of two or more AIs (e.g. drugs, metals, gases, biomolecules), ii) effective drug delivery at a target site after external triggered stimulus (near infrared-NIR, magnetic field), iii) monitoring administration towards a specific target (bioimaging), iv) combined AIs delivery and diagnosis (theranosis), and v) detection of different analytes (biosensors). All the promising combined advanced therapies based on MOFs bioplatforms herein reported open the path for the development of more efficient treatments. [ABSTRACT FROM AUTHOR]

Nanotechnology plays an important role in the development of drug delivery, imaging, and diagnosis. In this study, nanocapsules containing protein-functionalized gold nanoclusters (AuNCs) as the shell and hydrophobic drug curcumin as the core were prepared as a tumor cell theranostic agent. After the nanocapsules were added into tumor cell media, they entered the cells with high efficiency and exhibited strong fluorescence within the cells. The results indicated that the nanocapsules were broken up in the cells and curcumin was released. Simultaneously, the nanocapsules exhibited significant inhibition effect against tumor cell proliferation in a concentration- and time-dependent manner, and the images of atomic force microscopy (AFM) showed that the cell morphology underwent obvious changes after the capsule treatment. Additionally, cell membrane appeared wrinkles after the cells treated with the nanocapsules, resulting in a rough cell surface, implying that the cytoskeleton would involve in the cell uptake of nanocapsules. Moreover, the AuNCs and curcumin in the system could exert synergistic effect on the inhibition of tumor cell growth and induction of cell apoptosis. The study highlights the potential of the system as a promising agent for drug delivery and tumor cell theranosis. [ABSTRACT FROM AUTHOR]

Bloodstream bacterial infections are a serious threat to global public health and economy. The recent figures released by National Center for Health Statistics indicate that more than a million Americans get affected by it each year and the sepsis mortality alone is about 28%-50% Hall et al. (2011). 1 Robust and affordable point-of-care medical technologies are, therefore, urgently needed for rapid decision-making to initiate appropriate line of treatment. Current techniques based on blood culture and serology do not have quick turnaround times or adequate sensitivities for early intervention. Moreover, antimicrobial resistance poses a great challenge in the fight towards effective bacterial infection management. Nanotheranostics is emerging as a novel strategy combining solutions for rapid diagnosis and treatment in a more personalized way. This review highlights the recent advances made in theranosis of bloodstream bacterial infections using different classes of nanomaterials and bioreceptors, and discusses present challenges and future way forward. [ABSTRACT FROM AUTHOR]

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T 1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. [ABSTRACT FROM AUTHOR]

Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro- and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd(III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500 nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro . The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37 °C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles. In summary, chitosan drug-loaded nanobubbles with Gd(III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anti-cancer treatments. [ABSTRACT FROM AUTHOR]

Abstract: Targeting tissues/cells using probing materials to detect diseases such as cancer and inflammatory disease has been attempted with some success. Most of the molecular targets used in diagnosis and therapy were identified through the discovery of intracellular signaling pathways. Among intracellular signaling processes, the ubiquitination of proteins, and thereby their proteasomal degradation, is important because it plays a role in most diseases involving alterations to a component of the ubiquitination system, particularly E3 ligases, which have selective target-binding affinity and are key to the success of regulating the disorder. The regulation and monitoring of E3 ligases can be achieved using peptides containing protein–protein binding motifs. We generated a human protein-derived peptide that could target Smurf1, a member of the E3 ligase family, by competitively binding to osteo-Smads. To effectively deliver it into cells, the peptide was further modified with a cell-penetrating peptide. The peptide contains two fluorescent dyes: fluorescein isothiocyanate (FITC; absorbance/emission wavelengths: 495/519 nm) as a fluorophore and black hole quencher-1 (BHQ-1) as a fluorescence quencher. When the target Smurf1 combined with complementary sequences in the peptide probe, the distance between the fluorophore and BHQ-1 increased via a conformational change, resulting in the recovery of the fluorescence signal. Simultaneously, the degradation of Smad1/5/8 was blocked by the binding of the peptide probe to Smurf1, leading to the potentiation of the osteogenic pathway, which was reflected by an increase in the expression of osteoinductive genes, such as alkaline phosphatase and osteocalcin. Possible future applications of the peptide probe include its integration into imaging tools for the diagnosis of Smurf1-overexpressing diseases. [Copyright &y& Elsevier]

The work aimed at developing a MRI-guided protocol for the visualization of the release of material entrapped in liposomes stimulated by the local application of pulsed low-intensity non-focused ultrasound (pLINFU). The task was achieved by formulating liposomes filled up with the clinically approved paramagnetic agent gadoteridol, because the release of the agent from the nanovesicles is accompanied by a significant MRI signal enhancement. The protocol was validated in vivo on mice-bearing subcutaneous syngeneic B16 melanoma and i.v. injected with the paramagnetic liposomes. Upon exposing tumor to pLINFU (3MHz, insonation time 2min, duty cycle 50%) few minutes after liposomes injection, a signal enhancement of ca. 35% was detected. The effective release of the agent was confirmed by the strong enhancement measured in kidneys calyx and bladder due to the rapid renal excretion of the agent released in the tumor. [ABSTRACT FROM AUTHOR]

Abstract: A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T 2 -weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r 2 relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were – 70.4 ± 4.3% versus – 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy. [Copyright &y& Elsevier]

Theranostic nanomedicine was successfully prepared using layered double hydroxide (LDH). By means of step-by-step incorporation of an anticancer drug, methotrexate (MTX), and a radioisotope, Co-57, into the interlayer space and lattice of LDH, respectively, theranostic hybrid Nanomedicine could be prepared. X-ray diffractometry, scanning electron microscopy, X-ray adsorption spectroscopy, and Fourier-transform infrared spectroscopy systematically showed that incorporating the Co2+ into the MTX-LDH did not alter the crystalline phase, size, morphology, or intact structure of the hybrid. The labeled Co-57 in MTX-LDH was highly stable in human serum, showing almost 90% retention after 48 h. In vitro cellular uptake of Co-57-labeled MTX-LDH was very high in mouse colon carcinoma CT-26 cells, with ~60 ID% at 4 h. The cytotoxicity assay of MTX-LDH showed high cancer-cell suppression on CT-26 cells. To evaluate the diagnostic ability of Co-57-labeled MTX-LDH, in vivo single-photon emission computed tomography (SPECT) images were investigated on CT-26 xenografted mouse model. The SPECT signal in tumor tissue began to appear within 1 h, and it increased for 3 h. Unlabelled Image • Theranostic nanomedicine based on LDH was successfully prepared. • The radioisotope was substituted and drug was intercalated into LDH. • The radioisotope tracer, Co-57, showed rapid contrasting effect in tumor model. • The loaded drug showed high anticancer activity through efficient delivery. [ABSTRACT FROM AUTHOR]