Multimodal Imaging Nanoparticles Derived from Hyaluronic Acid for Integrated Preoperative and Intraoperative Cancer Imaging.

William M Payne,Denis Svechkarev,Tanner K Hill,Megan B Holmes,Balasrinivasa R Sajja,Aaron M Mohs

doi:10.1155/2017/9616791

Multimodal Imaging Nanoparticles Derived from Hyaluronic Acid for Integrated Preoperative and Intraoperative Cancer Imaging.

William M Payne, Denis Svechkarev + Show 4 more

Open Access

https://doi.org/10.1155/2017/9616791

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Abstract

Surgical resection remains the most promising treatment strategy for many types of cancer. Residual malignant tissue after surgery, a consequence in part due to positive margins, contributes to high mortality and disease recurrence. In this study, multimodal contrast agents for integrated preoperative magnetic resonance imaging (MRI) and intraoperative fluorescence image-guided surgery (FIGS) are developed. Self-assembled multimodal imaging nanoparticles (SAMINs) were developed as a mixed micelle formulation using amphiphilic HA polymers functionalized with either GdDTPA for T1 contrast-enhanced MRI or Cy7.5, a near infrared fluorophore. To evaluate the relationship between MR and fluorescence signal from SAMINs, we employed simulated surgical phantoms that are routinely used to evaluate the depth at which near infrared (NIR) imaging agents can be detected by FIGS. Finally, imaging agent efficacy was evaluated in a human breast tumor xenograft model in nude mice, which demonstrated contrast in both fluorescence and magnetic resonance imaging.

Highlights

Surgical resection remains the most promising treatment strategy for many forms of cancer
In this study we report the optimization of an hyaluronic acid- (HA-)based nanoparticle formulation for integrated preoperative magnetic resonance imaging (MRI) and intraoperative near infrared fluorescence imaging, termed self-assembled multimodality imaging nanoparticles (SAMINs)
We demonstrate that HA-based nanoparticles incorporating both gadolinium and a fluorophore can provide contrast enhancement for both imaging modalities, with the goal of providing better surgical guidance for tumor resection and improving prognosis

Summary

Introduction

Surgical resection remains the most promising treatment strategy for many forms of cancer. Augmenting the efficacy of surgical intervention in cancer treatment through technologies aiming to improve contrast, such as image-guided surgery, can improve the prognosis and outcome of cancer treatment [1,2,3]. Residual cancerous tissue after surgery contributes to tumor recurrence and is a limitation of surgical efficacy, reducing the chances for long-term survival. Complete removal of cancerous tissue during the initial surgical intervention is critical to improved prognosis. As reported by us [1, 5, 6] and others [3, 7], the use of near infrared fluorescence contrast agents, both FDA-approved (i.e., indocyanine green (ICG)) and experimental, can guide surgeons in real-time, delineating tumor boundaries and improving outcome [2, 3]

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Discussion

Conclusion