Novel photocleavable drug conjugates for forming drug depots comprise drugs attached to photocleavable groups. In one embodiment, the drug is linked via photocleavable group(s) to a polymer chain to form a photocleavable drug-polymer conjugate that generally forms the depot matrix. In another embodiment, the drug is crosslinked via photocleavable group(s) to themselves to form a photocleavable drug conjugate that generally forms the depot.

Provided is a system for drug delivery comprising a modified poly (amidoamine) (PAMAM) comprising a photo-cleavable compound bound to one or more active agents to form a nanocomplex. Also provided is a method of treating a subject comprising administering the PAMAM nanocomplex and irradiating the nanocomplex at the target site with a light source. In particular, the modified PAMAM is a DEACM-modified PAMAM or a BODIPY-modified PAMAM. Also provided is a method for screening for PAMAM-coumarin-active agent nanocomplexes.

Triazenes and methods of producing diazonium species from said traizenes using ultraviolet (UV) light, which provide a fast, easy, stable, scalable, and selectively-triggerable means of modifying aromatic nucleophiles, including those on protein surfaces. Thus, the present invention also includes triazenes for use as bioconjugates, e.g., for use in protein modification, for use as probes (including but not limited to detectable probes such as fluorescent probes), protein crosslinking, etc.

The field of various phototriggered drug release and photoreactions, including reactions generally based on triplet-triplet energy transfer with light excitation at long wavelengths. Systems and methods for absorbing energy in a photosensitizer, and methods for making or using such systems, kits including such systems. The systems and methods comprise transferring that energy by triplet-triplet energy transfer to cleave a cleavable or other active moiety, for instance, in order to cause the release of a releasable moiety. In some cases, these may be contained within a suitable carrier material, for example, a particle or a micelle. Such systems and methods may be used in a variety of applications, including various biological or physical applications. For example, such systems and methods may be useful for delivering drugs or other releasable moieties to regions of a subject.

In one aspect, the present disclosure provides a compound of the formula: In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. ##STR00001##

Aspects of the disclosure include compositions, devices, systems and methods for optogenetic modulation of action potentials in target cells. The subject devices include light-generating devices, control devices, and delivery devices for delivering light-responsive polypeptides, or nucleic acids encoding same, to target cells. The subject compositions and systems include light-activated polypeptides, nucleic acids comprising nucleotide sequences encoding these polypeptides, as well as expression systems that facilitate expression of these polypeptides in target cells. Also provided are methods of using the subject devices and systems to optogenetically manipulate action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or animal subject.

A novel optogenetic system, including constructs and methods, is provided based on the interaction of Rhodopseudomonas palustris BphP1 and Rhodopseudomonas palustris PpsR2 or a non-dimerizing variant thereof.

A system (and associated method) for treating a human or animal body. The system has a photoactivatable drug for treating a first diseased site, a first pharmaceutically acceptable carrier including one or more phosphorescent or fluorescent agents which are capable of emitting an activation energy into the body which activates the photoactivatable drug, a first device which infuses the first diseased site with a photoactivatable drug and the first pharmaceutically acceptable carrier, a first energy source which irradiates the diseased site with an initiation energy to thereby initiate emission of the activation energy into the body, and a supplemental treatment device which administers one or both of a therapeutic drug or radiation to the body at a second diseased site or the first diseased site, to provide an immune system stimulation in the body.

In one aspect, a chemically-modified siRNA for reversible photo-controlled gene silencing is provided. In one embodiment, one or more nucleotides the sense strand of the siRNA are replaced with a spacer comprising an azobenzene or derivative thereof. The azobenzene or derivative thereof undergoes isomerization between the trans-configuration and the cis-configuration in the presence of light from a light source and the siRNA optionally has higher RNA silencing activity when the azobenzene or derivative thereof is in the trans-configuration compared to the cis-configuration. In other aspects, the chemically-modified siRNAs may, for example, be useful as both therapeutics and research tools.

Disclosed herein is a compound for use in a composition applied to a blood vessel, wherein the compound softens and/or disrupts the crystalline matrix of calcified plaque. Methods of treatment comprising applying the disclosed composition are also disclosed. Plaque-softening compounds are also disclosed.