Effects of arginine–glycine–aspartic acid peptide-conjugated quantum dots-induced photodynamic therapy on pancreatic carcinoma in vivo

Abstract

Ming-Ming Li,* Jia Cao,* Jia-Chun Yang, Yu-Jie Shen, Xiao-Lei Cai, Yuan-Wen Chen, Chun-Ying Qu, Yi Zhang, Feng Shen, Lei-Ming Xu Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Quantum dots (QDs) conjugated with integrin antagonist arginine–glycine–aspartic acid (RGD) peptides (QDs-RGD) are novel nanomaterials with a unique optical property: a high molar extinction coefficient. Previously, we have shown that QDs-RGD demonstrate a photodynamic therapy (PDT) effect as new photosensitizers for the pancreatic cancer cell line SW1990 in vitro. Here, we investigate the application of QDs-RGD in mice bearing pancreatic tumors using PDT. To ensure that more photosensitizers accumulated in tumors, QDs-RGD were injected intratumorally. After selection of an adequate dosage for injection from analyses of biodistribution images captured by an IVIS system, PDT was initiated. Three groups were created according to different PDT procedures. In group 1, mice were injected with QDs-RGD intratumorally, and an optical fiber connected to a laser light was inserted directly into the tumor. Irradiation was sustained for 20 min with a laser light (630 nm) at 100 mW/cm2. In group 2, the laser optical fiber was placed around, and not inserted into, tumors. In group 3, PDT was conducted as in group 1 but without injection of QDs-RGD. After 28 days of observation, tumors on the back of mice in group 1 grew slowly (V/V0 =3.24±0.70) compared with the control groups, whose tumors grew quickly, and the mean V/V0 reached 6.08±0.50 (group 2) and 7.25±0.82 (group 3). Histology of tumor tissues showed more necrotic tissues, more inflammatory cells, and less vascular tissue in the PDT group than those in the control groups. These results suggest that QDs-RGD-mediated PDT, with illumination using an optical fiber inserted directly into the tumor, can inhibit the growth of SW1990 tumors with high efficiency in nude mice. Keywords: quantum dots, RGD peptides, pancreatic neoplasm, intratumoral injection, photodynamic therapy

Keywords

• quantum dots
• RGD peptides
• pancreatic neoplasm
• intratumoral injection
• photodynamic therapy