Following nanomedicine activation with magnetic resonance imaging:Why, how, and what's next?

Nanomedicines, such as liposomal formulations, play an important role in cancer therapy. To support their development, medical imaging modalities are employed for following the drug delivery. Encapsulation of MRI contrast agents, which change their relaxivity upon co-release with the drug, is a promising strategy for monitoring both the biodistribution and payload release from a nanocarrier. This approach is successfully applied in preclinical settings to image the activation of liposomes responsive to heat, pH changes or sonication. Recent advances include combination with different treatments and the implementation of chemical exchange saturation transfer imaging to gain spectral resolution over different contrast agents. However, this field still faces challenges, such as matching the pharmacokinetic profiles of the contrast agents and the liberated drugs

A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging

Optical imaging of microbial infections, based on the detection of targeted fluorescent probes, offers high sensitivity and resolution with a relatively simple and portable setup. As the absorbance of near-infrared (NIR) light by human tissues is minimal, using respective tracers, such as IRdye800CW, enables imaging deeper target sites in the body. Herein, we present a general strategy for the conjugation of IRdye800CW and IRdye700DX to small molecules (vancomycin and amphotericin B) to provide conjugates targeted toward bacterial and fungal infections for optical imaging and photodynamic therapy. In particular, we present how the use of coupling agents (such as HBTU or HATU) leads to high yields (over 50%) in the reactions of amines and IRDye-NHS esters and how precipitation can be used as a convenient purification strategy to remove excess of the targeting molecule after the reaction. The high selectivity of the synthesized model compound Vanco-800CW has been proven in vitro, and the development of analogous agents opens up new possibilities for diagnostic and theranostic purposes. In times of increasing microbial resistance, this research gives us access to a platform of new fluorescent tracers for the imaging of infections, enabling early diagnosis and respective treatment

A Photocleavable Contrast Agent for Light-Responsive MRI

Thanks to its innocuousness and high spatiotemporal resolution, light is used in several established and emerging applications in biomedicine. Among them is the modulation of magnetic resonance imaging (MRI) contrast agents' relaxivity with the aim to increase the sensitivity, selectivity and amount of functional information obtained from this outstanding whole-body medical imaging technique. This approach requires the development of molecular contrast agents that show high relaxivity and strongly pronounced photo-responsiveness. To this end, we report here the design and synthesis of a light-activated MRI contrast agent, together with its evaluation using UV-vis spectroscopy, Fast Field Cycling (FFC) relaxometry and relaxometric measurements on clinical MRI scanners. The high relaxivity of the reported agent changes substantially upon irradiation with light, showing a 17% decrease in relaxivity at 0.23T upon irradiation with lambda = 400 nm (violet) light for 60 min. On clinical MRI scanners (1.5T and 3.0T), irradiation leads to a decrease in relaxivity of 9% and 19% after 3 and 60 min, respectively. The molecular design presents an important blueprint for the development of light-activatable MRI contrast agents

Beyond Photodynamic Therapy:Light-Activated Cancer Chemotherapy

Background: Cancer chemotherapy is limited by severe side effects due to unspecific cytotoxic activity of currently used therapeutics. In order to minimize these unwanted effects, several approaches have been taken, relying on the use of light to activate drugs. As light can be delivered with a very high spatiotemporal resolution, this technique is a promising strategy to selectively activate cytotoxic drugs at their site of action and thus to improve the tolerability and safety of chemotherapy. Objective: This review summarizes different approaches towards photoactivated chemotherapy and identifies its challenges and opportunities. Results: The respective papers were summarized and evaluated in terms of their phototherapeutic indices and the wavelength needed for activation. First, the design, synthesis and/or evaluation of photoactivated metal complexes including platinum-, ruthenium-, and rhodium-complexes is described. Next, photocaged metal complexes and photoacaged organic chemotherapeutics are reported, with a wide range of cytotoxicity mechanisms. The final part includes, examples of photoswitchable drugs for cancer therapy. Some designs, especially metal complexes, stand out due to their very high phototherapeutic index (> 1880) but the common drawback of light-responsive metal complexes and organic chemotherapeutics is the irreversibility of activation. Photoswitchable drugs, however, address this challenge. Nevertheless, the need of UV light for their activation still limits their application. Conclusion: The field of photoactivated cancer chemotherapy is rapidly growing and already includes very promising approaches with designs providing high phototherapeutic indices and also NIR or visible light-activatable drugs

A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging

Optical imaging of microbial infections, based on the detection of targeted fluorescent probes, offers high sensitivity and resolution with a relatively simple and portable setup. As the absorbance of near-infrared (NIR) light by human tissues is minimal, using respective tracers, such as IRdye800CW, enables imaging deeper target sites in the body. Herein, we present a general strategy for the conjugation of IRdye800CW and IRdye700DX to small molecules (vancomycin and amphotericin B) to provide conjugates targeted toward bacterial and fungal infections for optical imaging and photodynamic therapy. In particular, we present how the use of coupling agents (such as HBTU or HATU) leads to high yields (over 50%) in the reactions of amines and IRDye-NHS esters and how precipitation can be used as a convenient purification strategy to remove excess of the targeting molecule after the reaction. The high selectivity of the synthesized model compound Vanco-800CW has been proven in vitro, and the development of analogous agents opens up new possibilities for diagnostic and theranostic purposes. In times of increasing microbial resistance, this research gives us access to a platform of new fluorescent tracers for the imaging of infections, enabling early diagnosis and respective treatment