Integration of iron oxide nanoparticles and polyaspartamide biopolymer for MRI image contrast enhancement and an efficient drug-delivery system in cancer therapy.

We integrate superparamagnetic iron oxide nanoparticles with polyaspartamide (PA) biopolymer to form a biological construct that functions as a tracking, targeting and drug-delivery system for cancer diagnosis and therapy. Iron oxide nanoparticles with uniformly distributed average spherical diameters of around 10 nm and superparamagnetic characteristics play a key role in increasing the transverse 1/T 2 relaxation rate or darkening the T 2-weighted MR image for cancer diagnosis using MRI. In in vitro MRI testing on cancer cells, the MR images of samples with the bio-constructshow a much clearer contrast effect than those of controls. The PA biopolymer plays an essential role in enhancing the hydrophilicity and biocompatibility of the bio-construct. In addition, as a multifunctional polymer, PA is conjugated with biotin and doxorubicin (Dox) functional groups to enhance targeting and impairment of cancer cells. In in vivo testing on cancer tumors, injection with the bio-construct decreased the magnitude of cancer tumor volume growth by three times compared with that of uninjected controls. The physicochemical characteristics of the bio-construct and the roles of biotin and Dox functional groups are examined and discussed in detail.

Self-assembled nanoaggregates based on polyaspartamide graft copolymers for pH-controlled release of doxorubicin.

A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazone (Hyd) segments on a PASPAM backbone. The hydrazone group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The mean diameter of the self-aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20%. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatment.