In Vivo Early Tumor Detection and Diagnosis by Infrared Luminescence Transient Nanothermometry

Abstract

The development of technologies capable of early tumor detection is unquestionably demanded by physicians, as early diagnosis is key to achieve more efficient and less invasive treatments with improved outcomes. At the preclinical level, nanotechnology has already provided innovative solutions for tumor imaging and therapy, but it has failed to provide real early tumor diagnosis. In this work, an infrared nanothermometry-based approach toward early melanoma detection, based on the changes produced in the thermal relaxation dynamics of tissues as the tumor develops, is introduced. In vivo experiments demonstrate that detection of incipient tumors from their very onset is possible through monitoring changes in their thermal relaxation dynamics using Ag 2 S infrared luminescent nanothermometers. For a total tumor development time of 14 days, luminescence nanothermometry allows tumor detection 6 days before its presence is evident by visual inspection. Simultaneous study of the tumoral vasculature reveals that the premature variation in the thermal relaxation dynamics is a consequence of the interplay between tumor angiogenesis and necrosis during the different tumor development stages.

Lanthanide‐Based Thermometers: At the Cutting‐Edge of Luminescence Thermometry

“…Without using Ln 3+ ions, Santos et al use the temporal decay temperature profiles monitored by Ag 2 S IR nanothermometers to early‐tumor diagnosis. Changes in tissues are discerned through changes in their thermal dynamics measured by thermal transient thermometry.…”

“…The background colors and vertical lines indicate the time when the tumor becomes detectable by the different methods. Adapted with permission . Copyright 2018, Wiley‐VCH.…”

“…In the former case, examples include recording of in vivo thermal images, acquisition of subcutaneous thermal videos, and in vivo ischemia recognition in small animals . Early tumor detection becomes possible by transient thermometry using near‐infrared (NIR) emitting Ag 2 S nanocrystals . Examples of the later approach are the analysis of heat flux assessment in heater‐thermometer nanoplatforms, the estimation of the absorption coefficient and of the thermal diffusivity of tissues, the quantification of the instantaneous ballistic velocity of Brownian nanocrystals suspended in aqueous and organic solvents, the determination of the thermal conductivity of porous silica and titania nanostructures, and the measurement of the thermal resistance of NPs (in air) .…”

“…Among these recent examples, the present manuscript considers essentially those based on Ln 3+ ions, being a follow up of the two books and the review papers published since 2015 on Ln 3+ ‐based luminescent thermometers . The few examples involving other emitting centers are included in the text either in the context of historical reasons, e.g., the ZnCdS‐based phosphors, or due to its enormous impact for the development of the area, e.g., the Ag 2 S nanocrystals …”

Ratiometric upconversion nanothermometry with dual emission at the same wavelength decoded via a time-resolved technique

“…L uminescent nanothermometry has attracted considerable interest as a novel type of sub-micrometric thermal reading due to its strong temperature-dependent luminescence in nanosize [1][2][3][4][5] . Benefitting greatly from its high resolution, high sensitivity, and noninvasiveness, it is widely applied in biology [6][7][8][9][10] , thermodynamics [11][12][13][14][15][16] , and nanomedicine [17][18][19][20][21] . Luminescent thermal reading can provide temperature measurements in inflamed regions in vivo via contactless and noninvasive luminescence bioimaging 22,23 .…”