Engineered Polymer-Transferrin Conjugates as Self-Assembling Targeted Drug Delivery Systems.

Engineered Polymer-Transferrin Conjugates as Self-Assembling Targeted Drug Delivery Systems. Biomacromolecules. 2017 Mar 28;: Authors: Makwana H, Mastrotto F, Magnusson JP, Sleep D, Hay J, Nicholls KJ, Allen S, Alexander C Abstract Polymer-protein conjugates can be engineered to self-assemble into discrete and well-defined drug delivery systems which combine the advantages of receptor targeting and controlled drug release. We designed specific conjugates of the iron-binding and transport protein, transferrin (Tf), to combine the advantages of this serum-stable protein as a targeting agent for cancer cells with self-assembling polymers to act as carriers of cytotoxic drugs. Tf variants were expressed with cysteine residues at sites spanning different regions of the protein surface and the polymer conjugates grown from these variants were compared with polymer conjugates grown from non-selectively derivatised sites on native Tf. The resulting synthetic biopolymer hybrids were evaluated for self-assembly properties, size and topology, ability to carry an anti-cancer drug (paclitaxel) and cytotoxicity with and without a drug payload in a representative human colon cancer cell line. The results demonstrated that the engineered Tf variant polymer conjugates formed better-defined self-assembled nanoparticles than the non-selectively derivatised conjugates and showed greater efficacy in paclitaxel delivery. A polymer conjugate grown from a s...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research