Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma

TLDR

Nanoparticle-based materials in oncology trials largely lack tumor selectivity, and developing probes that are selective, nontoxic, and clear efficiently requires comprehensive in vivo evaluation. The study characterizes a ~7‑nm multimodal silica nanoparticle designed to be tumor‑selective, nontoxic, and to clear efficiently. The nanoparticle consists of a ~7‑nm silica core loaded with dye, surface‑functionalized with cyclic RGD peptide and radioiodine, enabling high‑affinity binding to αvβ3 integrin and rapid renal clearance. Approved for a first‑in‑human trial, the particle achieved rapid renal clearance, selective tumor accumulation, high‑affinity binding to αvβ3 integrin, and enabled real‑time imaging of lymphatic drainage, metastases, and tumor burden in a large‑animal melanoma model, highlighting its potential for clinical staging of metastatic disease.

Abstract

Nanoparticle-based materials, such as drug delivery vehicles and diagnostic probes, currently under evaluation in oncology clinical trials are largely not tumor selective. To be clinically successful, the next generation of nanoparticle agents should be tumor selective, nontoxic, and exhibit favorable targeting and clearance profiles. Developing probes meeting these criteria is challenging, requiring comprehensive in vivo evaluations. Here, we describe our full characterization of an approximately 7-nm diameter multimodal silica nanoparticle, exhibiting what we believe to be a unique combination of structural, optical, and biological properties. This ultrasmall cancer-selective silica particle was recently approved for a first-in-human clinical trial. Optimized for efficient renal clearance, it concurrently achieved specific tumor targeting. Dye-encapsulating particles, surface functionalized with cyclic arginine-glycine-aspartic acid peptide ligands and radioiodine, exhibited high-affinity/avidity binding, favorable tumor-to-blood residence time ratios, and enhanced tumor-selective accumulation in αvβ3 integrin-expressing melanoma xenografts in mice. Further, the sensitive, real-time detection and imaging of lymphatic drainage patterns, particle clearance rates, nodal metastases, and differential tumor burden in a large-animal model of melanoma highlighted the distinct potential advantage of this multimodal platform for staging metastatic disease in the clinical setting.