Gastric cancer has ranked as one of the most frequent tumors in the world with approximately 989,000 new cases and 738,000 deaths per year . The most important part in surgery is to correctly define the boundary of the tumor and precisely determine the regions for surgical resection in order to improve survival rate and quality of life. However, visualized methods to detect the tumor cells during surgery are currently not available. Both D1 lymphadenectomy proposed by Western researchers and D2 lymphadenectomy proposed by Japanese researchers cannot achieve high specificity . Clinical doctors could only estimate the tumor boundary for surgical resection by experience and the changes of the tumor tissue texture, which results in a high failure rate of complete removal of gastric cancer and greatly affects the survival rate of the patients. Therefore, development of methods for real-time identification of tumor cells and metastasized lymph nodes during surgery and establishment of tailored surgical resection for each individual are one of the key factors in improving the survival rate for gastric cancer.
Recently, quantum dots (QDs) were developed on the interdisciplinary advancement of nanotechnology, chemistry, and optics. The unique optical properties of QDs have shown promising prospects in the tumor tissue and metastasized lymph node clearance for cancer patients . Compared with traditional organic dyes, inorganic semiconductor QDs exhibit more advantages on light absorption, bright fluorescence, narrow symmetric emission bands, high photostability, and size-tunable optical properties and are considered to be valuable fluorescent probes for tissue imaging. Particularly, people pay close attention to near-infrared (NIR) QDs for visible in vivo tissue imaging due to their reduced absorbance and scattering in biological tissues within the NIR region, as well as the strong penetration in human tissues. The unique optical properties and the ease of modification of QDs by some bioactive materials make these nanoparticles as highly promising fluorescent labels for in vivo biological applications [4, 5]. Currently, fluorescent probes have been developed by conjugating QDs with target molecules (e.g., antibodies and peptides) and have been used for in vivo visualization of cancer cells , sentinel lymph node detection [7, 8], and imaging of drug targeting studies . More important, new synthetic techniques of QDs biologically functionalized QDs with excellent biological compatibility and water solubility, which pave the way for the application of tissue imaging in vivo.
A common limitation of the QDs’ use in tissue imaging in vivo was their potential toxicity. Some researchers claimed that the oxidation of Cd2+ on the QD surface and subsequent Cd2+ release may induce potential cytotoxicity . However, many authoritative studies showed that there was no significant influence on cell viability, morphology, function, or development in the use of QDs [12, 13]. Besides, no obvious toxicity evidence was obtained during in vivo imaging [7, 14–16]. In our previous experiments, CdTe quantum dots were proved not having acute toxicity to rats when they were injected in the subserosa layer of the rats’ stomach .
Many studies have demonstrated that 75% of gastric adenocarcinomas highly express tumor-associated glycoprotein 72 (TAG-72) . Specific targeting of TAG-72 by CC49 antibodies has been widely used for the treatment of gastric cancer [19–21]. Therefore, visual imaging by targeting TAG-72 has broad applicability for gastric cancer detection. The authors of this research attached CC49 monoclonal antibodies to QDs with a maximal emission wavelength of 710 nm to produce a probe designated as CC49-QDs and reported the use of CC49-QDs as fluorescent probes for imaging the human gastric adenocarcinoma cell line MGC80-3.