A platinum(IV) complex has the structure of Formula I.

##STR00001##

where X, X′, Y, Y′, and Z are each independently an electron donor ligand, R.sub.1˜R.sub.5 are each independently a functional group, L is the linker unit, and n is selected from the group of 0, a positive charge, and a negative charge. Various methods contain steps for manufacturing the platinum(IV) complex, for treating cancer, a tumor, or an infection in a subject with the platinum(IV) complex. A pharmaceutical composition contains the platinum(IV) complex.

In one aspect, compositions are described herein. A composition described herein comprises a nanoparticle, a therapeutic species, and a linker joining the nanoparticle to the therapeutic species. The linker joining the nanoparticle to the therapeutic species comprises a Diels-Alder cyclo-addition reaction product. Additionally, in some embodiments, the nanoparticle is a magnetic nanoparticle.

The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides. Other aspects are generally directed to methods of making or using such particles, kits involving such particles, or the like.

Compositions and methods for selective mTOR inhibition and/or increase of autophagy in a tissue of a subject have been developed for the treatment of cancer. Caged mTOR inhibitor prodrugs including photo-cleavable protecting groups are provided for selective chemotherapy through an optochemical treatment system. Pharmaceutical compositions of mTOR inhibitors that are deactivated (caged) with a photo-removable protecting group to controllably block the inhibitory activity of the inhibitor are provided. The photo-removable group is cleavable upon exposure to light irradiation, releasing the active inhibitor of mTOR signaling and autophagy at the site of irradiation. An exemplary caged mTOR inhibitor prodrug is a caged OSI-027 prodrug having a DEACM moiety bound thereto (cOSI-027). The cOSI-027 is activated in the region of a tumor by removal of the DEACM protecting group by exposure to light at 420 nm.

The present disclosure relates to an exosome comprising a photocleavable protein and a use thereof, and the exosome according to the present disclosure contains a fusion protein comprising a blue fluorescent protein (TagBFP), a photocleavable protein (mMaple3), and an exosome-specific marker protein (CD9), and it has been found that when light of 405 nm is irradiated to the exosome, the photocleavable protein, mMaple3 is cleaved and thereby the blue fluorescent protein in the exosome can be delivered into a target cell. In addition, it has been found that Cre protein in the exosome can be delivered into an animal organ, when light of 405 nm is irradiated to an exosome containing Cre fusion protein (Cre-mMaple3-CD9). Therefore, the exosome containing the photocleavable protein according to the present disclosure is expected to be useful in the protein treatment field by safely and efficiently delivering various therapeutic proteins into cells.

The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.

The syntheses of two phosphoramidite building blocks based on BNSF and BNSMB structures are disclosed. Furthermore, some common molecular intermediates have been designed and linked to the central biphenyl core of the two molecules, resulting in a versatile and cost-effective design. These compounds can be effectively introduced to DNA oligonucleotides via the well-established standard cyanoethylphosphoramidite chemistry on the nucleic acid synthesizer. Fragmentation of these BNSF- and BNSMB-functionalized DNA strands is achieved by both one-photon and two-photon photolysis of photoliable bonds of [2-(2-nitrophenyl)propoxy]carbonyl groups on BNSF and BNSMB molecules respectively, resulting in two short pieces of single-stranded DNAs. The versatile design and facile synthesis of these two-photon photocleavage phosphoramidite molecules are beneficial to synthetic chemists and photochemists for the development of new caged compounds which enables to introduce into oligonucleotides as light-triggered carriers via solid-phase synthesis for a wide range of applications in materials science, polymer, chemistry, biology and DNA nanoecthnology.

The present invention pertains to an inventive release mechanism for extracellular vesicle (EV)-mediated intracellular and intramembrane delivery of therapeutic polypeptides. More specifically, the invention relates to EVs comprising polypeptide constructs which comprise a therapeutic polypeptide releasably attached to an exosomal polypeptide. Furthermore, the present invention pertains to manufacturing methods, pharmaceutical compositions, medical uses and applications, and various other embodiments related to the inventive EVs.

The invention provides novel photolytic compounds and prodrugs, nanoparticles and compositions thereof, and methods of conducting photolysis mediated by triplet-triplet annihilation.

[Problem to be Solved]

Provided is a delivery carrier into the cell having high antioxidant activity, intracellular absorbability, intracellular disintegration property, stability and safety, which have high delivery property of the active ingredient to cell and living tissues.

[Solution]

The delivery carrier into cells includes a vitamin derivative with co-activation of both autophagy-related genes and protease synthesis genes, a polymer molecule containing stimulatory reactivity, an emulsion stabilizer, an active ingredient, and a lipid, thereby providing a delivery carrier into cells with high delivery properties of the active ingredient to cells and living tissues.