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Nowadays, one of the most exciting applications of nanotechnology in biomedicine is the development of localized, noninvasive therapies for diverse diseases, such as cancer. Among them, nanoparticle-based photothermal therapy (PTT), which destroys malignant cells by delivering heat upon optical excitation of nanoprobes injected into a living specimen, is emerging with great potential. Two main milestones that must be reached for PTT to become a viable clinical treatment are deep penetration of the triggering optical excitation and real-time accurate temperature monitoring of the ongoing therapy, which constitutes a critical factor to minimize collateral damage. In this work, a yet unexplored capability of near-infrared emitting semiconductor nanocrystals (quantum dots, QDs) is demonstrated. Temperature self-monitored ­QD-based PTT is presented for the first time using PbS/CdS/ZnS QDs emitting in the second biological window. These QDs are capable of acting, simultaneously, as photothermal agents (heaters) and high-resolution fluorescent thermal sensors, making it possible to achieve full control over the intratumoral temperature increment during PTT. The differences observed between intratumoral and surface temperatures in this comprehensive investigation, through different irradiation conditions, highlight the need for real-time control of the intratumoral temperature that allows for a dynamic adjustment of the treatment conditions in order to maximize the efficacy of the therapy., This project was supported by the Spanish Ministerio de Economía y Competitividad under project and MAT2013-47395-C4-1-R. B.d.R. thanks Universidad Autónoma de Madrid for an FPI grant. F.R. acknowledges scholarship support from the Fonds de recherche du Québec—Nature et technologies (FRQNT) under the Programme de Bourses d’Excellence (Merit Scholarship Program for Foreign Students). A.B. is thankful to the Canadian Institutes of Health Research and the Breast Cancer Society of Canada (CIHR-BCSC), for postdoctoral funding granted to him through an Eileen Iwanicki Fellowship in Breast Cancer Imaging. F.V. is grateful to the Natural Sciences and Engineering Research Council (NSERC) of Canada, FRQNT, and the Canada Foundation for Innovation (CFI) for supporting his research program. F.V. also gratefully acknowledges the Fondation Sibylla Hesse. D.M. is grateful for the financial support from NSERC, FRQNT, CFI, and the Centre Québécois sur les Matériaux Fonctionnels (CQMF), Canada

Over the past decade, near-infrared (NIR)-emitting nanoparticles have increasingly been investigated in biomedical research for use as fluorescent imaging probes. Here, high-quality water-dispersible core/shell/shell PbS/CdS/ZnS quantum dots (hereafter QDs) as NIR imaging probes fabricated through a rapid, cost-effective microwave-assisted cation exchange procedure are reported. These QDs have proven to be water dispersible, stable, and are expected to be nontoxic, resulting from the growth of an outer ZnS shell and the simultaneous surface functionalization with mercaptopropionic acid ligands. Care is taken to design the emission wavelength of the QDs probe lying within the second biological window (1000-1350 nm), which leads to higher penetration depths because of the low extinction coefficient of biological tissues in this spectral range. Furthermore, their intense fluorescence emission enables to follow the real-time evolution of QD biodistribution among different organs of living mice, after low-dose intravenous administration. In this paper, QD platform has proven to be capable (ex vivo and in vitro) of high-resolution thermal sensing in the physiological temperature range. The investigation, together with the lack of noticeable toxicity from these PbS/CdS/ZnS QDs after preliminary studies, paves the way for their use as outstanding multifunctional probes both for in vitro and in vivo applications in biomedicine. Low-dose in vivo near-infrared (NIR) fluorescence imaging is achieved by using carefully designed PbS/CdS/ZnS quantum dots (QDs), intensely emitting within the second biological window (1000-1350 nm). Moreover, preliminary studies both in vitro and in vivo have proven the lack of noticeable toxicity of these QDs. As an additional advantage, this NIR-fluorescence imaging platform has demonstrated useful multifunctionality, thus being capable, both ex vivo and in vitro, of high-resolution thermal sensing in the physiological temperature range., A.B., F.R., and E.C. contributed equally to this work. A.B. thanks the Fonds de recherche du Québec-Nature et Technologies (FRQNT) and the Canadian Institutes of Health Research–Breast Cancer Society of Canada (CIHR-BCSC) for postdoctoral funding through the Programme de Bourses d’Excellence and an Eileen Iwanicki Fellowship in Breast Cancer Imaging, respectively. F.R. greatly appreciates financial support from the Merit Scholarship Program for Foreign Students from the Ministére de L’Education, du Loisir et du Sport du Québec (MELS). F.V. and D.M. are grateful to the Natural Sciences and Engineering Research Council of Canada (NSERC) and FRQNT for funding. F.V. wholeheartedly thanks the Foundation Sibylla Hesse for supporting his research. D.M. also thanks the Quebec Center for Functional Materials for support. This work was also supported by Spanish Ministerio de Economia y Competitividad under projects MAT2010–16161 and MAT2013–47395-C4–1-R.