Engineering the Infrared Luminescence and Photothermal Properties of Double-Shelled Rare-Earth-Doped Nanoparticles for Biomedical Applications

Abstract

The nascent field of theranostics, which couples targeted therapy with diagnostics, has catalyzed efforts toward improved nanoprobe designs that facilitate both localized treatment and diagnostic imaging. Rare-earthdoped nanoparticles (RENPs) have emerged as a leading candidate for theranostics because of their versatile synthesis and modification chemistries, photostability, and relative safety. Furthermore, their bright, tunable fluorescence using near-infrared (NIR) excitation enables multispectral imaging with high signal-to-background ratios. In this work, we have synthesized double-shelled RENPs with tunable properties for optimal fluorescent imaging, photoacoustic imaging, and photothermal therapy. The properties of the double-shelled RENPs were tailored by controlling the density of rare-earth ions (i.e., activator or sensitizer) by using either a functional amorphous organic or a crystalline outermost shell. This study systematically analyzes the effects of the functional organic or inorganic outermost shell on the imaging and photothermal conversion properties of our RENPs. Despite the weaker infrared absorption enhancement, the functional organic outermost shell impregnated with a low density of rare-earth ions led to minimal reduction of fluorescence emissions. In contrast, the higher density of rare-earth ions in the inorganic shell led to higher infrared absorption and consequently significant reduction in emissions arising from the undesired optical attenuation. Inorganic shell thickness was therefore modified to reduce the deleterious attenuation, leading to brighter emissions that also enabled the in vitro SWIR detection of ∼2500 cells/cluster. Using the enhanced infrared properties that arise from this functional inorganic layer, which could be engineered to respond to either NIR or SWIR, we demonstrated that (1) bright SWIR emissions allowed detection of small cell clusters; (2) strong PA signals allowed clear visualization of particle distribution within tumors; and (3) strong photothermal effects resulted in localized elevated temperatures. Collectively, these results highlight the utility of these double-shelled RENPs as theranostic agents that are compatible with both photoacoustic or fluorescent imaging platforms.

Biodegradable rare earth fluorochloride nanocrystals for phototheranostics

“…The rapid in vivo clearance was most likely facilitated by the degradation of SrFCl:Nd 2 in the aqueous environment. Compared to our previous studies where particle clearance from the tumor site was typically observed between 2 to 3 days using much smaller uoride nanocrystals, 5,6,19 the much faster clearance of the much larger SrFCl:Nd 2 @PDA within 12 h post injection suggests that the solubilization of SrFCl was instrumental towards the rapid inorganic nanocrystal clearance. The strong PA signal aer intravenous injection coupled with complete clearance at 6 h aer injection shows that SrFCl:Nd 2 @PDA NPs is a suitable PA imaging diagnostic agent.…”

“…Inorganic nanoparticles are widely investigated for therapeutic and diagnostic purposes in both preclinical and clinical phases as they offer numerous unique size-dependent physicochemical, magnetic (e.g., superparamagnetic contrast agents) and optical properties (e.g., quantum dots). [1][2][3][4][5][6] However, there are few instances where inorganic nanomaterials have been used in clinical applications. Unlike their organic or polymeric counterparts, the poor solubility of inorganic crystalline nanomaterials precludes their efficient clearance from the body.…”

Proceedings of the SOLAR 20/20 Conference

“…The photothermal (PT) effect has been investigated for biomedical applications in the past two decades, such as the studies on sensing, imaging, therapies, and drug deliveries. 5,6 The PT effect includes two stages, the photonic energy absorption, and photon-induced heat generation. The first stage usually happens in the way of absorption and may exist in other photonic extinction due to the microstructure of the material, such as multiple scattering.…”

“…While the paper discusses the 22 specs for a model HSP, there is also no case study to discuss how to compile 6 the 22 HSP base case specs from the current authoritative data sources. Readers who want learn how to compile 6 Putting the paper's LCOS algorithm in an Excel Workbook allows the reader (author, banker, engineer) to quickly do sensitivity analysis. For the reader to follow this paper, the reader must download this paper's Excel HSP LCOS Financial Algorithm Workbook from this paper's Additional Material Section 7 at SOLAR 20/20 Conference Proceedings Website: [Link].…”

“…In the base case, the HE spec values, WS # 1, Lines 4,6,7,8 & 9, have also been used as the H2 "Tank" spec values, WS # 2, Lines 11,12,13,14 & 15,and as the FC spec values WS # 3,Lines 18,19,20,21 & 22 11 . A specific example is WS # 1, Line 9, Cost of Capital, interest rate/ROE [WACC] is set at 6%, which is the author's base case estimate.…”