Nanotechnology applications in surgical oncology

Abstract

Surgery is currently the most effective and widely used procedure in treating human cancers, and the single most important predictor of patient survival is a complete surgical resection. Major opportunities exist to develop new and innovative technologies that could help the surgeon to delineate tumor margins, to identify residual tumor cells and micrometastases, and to determine if the tumor has been completely removed. Here we discuss recent advances in nanotechnology and optical instrumentation, and how these advances can be integrated for applications in surgical oncology. A fundamental rationale is that nanometer-sized particles such as quantum dots and colloidal gold have functional and structural properties that are not available from either discrete molecules or bulk materials. When conjugated with targeting ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target malignant tumor cells and tumor microenvironments with high specificity and affinity. In the "mesoscopic" size range of 10-100 nm, nanoparticles also have large surface areas for conjugating to multiple diagnostic and therapeutic agents, opening new possibilities in integrated cancer imaging and therapy.

Figure 1

Use of quantum dots (QDs) and related nanoparticles for direct visualization of tumors during surgery. Shown here are two color images of a pig lung obtained with (a) bright-field visible illumination and (b) near-UV illumination. Note that the fluorescence image shows a bright spot (orange) that corresponds to injected QDs.

Figure 2

Schematic diagram showing nanoparticle accumulation in solid tumors through both active and passive targeting mechanisms. In the passive mode, nanometer-sized particles such as SERS nanoparticles and quantum dots accumulate at tumor sites through an enhanced permeability and retention (EPR) effect (–27). For active tumor targeting, nanoparticles are conjugated to molecular ligands, such as antibodies and peptides, to recognize protein targets that are overexpressed on the surface of tumor cells, such as the epidermal growth factor receptor (EGFR), the transferrin receptor, or the folate receptor. (Courtesy of X. Qian and S. Nie, Emory University, Atlanta, GA; adapted for publication by Annual Reviews.)

Figure 3

In vivo cancer targeting and surface-enhanced Raman scattering (SERS) detection by using ScFv-antibody conjugated gold nanoparticles that recognize the tumor biomarker EGFR. Photographs show a laser beam focusing on (a) the tumor site or (b) the anatomical location of liver. SERS spectra were obtained from the tumor and liver locations by using (a) targeted and (b) nontargeted nanoparticles. Two nude mice bearing human head and neck squamous cell carcinoma (Tu686) xenograft tumor (3 mm diameter) received 90 μL of ScFv EGFR-conjugated SERS tags or pegylated SERS tags. Adapted with permission from Reference 28.