Surface Functionalized Magnetic Nanoparticles for Cancer Therapy Applications

Despite recent advances, cancer remains the second leading cause of deaths in the United States. Magnetic nanoparticles have found various applications in cancer research as drug delivery platforms, enhanced contrast agents for improved diagnostic imaging, and the delivery of thermal energy as standalone therapy. Iron oxide nanoparticles absorb the energy from an alternating magnetic field and convert it into heat through Brownian and Neel relaxations. To better utilize magnetic nanoparticles for cancer therapy, surface functionalization is essential for such factors as decreasing cytotoxicity of healthy tissue, extending circulation time, specific targeting of cancer cells, and manage the controlled delivery of therapeutics. In the first study, iron oxide nanoparticles were coated with a poly(ethylene glycol) (PEG) based polymer shell. The PEG coating was selected to prevent protein adsorption and thus improve circulation time and minimize host response to the nanoparticles. Thermal therapy application feasibility was demonstrated in vitro with a thermoablation study on lung carcinoma cells. Building on the thermal therapy demonstration with iron oxide nanoparticles, the second area of work focused on intracellular delivery. Nanoparticles can be appropriately tailored to enter the cell and deliver energy on the nanoscale eliminating individual cancer cells. The underlying mechanism of action is still under study, and we were interested in determining the role of reactive oxygen species (ROS) catalytically generated from the surface of iron oxide nanoparticles in this measured cytotoxicity. When exposed to an AMF, the nanoscale heating effects are capable of enhancing the Fenton-like generation of ROS determined through a methylene blue degradation assay. To deliver this enhanced ROS effect to cells, monosaccharide coated nanoparticles were developed and successfully internalized by colon cancer cell lines. Upon AMF exposure, there was a measured increase in cellular ROS and apoptosis that was attributed to lysosomal disruption since the surface functionalization selected inhibited the Fenton-like surface chemistry. To overcome this surface inhibition, a biodegradable poly(β-amino ester) (PBAE) polymer coating was synthesized to deliver bare iron oxide to intracellular components. Delivering enhanced ROS to cancer cells is a promising new route of therapy that deserves future studies

Block Copolymer Self-Assembled and Cross-linked Nanoassemblies for Combination Delivery of Iron Oxide and Doxorubicin

We describe the development of nanoscale polymer drug carriers for the combinational delivery of an anticancer drug (doxorubicin: DOX) along with super paramagnetic iron oxide nanoparticles (IONPs). The drug molecules were electrostatically loaded into both block copolymer self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs). Both nanoassemblies entrapped DOX and IONPs either individually or in tandem, maintaining sub-100 nm diameter. The IONP-loaded nanoassemblies generated heat in the presence of an alternating magnetic field (AMF). Incorporation of the drug payload, DOX, showed no adverse effects on the heating profile. Drug release from the SNAs and CNAs was accelerated as temperature increased from the normal body temperature (37°C) to a mild hyperthermic condition (40 ~ 42°C). CNAs released DOX faster than SNAs regardless of an incubation temperature. CNAs co-entrapped IONPs and DOX were more stable than SNAs in aqueous solutions for five days. These results suggest that block copolymer cross-linked nanoassemblies provide viable delivery platforms for combination delivery of inorganic molecules, anticancer drugs, and potentially other various biologically active substances

Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles

PURPOSE: To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs). METHODS: Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs). RESULTS: CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (\u3e 400 nm) in all aqueous media tested. No cytotoxicity was observed in a mouse brain endothelial-derived cell line (bEnd.3) exposed to CNA-IONPs up to 10 mg/mL for 30 h. Citrate-IONPs (\u3e 0.05 mg/mL) reduced cell viability after 3 h. CNA-IONPs retained the superparamagnetic properties of entrapped IONPs, enhancing T2-weighted magnetic resonance images (MRI) at 0.02 mg/mL, and generating heat at a mild hyperthermic level (40 ~ 42°C) with an alternating magnetic field (AMF). CONCLUSION: Compared to citric acid coating, CNAs with a cross-linked anionic core improved particle stability and biocompatibility of IONPs, which would be beneficial for future MRI and AMF-induced remote hyperthermia applications

Cassava improvement in sub-Saharan Africa: contributions of IITA and its partners

Cassava is well recognized for its capacity to address food needs of vulnerable communities in unstable environments in SSA. IITA and colleagues in African NARS, in collaboration with CIAT and ARIs have played leading roles in the development of improved cassava varieties which are disease and pest resistant, early maturing, and high yielding. Through a combination of conventional and new approaches, over 400 cassava genotypes have been developed. The characteristics of the new generation of cassava germplasm broke what had been an apparent yield barrier in cassava improvement increasing yields in many locations by at least 50–100% without the use of fertilizer. The improved germplasm is shared with NARS within the region as specific genotypes or improved seed populations for evaluation and selection under local conditions. Improvement programs in Africa that received these materials have tested them under local conditions, selected varieties that outperform local varieties, and released them to farmers in virtually every major cassava producing country. Today, about 30% of the area cropped with cassava in Africa is planted with improved varieties. Without the introduction of more productive cultivars with multiple diseases and pest resistance, the effective biological control of the cassava mealybug and, to a certain extent, of the green mite, cassava production in SSA would be 50% or less of what it is today. That translates to over 13 million tons of dry cassavayear, enough to meet the calorie requirements of 65 million people. The significant gains in the crop’s output in farmers’ fields are not only contributing to the African diet but also propelling commercialization of the crop. This paper highlights contributions to cassava improvement in SSA since 1970 by IITA and its partners, and suggests areas needing strengthening in the drive to produce better crop varieties for different regions and enduses in Africa