Design of thermally responsive, recombinant polypeptide carriers for targeted drug delivery.
In this article, we review recombinant DNA methods for the design and synthesis of amino acid-based biopolymers, and briefly summarize an approach, recursive directional ligation (RDL), that we have employed to synthesize oligomeric genes for such biopolymers. We then describe our ongoing research in the use of RDL to synthesize recombinant polypeptide carriers for the targeted delivery of radionuclides, chemotherapeutics and biomolecular therapeutics to tumors. The targeted delivery system uses a thermally responsive, elastin-like polypeptide (ELP) as the drug carrier to enhance the localization of ELP-drug conjugates within a solid tumor that is heated by regional hyperthermia. In the context of this drug delivery application, we discuss the design of ELPs and their recombinant synthesis, which enables the molecular weight and the thermal properties of the polypeptide to be precisely controlled. Finally, our results pertaining to the in vivo targeting of tumors with ELPs are briefly summarized.
Chilkoti
Ashutosh
A
Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA. chilkoti@duke.edu
Dreher
Matthew R
MR
Meyer
Dan E
DE
D000595:Amino Acid Sequence; D001483:Base Sequence; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000235:genetics; D020539:Sequence Analysis, Protein / Q000379:methods
D004337:Drug Carriers; D010455:Peptides; D011994:Recombinant Proteins