ABSTRACT
This study describes the synthesis, surface analysis, and biological evaluation of bioactive titanium surfaces. The aim was to achieve an improved effect on osteoinduction in dental and orthopedic implants. For this purpose, a chemistry was developed, which allows to bind the bioactive cyclopeptide cRGDfK covalently to biomedically used titanium via polyethylene glycol linkers of different lengths. The chemical process is practicable, robust, and metal-free. The resulting chemically modified titanium plates show improved osteoinductive properties. The modification with cRGDfK targets the integrin αvß3, which is highly expressed in osteoblasts and is essential for many basic functions in the development of bone tissue. The successful immobilization of cRGDfK on titanium surfaces has been demonstrated by contact angle measurements and X-ray photoelectron spectroscopy. We show in in vitro studies that the presence of the cRGDfK peptide on titanium surfaces has a positive effect on bone formation.
Subject(s)
Biocompatible Materials , Titanium , Biocompatible Materials/metabolism , Biocompatible Materials/pharmacology , Coated Materials, Biocompatible/chemistry , Oligopeptides/chemistry , Osteoblasts , Surface Properties , Titanium/chemistry , Titanium/pharmacologyABSTRACT
A combination of mutasynthesis, precursor-directed biosynthesis and semisynthesis provides access to new ansamitocin derivatives including new nanostructured particle-drug conjugates. These conjugates are based on the toxin ansamitocin and superparamagnetic iron oxide-silica core shell particles. New ansamitocin derivatives that are functionalized either with alkynyl- or azido groups in the ester side chain at C-3 are attached to nanostructured iron oxide core-silica shell particles. Upon exposure to an oscillating electromagnetic field these conjugates heat up and the ansamitocin derivatives are released by a retro-Diels-Alder reaction. For example, one ansamitocin derivative exerts strong antiproliferative activity against various cancer cell lines in the lower nanomolar range while the corresponding nanostructured particle-drug conjugate is not toxic. Therefore, these new conjugates can serve as dormant toxins that can be employed simultaneously in hyperthermia and chemotherapy when external inductive heating is applied.
