2013 IR&D Annual Report

Drug-loaded Magnetic Calcium Phosphate Nanoparticles (MCaP NPs) for Cancer Therapy, 01-R8400

Principal Investigators
XingGuo Cheng
Qingwen Ni
Hakan Basagaoglu

Inclusive Dates: 07/01/13 – Current

Background — One in four deaths in the United States is attributable to cancer, with prostate and breast cancers the most common forms. The current systemic chemotherapy drug treatment of cancer has two major disadvantages: severe side effects and drug resistance. There is a clear need to develop a novel cancer therapy to effectively treat cancer with fewer side effects. The objective of this project is to develop newly formulated MCaP-based magnetic NPs as a combinational therapy for advanced breast/prostate cancer treatment. Both magnetic induction heating (hyperthermia-based therapy) and NP chemotherapy will be used to kill cancer. Targeted dual therapy can effectively treat cancer because of its possible synergistic effect and unique targeting mechanism.

Approach — This project has three objectives: synthesize and characterize MCaP NPs and investigate drug loading and release; evaluate the efficacy of MCaP NPs combination therapy in vitro and determine the minimum concentration of MCaP NPs required for tumor hyperthermia; and evaluate MCaP NP accumulation in a xenograft tumor mice model and treatment efficacy in vivo.

4 images involving MCaP NP formulation
A. Particle size of a MCaP NP formulation. B. EDX analysis of a MCaP NP formulation that has high loading of iron oxide inside the CaP. *Note: Results do not include elements with Z<11 (Na). C. Purchased bench top IHG061A induction machine (coils of different sizes are available). D. The induction heating capabilities of our prepared MCaP NP suspension in water (18.6 mg/mL). The MCaP NPs can be heated to 60°C within 6 min.

Accomplishments — The MCaP NP formulation was improved by fine-tuning the amount of CaP encapsulating the iron oxide magnetic NPs. As shown in Figure 1A-B, at similar NP size (~180 nm), MCaP with iron loading up to 94 wt percent can be formed. By reducing the amount of CaP, more iron oxide was encapsulated inside and thus the magnetic heating capability will be increased. NP formulation with the highest Fe loading was heated up using alternating magnetic field (AMF). As shown in Figure 1C-D, MCaP NPs can be heated up to 60°C within six minutes. Drug-loaded NPs were magnetically separated and analyzed by UV-vis. In the next phases, these targeted, drug-loaded NPs will be tested in vitro and in vivo to ascertain if they are viable for cancer treatment.

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