Layer-by-layer assembled fluorescent probes in the second near-infrared window for systemic delivery and detection of ovarian cancer.
Fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) features deep tissue penetration, reduced tissue scattering, and diminishing tissue autofluorescence. Here, NIR-II fluorescent probes, including down-conversion nanoparticles, quantum dots, single-walled carbon nanotubes, and organic dyes, are constructed into biocompatible nanoparticles using the layer-by-layer (LbL) platform due to its modular and versatile nature. The LbL platform has previously been demonstrated to enable incorporation of diagnostic agents, drugs, and nucleic acids such as siRNA while providing enhanced blood plasma half-life and tumor targeting. This work carries out head-to-head comparisons of currently available NIR-II probes with identical LbL coatings with regard to their biodistribution, pharmacokinetics, and toxicities. Overall, rare-earth-based down-conversion nanoparticles demonstrate optimal biological and optical performance and are evaluated as a diagnostic probe for high-grade serous ovarian cancer, typically diagnosed at late stage. Successful detection of orthotopic ovarian tumors is achieved by in vivo NIR-II imaging and confirmed by ex vivo microscopic imaging. Collectively, these results indicate that LbL-based NIR-II probes can serve as a promising theranostic platform to effectively and noninvasively monitor the progression and treatment of serous ovarian cancer.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Xiangnan
X
Dang
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Li
L
Gu
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Jifa
J
Qi
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Santiago
S
Correa
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
Geran
G
Zhang
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 belcher@mit.edu hammond@mit.edu.
Angela M
AM
Belcher
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; belcher@mit.edu hammond@mit.edu.
Paula T
PT
Hammond
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D003460:Crystallization / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D000068936:Theranostic Nanomedicine / Q000379:methods; D014018:Tissue Distribution
D003287:Contrast Media; D005456:Fluorescent Dyes; D053769:Nanocapsules
deep penetration; layer by layer; ovarian tumor detection; second near-infrared window; systemic comparison