Abstract
Nanomaterials can be synthesized from a wide range of material systems in numerous morphologies, creating an extremely diverse portfolio. As result of this tunability, these materials are emerging as a new class of nanotherapeutics and imaging agents. One particularly interesting nanomaterial is the gold nanoparticle. Due to its inherent biocompatibility and tunable photothermal behavior, it has made a rapid transition from the lab setting to in vivo testing. In most nanotherapeutic applications, the efficacy of the agent is directly related to the target of interest. However, the optimization of the AuNP size and shape for efficacy in vitro, prior to testing in in vivo models of a disease, has been largely limited to two dimensional monolayers of cells. Two dimensional cell cultures are unable to reproduce conditions experienced by AuNP in the body. In this article, we systematically investigate the effect of different properties of AuNP on the penetration depth into 3D cell spheroids using two-photon microscopy. The 3D spheroids are formed from the HCT116 cell line, a colorectal carcinoma cell line. In addition to studying different sizes and shapes of AuNPs, we also study the effect of an oligo surface chemistry. There is a significant difference between AuNP uptake profiles in the 2D monolayers of cells as compared to the 3D cell spheroids. Additionally, the range of sizes and shapes studied here also exhibit marked differences in uptake penetration depth and efficacy. Finally, our results demonstrate that two-photon microscopy enables quantitative AuNP localization and concentration data to be obtained at the single spheroid level without fluorescent labeling of the AuNP, thus, providing a viable technique for large scale screening of AuNP properties in 3D cell spheroids as compared to tedious and time consuming techniques like electron microscopy.
Highlights
Nanomaterials hold tremendous promise for targeted delivery of generation cancer therapies[1,2,3]
We established conditions suitable to grow cell spheroids approximately 400μm in diameter. This diameter was selected based on the field of view of the two-photon microscope. 2D cell cultures for imaging were generated in standard cell culture plates by seeding HCT116 cells at densities which resulted in approximately 80% confluency after 3 days of culture
To determine the impact of the nanomaterials on the cell cultures, we focused on three metrics: growth rate, uptake efficiency, and penetration depth into the spheroid
Summary
Nanomaterials hold tremendous promise for targeted delivery of generation cancer therapies[1,2,3]. These materials can play numerous roles in an overall nanotherapeutic design strategy, from acting as a protective encapsulant to playing the role of the actual therapeutic agent. One unique class of nanotherapeutics is the gold nanoparticle (AuNPs). AuNPs have been used as drug carriers[4], photothermal agents[5], contrast agents[6] and radiosensitizers[7].
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