A Novel Clinically Translatable Fluorescent Nanoparticle for Targeted Molecular Imaging of Tumors in Living Subjects

• Published in: Nano letters Vol. 12; no. 1; pp. 281 - 286
• Main Authors: Gao, Jinhao, Chen, Kai, Luong, Richard, Bouley, Donna M, Mao, Hua, Qiao, Tiecheng, Gambhir, Sanjiv S, Cheng, Zhen
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 11.01.2012
• Subjects: Animals; Applied sciences; Biocompatibility; Cross-disciplinary physics: materials science; rheology; Electronics; Exact sciences and technology; General equipment and techniques; Imaging; Instruments, apparatus, components and techniques common to several branches of physics and astronomy; Materials science; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence - methods; Molecular electronics, nanoelectronics; Molecular Imaging - methods; Nanocrystalline materials; Nanoscale materials and structures: fabrication and characterization; Nanostructure; Neoplasms, Experimental - pathology; Physics; Quantum Dots; Semiconductor electronics. Microelectronics. Optoelectronics. Solid state devices; Sensors (chemical, optical, electrical, movement, gas, etc.); remote sensing; Stability; Surgical implants; Toxicity; Tumors; Uptakes; Whole Body Imaging - methods; renal clearance; clinical translation; Nanoprobes; molecular imaging; fluorescence; Doses; Tumor cells; Quantum dots; Size stability; Core shell structure; Toxicity; Infrared spectra; III-V compound; Indium phosphide; Nanoparticles; Near infrared radiation; Zinc sulfide; In vivo; Fluorescent material; II-VI semiconductors; Near infrared spectrum; Tumours; Imaging; Biocompatibility; Nanostructured materials; Nanoprobe; III-V semiconductors
• DOI: 10.1021/nl203526f
• ISSN: 1530-6984; 1530-6992

The use of quantum dots (QDs) in biomedical research has grown tremendously, yet successful examples of clinical applications are absent due to many clinical concerns. Here, we report on a new type of stable and biocompatible dendron-coated InP/ZnS core/shell QD as a clinically translatable nanoprobe for molecular imaging applications. The QDs (QD710-Dendron) were demonstrated to hold several significant features: near-infrared (NIR) emission, high stability in biological media, suitable size with possible renal clearance, and ability of extravasation. More importantly, a pilot mouse toxicity study confirmed that QD710-Dendron lacks significant toxicity at the doses tested. The acute tumor uptake of QD710-Dendron resulted in good contrast from the surrounding nontumorous tissues, indicating the possibility of passive targeting of the QDs. The highly specific targeting of QD710-Dendron-RGD2 to integrin αvβ3-positive tumor cells resulted in high tumor uptake and long retention of the nanoprobe at tumor sites. In summary, QD710-Dendron and RGD-modified nanoparticles demonstrate small size, high stability, biocompatibility, favorable in vivo pharmacokinetics, and successful tumor imaging properties. These features satisfy the requirements for clinical translation and should promote efforts to further investigate the possibility of using QD710-Dendron-based nanoprobes in the clinical setting in the near future.