Intraoperative mapping of sentinel lymph node metastases using a clinically translated ultrasmall silica nanoparticle

Abstract

The management of regional lymph nodes in patients with melanoma has undergone a significant paradigm shift over the past several decades, transitioning from the use of more aggressive surgical approaches, such as lymph node basin dissection, to the application of minimally invasive sentinel lymph node (SLN) biopsy methods to detect the presence of nodal micrometastases. SLN biopsy has enabled reliable, highly accurate, and low-morbidity staging of regional lymph nodes in early stage melanoma as a means of guiding treatment decisions and improving patient outcomes. The accurate identification and staging of lymph nodes by imaging is an important prognostic factor, identifying those patients for whom the expected benefits of nodal resection outweigh attendant surgical risks. However, currently used standard-of-care technologies for SLN detection are associated with significant limitations. This has fueled the development of clinically promising platforms that can serve as intraoperative visualization tools to aid accurate and specific determination of tumor-bearing lymph nodes, map cancer-promoting biological properties at the cellular/molecular levels, and delineate nodes from adjacent critical structures. Among a number of promising cancer-imaging probes that might facilitate achievement of these ends is a first-in-kind ultrasmall tumor-targeting inorganic (silica) nanoparticle, designed to overcome translational challenges. The rationale driving these considerations and the application of this platform as an intraoperative treatment tool for guiding resection of cancerous lymph nodes is discussed and presented within the context of alternative imaging technologies.

Colloidal capsules: nano- and microcapsules with colloidal particle shells

“…A great number of the above described colloidal capsules are developed to be used in bionanotechnology, like biosensing, bioimaging or targeted drug delivery. With silica [314][315][316][317] (e.g. CÁspec s ), quantum dots 318,319 (e.g.…”

Target-or-Clear Zirconium-89 Labeled Silica Nanoparticles for Enhanced Cancer-Directed Uptake in Melanoma: A Comparison of Radiolabeling Strategies

“…At present, and to the best of our knowledge, ultrasmall dye-encapsulating, α v β 3 integrin-targeting cyclic(arginine-glycine-aspartic acid-D-tyrosine-cysteine) (cRGDY) peptide carrying and PEG-functionalized fluorescent core–shell silica nano-particles (also known as Cornell dots or cRGDY-PEG-C dots) are congruent with the foregoing description of highly desirable characteristics that are achievable for such nanoscale materials. 16,17,19,20 Next-generation Cornell prime dots synthesized in water-based environments, 21 cRGDY-PEG-C′ dots, are currently being utilized to study modulations in biological responses 22 and as an iodine-124- ( 124 I, t 1/2 = 100.2 h) labeled, PET-optical platform for preclinical oncological indications 23,24 and early phase clinical trials (NCT01266096 and NCT02106598).…”

Nanoparticles and radiotracers: advances toward radionanomedicine

“…A more in depth coverage of SLN mapping with ultra small SNPs can be found in this review. 74 For longer imaging studies, 111 In, 67 Ga, and various iodine species are used. 67 Ga (t 1/2 = 2.2d) and 111 In (t 1/2 = 2.8d) have been used to radiolabel NP via both chelator-free methods 40,41 as well as a diethylenetriamine-pentaacetic acid (DTPA) chelator.…”