Intratumoral Thermal Reading During Photo‐Thermal Therapy by Multifunctional Fluorescent Nanoparticles

Abstract

The tremendous development of nanotechnology is bringing us closer to the dream of clinical application of nanoparticles in photothermal therapies of tumors. This requires the use of specifi c nanoparticles that must be highly biocompatible, effi cient light-to-heat converters and fl uorescent markers. Temperature reading by the heating nanoparticles during therapy appears of paramount importance to keep at a minimum the collateral damage that could arise from undesirable excessive heating. In this work, this thermally controlled therapy is possible by using Nd 3+ ion-doped LaF 3 nanocrystals. Because of the particular optical features of Nd 3+ ions at high doping concentrations, these nanoparticles are capable of in vivo photothermal heating, fl uorescent tumor localization and intratumoral thermal sensing. The successful photothermal therapy experiments here presented highlight the importance of controlling therapy parameters based on intratumoral temperature measurements instead of on the traditionally used skin temperature measurements. In fact, signifi cant differences between intratumoral and skin temperatures do exist and could lead to the appearance of excessive collateral damage. These results open a new avenue for the real application of nanoparticle-based photothermal therapy at clinical level.

Neodymium‐Based Stoichiometric Ultrasmall Nanoparticles for Multifunctional Deep‐Tissue Photothermal Therapy

“…As can be observed, the absorption of our NdVO4 NPs is markedly larger than that of the heavily-doped Nd:LaF3 NPs that have been successfully used as photothermal agents. [16] From the absorption spectrum included in Figure 1(c) we have estimated a peak absorption cross section per NP mass close to 75 cm 2 ·g -1 for the NdVO4 stoichiometric NPs. This is, roughly, 20 times that estimated for the previously used Nd:LaF3 PT-NPs (close to 3.8 cm 2 ·g -1 for a neodymium concentration of 5.6 at.%) that cannot be solely explained by the different neodymium concentration (about 4 times higher in NdVO4 stoichiometric NPs than in Nd:LaF3 NPs).…”

“…[15a, 16] It is important to note that the heating efficiency of Nd:LaF3 NPs would be about 80% higher if the excitation wavelength matched the absorption peak (≈ 789 nm). [16] However, even after wavelength optimization, the heating efficiency of Nd:LaF3 would still be lower than that of NdVO4 NPs. This could be explained in terms of the larger absorption cross section of the NdVO4 NPs, as has been previously discussed, and also in terms of a larger the fractional thermal loading (fraction of the absorbed energy that is converted into heat) of NdVO4 NPs, which is known to increase with neodymium concentration in a nonlinear way.…”

“…This could be explained in terms of the larger absorption cross section of the NdVO4 NPs, as has been previously discussed, and also in terms of a larger the fractional thermal loading (fraction of the absorbed energy that is converted into heat) of NdVO4 NPs, which is known to increase with neodymium concentration in a nonlinear way. [16] At this point, we should note that the fact that the optimum excitation wavelength of NdVO4 NPs is 808 nm instead of 790 nm is an additional advantage, as 790 nm radiation has been demonstrated to be much more harmful to cells than 808 nm radiation. [12] The superior heating efficiency of ultrasmall NdVO4 stoichiometric NPs indicates that using them as photothermal agents for tumor treatments would substantially reduce the optical excitation densities required for efficient treatment when compared to previously used neodymium-doped PT-NPs.…”

“…[15] In particular, heavily-doped (5.6 at.%) Nd:LaF3 NPs have been successfully used for self-monitored temperature controlled photothermal therapy. [16] Previous studies have concluded that, while Nd:NPs display the already mentioned interesting properties (such as superior spectral and physical stabilities), they also present the disadvantage of a relatively low absorption cross section per NP, which results in a nonefficient absorption of optical excitation radiation. [3] Such reduced absorption cross section stems from the intrinsic low absorption probabilities characteristic of Nd 3+ ions as well as from the typically low content of Nd 3+ ions per RENP (usually below 10 mol.%).…”

Infrared‐Emitting QDs for Thermal Therapy with Real‐Time Subcutaneous Temperature Feedback

“…Each bar corresponds to the mean cell viability value ± standard deviation. [31] Graphene NPs 808 5 0.15 48 38 [32] GNRs 810 3 2 75 40 [33] Sb NPs 808 5 1 55 37 [34] FeS nanoplates 808 5 1 60 45 [35] LaF3:Nd 808 4 4 48 41 [36] MoS2-iron oxide 808 5 0.78 51 40 [37] Mn-iron oxide 808 5 1.5 70 43 [38] WS2 QDs 808 10 1 ~45 38 [30] Table S3. Treatment conditions (irradiation wavelength, duration and power density) and surface maximum temperatures for different PTT experiments in animal models.…”