Structure Design and Functionalization strategies of Silica Nanoparticle for Dual Modal Imaging and Specific Targeting

Abstract

Nanostructured materials exhibit unique and useful properties which can be applied to various areas. In particular, imaging science and technology has actively been adapting nanoparticles as imaging agents and tracking probes. Advances in imaging techniques allow for accurate detection of early-stage of cancer and targeted therapies based on the cancer-specific markers. However, among all the imaging modalities, no single modality is perfect to meet all the requirements in medical applications. Each imaging modality has certain advantages as well as limitations, and the choice for an imaging modality, or combination of techniques, is determined by the specific biological questions being asked. Developing dual modal imaging probes and combining the advantages of these modalities can offer synergistic advantages in providing more valuable diagnostic information and treatment strategies. Hence, we demonstrated that multimodal imaging nanoparticle combined with optical imaging and nuclear imaging has merit for potential imaging of various biological targets and process with high sensitivity and specificity without the tissue penetrating limit. It is based on the use of fluorescent dye-doped silica nanoparticles (F-silica NPs) as the core material of optical imaging contrast agent. The silica NPs have the advantages that their surface can be easily modified according to applications. Furthermore, we have also conjugated the well-known PET imaging probe 68Ga and targeting moiety, Herceptin on the F-silica NPs, which will allow specific targeted bio imaging independent of tissue depth. This multifunctional nanoprobe is capable of optical imaging which is also detectable by PET after cell targeting. Moreover, in order to impart stealth properties to the F-silica NPs, we conjugated heterobifunciotnal PEG on F-silica NPs. Also we confirmed the effect of PEG chain length on the resulting particle size, surface charge and 68Ga labeling efficiency of F-silica NPs. The method of using PEG 10,000 on 1 v/v% APTS modified F-silica NPs was effective surface modification strategy for effective 68Ga labeling. Therefore, functionalized F-silica NPs are promising candidate as an efficient imaging probe of PET technique. We will further discuss the strategy of ligand conjugation for targeting without losing its functionality after attachment to the F-silica NPs.