(340a) Estrogen Receptor-Targeted Multiplexing Photoacoustic Polymeric Nanoparticles for Diagnostic and Treatment of Breast Cancer
AIChE Annual Meeting
2018
2018 AIChE Annual Meeting
Particle Technology Forum
Functional Nanoparticles
Tuesday, October 30, 2018 - 12:30pm to 12:55pm
C.Nino-Vargas1, E.Blatchford-Rodriguez1, Z.Begnell1, R.Khalid1, G.Petruncio2, M.Paige2, C.Salvador-Morales1
1Bioengineering Department, George Mason University, 4400 University Drive, Fairfax, Virginia, 22030, 2Chemistry Department, George Mason University, 4400 University Drive, Fairfax, Virginia, 22030.
Introduction. Breast cancer is the second cause of death in women after lung cancer, with approximately 41,000 breast cancer deaths expected this year [1]. Systemic chemotherapy is one of the most common approaches to therapy, but its systemic toxicity is a major drawback that limits chemotherapeutic utility and effectiveness [2]. Another significant problem is the generation of the multidrug resistance phenomenon, which, among other factors, arises from inhomogeneous distribution of the drug within the tumor [3]. A recent focus of cancer research is on developments of theranostic systems capable of providing diagnostic imaging and therapeutic functions simultaneously. An emerging scientific and clinical consensus is that theranostic devices may provide several medical benefits including: a) molecular imaging functionalities to help physicians track drug distribution within the solid tumor, b) valuable guidance on selection of a safe and efficacious dose, and c) real-time objective monitoring of therapeutic response. The multiplexing photoacoustic capability of these nanovehicles will render substantial anatomical, physiological and functional information of the breast cancer tumor.
Here, we report the design and synthesis of a novel targeted cancer theranostics device for breast cancer treatment that leverages the highly tunable internal properties of Patchy Polymeric Nanoparticles (PPNPs). Estrogen Receptor-Targeted Patchy Polymeric Nanoparticles loaded with Indocyanine Green (ICG) and IR-26 consist of poly (lactic-co-glycolic acid) (PLGA) and lipid-PEGylated-Estrone. PLGA and ICG are biocompatible and FDA-approved biomaterials. These nanoparticles have unique patch-core-shell structural features: hollow core and patchy surface. The particleâs patchy surface can be utilized to enhance tumor targeting because of the high concentration of targeting moieties in one region of the particleâs surface.
Materials and Methods. The surface of our nanoparticles is functionalized with Lipid-PEGylated-Estrone molecules that will bind specifically to estrogen receptors that are over-expressed in breast cancer cells. We performed a comprehensive characterization of the targeting moiety using Nuclear Magnetic Resonance (NMR), Matrix Assisted Laser Desorption/Ionization (MALDI) and High Performance Liquid Chromatography (HPLC). Our results show that we successfully synthesized the targeting moiety. Next, we synthesized the targeted nanoparticles using a modified single emulsion method previously published [4]. Moreover, we characterized these nanoparticles with different experimental techniques including Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), Absorption and Near-IR Spectroscopy. Our results show that these particles have an average hydrodynamic diameter of 165 nm ± 5 nm. Also, the particlesâ size is stable for months in frozen and lyophilized storage conditions. Furthermore, we assessed the absorption ability of these nanoparticles in the Near-IR region of the electromagnetic spectrum. These nanoparticles present an absorption peak at 786 nm and 895 nm wavelength. TEM shows the spherical morphology of these nanoparticles. Additionally, we evaluated the cellular toxicity of the engineered nanoparticles at different concentrations. We observed that these nanoparticles are not toxic as expected since PLGA and ICG are biocompatible, and IR is enveloped by the polymeric matrix. Moreover, we evaluated the cell uptake of untargeted and targeted nanoparticles at 2 hrs. and 24 hrs. time points using T-47D breast cancer cells. We observed that targeted nanoparticles are avidly taken by breast cancer cells at both 2hrs and 24 hrs. However, there cell uptake at 24 hrs. is higher than that at 2hrs. The assessment of the photoacoustic performance and in vitro cellular uptake of these nanoparticles is underway. Future experiments will be carried out to evaluate their in vivo photoacoustic performance. Equally important, we have carried out drug release studies to determine the drug release profile of these nanoparticles. Our most recent studies demonstrate that these nanoparticles release 70% of the drug over a month.
Conclusions: These preliminary results show the feasibility of engineering multiplexing photoacoustic theranostic carriers for breast cancer treatment. Thus, these theranostics have the potential to provide meaningful information about the tumor vasculature because of their ability to penetrate deep into tissue while killing at the same time tumor cells selectively.