Self-assembling drug amphiphiles and methods for synthesis and use

摘要

The present invention provides herein the design of monodisperse, amphiphilic anticancer drugs—which are now termed “drug amphiphiles” (DAs)—that can spontaneously associate into discrete, stable supramolecular nanostructures with the potential for self-delivery (no additional carriers are needed). The quantitative drug loading in the resulting nanostructures is ensured by the very nature of the molecular design. The DA is a composition comprising: D-L-PEP; wherein D is 1 to 4 hydrophobic drug molecules which can be the same or different; L is 1 to 4 biodegradable linkers which can be the same or different; and PEP is a peptide that can spontaneously associate into discrete, stable supramolecular nanostructures. In an alternate embodiment, the DA composition also comprises a targeting ligand (T). Methods of making DA molecules, as well as their use in treatment of disease are also provided.

主权项

1. A composition comprising:
D-L-PEP; wherein D is 1 to 4 hydrophobic drug molecules, wherein the drug molecules are chemotherapeutic agents having a water solubility of less than 10 mg/ml; L is 1 or more biodegradable linkers selected from the group consisting of disulfanylcarbonate (etcSS) and disulfanylbutanoate (buSS); and PEP is a hydrophilic peptide selected from the group consisting of GVQIVYKK (SEQ ID NO: 1), CGVQIVYKK (SEQ ID NO: 6), and VQIVYK (SEQ ID NO: 9).