Fluorescence imaging techniques have been widely used to visualize biological molecules and phenomena. In particular, several studies on the development of small-molecule fluorescent probes have been carried out, because their fluorescence properties can be easily tuned by synthetic chemical modification. For this reason, various fluorescent probes have been developed for targeting biological components, such as proteins, peptides, amino acids, and ions, to the interior and exterior of cells. In this review, we cover advances in the development of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based fluorescent probes for biological studies over the past decade.

BODIPY-based probes for the fluorescence imaging of biomolecules in living cells

Pharmacotherapy is often severely hindered by issues related to poor drug selectivity, including side effects, environmental toxicity, and the emergence of resistance. Lack of selectivity is caused by the inability to control drug activity in time and space. Photopharmacology aims at solving this issue by incorporating photoswitchable groups into the molecular structure of bioactive compounds. These switching units allow for the use of light as an external control element for pharmacological activity, which can be delivered with very high spatiotemporal precision. This Perspective presents the reader with the current state and outlook on photopharmacology. In particular, the principles behind photoregulation of bioactivity, the challenges of molecular design, and the possible therapeutic scenarios are discussed.

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Photopharmacology: Beyond Proof of Principle

Photocleavable protecting groups (PPGs) are extensively used in chemical and biological sciences. In their application, advantage is taken of using light as an external, non-invasive stimulus, which can be delivered with very high spatiotemporal precision. More recently, orthogonally addressing multiple PPGs, in a single system and with different wavelengths of light, has been explored. This approach allows one to independently control multiple functionalities in an external, non-invasive fashion. In this tutorial review, we discuss the design principles for dynamic systems involving wavelength-selective deprotection, focusing on the choice and optimization of PPGs, synthetic methods for their introduction and strategies for combining multiple PPGs into one system. Finally, we illustrate the design principles with representative examples, aiming at providing the reader with an instructive overview on how the wavelength-selective cleavage of photoprotecting groups can be applied in materials science, organic synthesis and biological systems.

Wavelength-selective cleavage of photoprotecting groups: strategies and applications in dynamic systems

Photoresponsive nanoparticles for drug delivery

Periodic Mesoporous Organosilica (PMO) nanomaterials are envisioned to be one of the most prolific subjects of research in the next decade. Similar to mesoporous silica nanoparticles (MSN), PMO nanoparticles (NPs) prepared from organo-bridged alkoxysilanes have tunable mesopores that could be utilized for many applications such as gas and molecule adsorption, catalysis, drug and gene delivery, electronics, and sensing; but unlike MSN, the diversity in chemical nature of the pore walls of such nanomaterials is theoretically unlimited. Thus, we expect that PMO NPs will attract considerable interest over the next decade. In this review, we will present a comprehensive overview of the synthetic strategies for the preparation of nanoscaled PMO materials, and then describe their applications in catalysis and nanomedicine. The remarkable assets of the PMO structure are also detailed, and insights are provided for the preparation of more complex PMO nanoplatforms.

Syntheses and applications of periodic mesoporous organosilica nanoparticles

Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two-photon excitation has significant advantages deep in biological tissues, but raises problems in the design of "smart" probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two-photon probes.

From one-photon to two-photon probes: "caged" compounds, actuators, and photoswitches.

Molekulare Systeme, die mit Licht “ferngesteuert” werden konnen, sind von wachsender Bedeutung in der Zellbiologie, der Physiologie und den Neurowissenschaften. Der entscheidende Aspekt hierbei ist die hohe raumliche und zeitliche Prazision, die mit Methoden der Lasermikroskopie erreicht werden kann. Das Verfahren der Zwei-Photonen-Anregung hat signifikante Vorzuge bei der Visualisierung biologischer Gewebe, allerdings ist der gezielte Entwurf intelligenter Sonden, die mit der Zellphysiologie kompatibel sind, nicht trivial. Dieser Aufsatz diskutiert die “chemischen” Herausforderungen bei der Entwicklung von Zwei-Photonen-Sonden.

Von Ein‐ zu Zwei‐Photonen‐Sonden: photoaktivierbare Reagentien, Aktuatoren und Photoschalter

From One-Photon to Two-Photon Probes: “Caged” Compounds, Actuators, and Photoswitches

The present invention relates to a X-ray and gamma-photon activable compound responding to the following formula (I). The present invention also relates to methods of synthesizing a compound according to the invention, and to an aqueous or physiological solution comprising at least one compound of the invention. The present invention also concerns a method of liberating a biologically active compound, said method involving the step of irradiating at least one compound, or at least one aqueous or physiological solution according to the invention. Finally, the present invention relates to a pharmaceutical composition comprising at least one compound, or at least one aqueous or physiological solution according to the invention.

X-ray and gamma-photon activable organic compounds, their preparation and their uses

Electromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth. High-energy stimuli, such as those employed for radiotherapy, are used to carry energy while molecular activation is provided by local energy conversion. This concept is applied to azobenzene, one of the most established photoswitches, to build a radioswitch. The radiation-responsive molecular system developed is used to trigger cytotoxic effect on cancer cells upon gamma-ray irradiation. This breakthrough activation concept is expected to expand the scope of applications of photosensitive systems and paves the way towards the development of original therapeutic approaches. 

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Guillaume Bort

Papers

From one-photon to two-photon probes: "caged" compounds, actuators, and photoswitches.

Von Ein‐ zu Zwei‐Photonen‐Sonden: photoaktivierbare Reagentien, Aktuatoren und Photoschalter

From One-Photon to Two-Photon Probes: “Caged” Compounds, Actuators, and Photoswitches

X-ray and gamma-photon activable organic compounds, their preparation and their uses

Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application