(604e) Efficient, Convenient, and Minimally Invasive Delivery of Gold Nanoparticles for Diagnosis of Early Stage Cancer Using Optical Coherence Tomography

Optical coherence tomography (OCT) is an optical diagnostic tool that can detect abnormal lesions with micrometer resolutions in almost real time. However, detecting early-stage cancer using OCT requires sufficient contrast in tissue. Gold nanoparticles (Au NPs) are a promising OCT contrast agent because they are biocompatible and easy to synthesize in desired sizes/shapes which determine the physico-optical properties of Au NPs. While topical delivery of Au NPs offers many potential advantages over systemic administration, inefficient penetration through outer tissue layers (e.g., stratum cornea, SC) and poor distribution of Au NPs inside tissue are major hurdles to overcome.

The hypothesis that Au NPs formulated in dissolvable microneedles (dMNs) can be efficiently delivered into target epithelial layers and further efficiently dispersed by mild ultrasound (US) (i.e., multi-modal delivery), generating significantly improved optical contrast, was explored in this study. PEGylated Au NPs (70 nm diameter) were incorporated in polysaccharide-based MNs (200 μm height). Au NP-containing dMNs were then applied on hamster cheek pouch in vivo, where early dysplasia had been induced by a carcinogen, followed by applying US at a diagnostic level (1 MHz at 0.3 W/cm2). The multimodal Au NP delivery using dMN and US resulted in 33 % and 20 % increase in scattering intensity in dysplasia and normal tissues, respectively, which was imaged by spectral domain (SD)-OCT and confirmed by histological assessment. The results clearly demonstrated significantly and disease-specifically enhanced optical contrast by topically administering Au NPs via efficient, convenient, and minimally invasive multi-modal delivery.