Assessing Clinical Prospects of Silicon Quantum Dots: Studies in Mice and Monkeys

Abstract

Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots.

Direct band gap silicon quantum dots achieved via electronegative capping

“…Size-tunable optical band gap allows for emission spectrally tunable in wide UV-to-IR regions (260-1100 nm), attractive for the currently developing market of QD-based light-emitting diodes and displays [4][5][6]. Nontoxicity [7][8][9], biodegradability [10], and superior photo-and pH stability [11] of SiQDs open opportunities in traditionally high health risk areas such as medicine or cosmetics. However, even though quantum confinement in SiQDs leads to considerable improvement in radiative rates, their magnitude remains still very low (e.g., 10 4 s −1 for small ∼ 2.5 nm H-capped SiQD), compared to direct band gap semiconductors utilized for light emitter and laser applications (of the order of 10 7 -10 9 s −1 ).…”

Optical Biosensing and Bioimaging With Porous Silicon and Silicon Quantum Dots (Invited Review)

“…At the new frontiers of nanostructure silicon research, biomedical applications are very appealing because silicon is highly biocompatible [4]. With the small sized silicon materials suitable for these applications, two distinct structures are porous silicon, and silicon nanocrystals which are also called quantum dots.…”

Cationic Silicon Nanocrystals with Colloidal Stability, pH‐Independent Positive Surface Charge and Size Tunable Photoluminescence in the Near‐Infrared to Red Spectral Range

“…In particular, the toxicity of heavy‐metal‐based nanocrystals has been subject to intense scrutiny 4, 5, 6, 7. In recent years, silicon nanocrystals (ncSi) have been proposed and demonstrated as potentially nontoxic alternatives to established II–VI (e.g., CdSe/Te, ZnS/Se), III–V (e.g., InP), I–III–VI (e.g., CuInS/Se), and IV–VI (e.g., PbS/Se) nanocrystal systems for fluorescent labeling 4, 8, 9, 10…”