Folic acid-chitosan@gold nanocomposite for potential diagnostic and therapeutic applications

Abstract

Biosynthesis of nanomaterials attracts great attention because environmentally benign conditions are used. Investigations have shown that biomolecules and organisms can selectively recognize inorganic surfaces and can also serve as substrates for inorganic nucleation and growth. Folic acid (FA) is a useful cancer cell targeting ligand which can be covalently conjugated to chitosan (CHI) molecules while retaining a high affinity to the folate receptor. FA-CHI can also serve as structure-directing agent for the formation of metal nanocrystals. Gold nanocrystals possess unique chemical and physical properties which can offer new opportunities for early diagnosis and therapeutics. In this investigation, a one-pot approach was used for the synthesis of FA-CHI@Au nanocomposite (NC). FA-CHI was obtained by the reaction of carboxyl end groups of folic acid with the amino groups of chitosan. A HAuCl4 solution was added into a premixed solution of FA-CHI at 90ºC and the reaction took place for 3h. The NC formed had a gold metal core of anisotropic structures with many irregular branches. The shell of NC was a layer of FA-CHI (10 nm in thickness). The diameter of the NC was about 75 nm and the zeta potential was +37.5 mv in pure water. Upon excitation with a red visible laser (633 nm), the NC fabricated elicited greatly improved surface enhanced Raman scattering signals when using Rhodamine B as Raman reporter. The NC was able to target tumor biomarkers such as folate receptors on cancer cells owing to the FA on the surface of NC. The FA-CHI shell provided good stability for both Au nanoparticles and small Raman reporters and should improve both in vitro and in vivo usability of FA-CHI@Au nanocomposite.