Molecular phenotyping and image-guided surgical treatment of melanoma using spectrally distinct ultrasmall core-shell silica nanoparticles

Abstract

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

Use of Ultrasmall Core-Shell Fluorescent Silica Nanoparticles for Image-Guided Sentinel Lymph Node Biopsy in Head and Neck Melanoma

“…were found to be strongly correlated with nodal tumor burden. 46 The results of our pilot study show that the use of cRGDY-PEG-Cy5 A primary end point of the study rested on the need for accurate intraoperative detection of SLNs identified on preoperative 99m Tc lymphoscintigraphy. High concordance (90%) was found between the proportion of ex vivo SLNs identified by technetium Tc 99m sulfur colloid and that optically visualized by cRGDY-PEG-Cy5.5-nanoparticles following early optimization procedures.…”

Ultrasmall, Bright, and Photostable Fluorescent Core–Shell Aluminosilicate Nanoparticles for Live‐Cell Optical Super‐Resolution Microscopy

“…Optical SRM with aC' dots will therefore enable the direct study, in particular, of intracellular particle processing details in live cells relevant to questions associated with the clinical translation of diagnostic as well as therapeutic C' dot applications. [27,[62][63][64][65]…”

Molecular Engineering of Ultrasmall Silica Nanoparticle–Drug Conjugates as Lung Cancer Therapeutics

“…[36][37][38], as a drug delivery vehicle offering improved therapeutic properties over the corresponding native drug in a patientderived model of NSCLC. Our prior work has shown that dyeencapsulated C 0 dots can be surface modified with an array of functional groups (37)(38)(39)(40)(41)(42)(43) and radiotracers (40,44) for mapping disease in both surgical (45) and nonsurgical settings (39,41), as well as for investigating biological properties and targeted inhibition in a high-grade glioma model (46). In addition, we have demonstrated the successful conjugation and in vitro therapeutic activity of a protease-sensitive gefitiniblinker construct to an earlier generation silica nanoparticle, which was found to inhibit EGFR signaling in vitro (47).…”