| abstract |
In accordance with one or more embodiments, the present invention provides a new strategy for an improved target-specific drug delivery that utilizes enhanced internalization of therapeutic conjugates by in situ complexation driven by bioorthogonal click chemistry, which is defined herein as "click therapy". This novel two-step/two-component system for intracellular delivery of therapeutics is based on the induced internalization of cross-linked and clustered mAb to target receptors of interest, including, for example, HER2 receptors. The system provides target-specific, and optionally, image-guided drug delivery, and highly efficient internalization and accumulation of chemotherapeutics in the target cells of interest. The present invention provides in situ complexation of two or more delivery components by the bioorthogonal click reactions between multiple azido-functionalized or tetrazine functionalized mAb and multiple cyclooctyne-functionalized nanocarriers, or trans- cyclooctene functionalization, and bovine serum albumin (BSA) substituted with chemotherapeutics, such as paclitaxel. The present invention provides copper-free, strained- promoted, bioorthogonal click chemistry for therapy. |