Rational design of multimodal and multifunctional InP quantum dot nanoprobes for cancer: in vitro and in vivo applications

Abstract

In this paper we report the development of multifunctional nanoprobes based on InP–ZnS quantum dots (QDs) for high contrast multimodal imaging and other applications for cancer in vitro and in vivo. These theranostic nanoprobes were synthesized by co-encapsulating InP–ZnS QDs and anticancer drug molecules within PEGylated phospholipid micelles covalently linked with DOTA-chelated Gd³⁺. Luminescent biocompatible InP–ZnS QDs and Gd³⁺ chelates can be used for fluorescence microscopy and magnetic resonance imaging (MRI), respectively. The nanoprobes showed both optical and MRI capabilities. The therapeutic effect of the theranostic nanoprobes was evaluated using cell viability assays and the toxic effect of the released anticancer drugs from the probes was confirmed on the cancer cells. For targeted delivery in vitro, the micelle-encapsulated QDs were conjugated with transferrin and anti-claudin-4 antibody, which target the transferrin- and claudin-4-receptors overexpressed in cancer cells, respectively. Employing in vivo optical imaging of mice bearing pancreatic cancer xenografts, we have demonstrated that systemically-delivered anti-claudin-4 conjugated QD nanoprobes can target and label the tumors with high contrast. These studies suggest that the developed theranostic InP–ZnS QD nanoprobes have the potential to be translated in clinical research for targeted multimodal diagnosis and therapy of cancer.