| 摘要 |
ABSTRACT - 601550 The disclosure relates to a hyperbranched dendritic polyanionic macromolecule of sulphated polyglycerol for targeted delivery of diagnostic and therapeutic effector molecules to the cytoplasm and nucleus of proliferating and activated cells. The disclosure also relates to compositions for targeting of intracellular molecules involved in proliferation and protein synthesis of activated cells using polyanionic multivalent macromolecules. In particular aspect, multiple sulfate groups linked to polyglycerol are specifically targeted to the cytoplasm and nucleus of proliferating and activated cells. Particularly disclosed is the use of a pharmaceutical composition comprising a compound of the formula P(OSO3-M+)n(L-G-E)m, wherein P is a polyol macromolecule in which a number n of hydroxyl groups is substituted by sulfate groups OSO3-M+, n being a number > 10, M is a cationic inorganic or organic counter ion to the anionic sulfate group, E is a diagnostic effector molecule selected from the group of fluorescent dyes or chelators for radioactive or paramagnetic metals or a therapeutic effector molecule selected from the group of cytostatics, anti-angiogenetic drugs, photosensitizers and siRNAs, L is a linker or spacer between P and E, G is a reactive group for the covalent attachment between L and E, and m is a number of 1-100, for the preparation of a medicament for treating a disease related to activated NF-kappaB and/or AP-1 and/or elevated synthesis of TGF-beta by intracellular uptake of the compound of the formula P(OSO3-M+)n(L-G-E)m into activated cells or proliferative cells and by inhibiting NF-kappaB and/or AP-1 and/or TGF-beta synthesis in said cells. |
