Научная статья на тему 'Nanophotonic detection of tumor markers and micrometastases with conjugates of single-domaine antibodies and quantum dots'

Nanophotonic detection of tumor markers and micrometastases with conjugates of single-domaine antibodies and quantum dots Текст научной статьи по специальности «Физика»

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Аннотация научной статьи по физике, автор научной работы — Igor Nabiev

To improve cancer prognosis, early detection of the disease is one of the main purposes in diag-nostic approaches. In this regard, the rapidly progressing field of nanotechnology is considered a power-ful tool in cancer diagnostic and therapeutic applications. The use of nanophotonic materials brings an improvement of signal-to-noise ratios in detection and greater penetration depths for the treatment of deep-seated tumours [1-3]. Quantum dots (QDs) with broad absorption spectra and narrow emission bands are the excellent nanophotonic labels for FRET applications. They have a quantum yield close to 100%; high singleand two-photon molar extinction coefficients, and photoresistance. To ensure cell specificity, QDs are normally bound to recognition molecules, such as antibodies, aptamers or peptides. Single-domain antibodies (sd-Abs) are the smallest antibody fragments capable of binding their antigens, they diffuse much better into tissues than full-size Abs. Because of these advantages, we have conjugated QDs to sd-Abs in a highly oriented fashion, with all antigen binding sites facing outwards, which con-siderably increases the nanoprobe sensitivity and possible therapeutic use in oncology and demonstrated their advantages in cancer cell imaging and the micrometastases detection [3]. The possibility of increasing the Forster resonance energy transfer (FRET) efficiency is emerging in sensing and diagnostics. Light–matter coupling in microcavities leads to the formation of two new “hybrid” light–matter (polaritonic) states, instead of the two original molecular and electromagnetic field energy states. A strong coupling between light and matter can be controlled by fine tuning the electro-magnetic modes of the microresonator; it has been also demonstrated that strong coupling can modulate both distance and efficiency of FRET [4]. We have developed an adjustable unstable λ/2 Fabry-Perot microresonator with a convex metal mirror [5] satisfying the flat-parallelism conditions at least at one point of the convex mirror and mini-mises the adjustable mode volume of the confined electromagnetic field with the nm-accuracy. The strong light-matter coupling between the optical modes of a tuneable microcavity and the excitonic transitions of two closely located donor and acceptor molecules have shown that the energy states and relaxation pathways of the systems with strong dipole–dipole interaction can be altered by strong coupling of their exciton transitions to the cavity photon [6]: (1) We have demonstrated a significant increase in the efficiency of energy transfer from the donor to the acceptor exciton reservoir, which tends to be unity inside the microcavity. (2) We have shown the polariton-assisted energy state inversion and energy flow alteration thus demonstrating the so-called “carnival effect”, where the donor and acceptor reverse their roles. We speculate that these findings will pave the way to new applications of strong coupling in optically controlled FRET-based sensing and diagnostics with the ultra-small conjugates of sdAbs and QDs.

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Текст научной работы на тему «Nanophotonic detection of tumor markers and micrometastases with conjugates of single-domaine antibodies and quantum dots»

The 30th International Conference on Advanced Laser Technologies

ALT'23

P-II

Prof. Igor Nabiev

University of Reims Champagne-Ardenne, Reims, France National Research Nuclear University MEPHI, Moscow, Russia

Title: Nanophotonic detection of tumor markers and micrometastases with conjugates of single-domaine antibodies and quantum dots

Abstract

To improve cancer prognosis, early detection of the disease is one of the main purposes in diagnostic approaches. In this regard, the rapidly progressing field of nanotechnology is considered a powerful tool in cancer diagnostic and therapeutic applications. The use of nanophotonic materials brings an improvement of signal-to-noise ratios in detection and greater penetration depths for the treatment of deep-seated tumours [1-3]. Quantum dots (QDs) with broad absorption spectra and narrow emission bands are the excellent nanophotonic labels for FRET applications. They have a quantum yield close to 100%; high single- and two-photon molar extinction coefficients, and photoresistance. To ensure cell specificity, QDs are normally bound to recognition molecules, such as antibodies, aptamers or peptides. Single-domain antibodies (sd-Abs) are the smallest antibody fragments capable of binding their antigens, they diffuse much better into tissues than full-size Abs. Because of these advantages, we have conjugated QDs to sd-Abs in a highly oriented fashion, with all antigen binding sites facing outwards, which considerably increases the nanoprobe sensitivity and possible therapeutic use in oncology and demonstrated their advantages in cancer cell imaging and the micrometastases detection [3].

The possibility of increasing the Forster resonance energy transfer (FRET) efficiency is emerging in sensing and diagnostics. Light-matter coupling in microcavities leads to the formation of two new "hybrid" light-matter (polaritonic) states, instead of the two original molecular and electromagnetic field energy states. A strong coupling between light and matter can be controlled by fine tuning the electromagnetic modes of the microresonator; it has been also demonstrated that strong coupling can modulate both distance and efficiency of FRET [4].

We have developed an adjustable unstable A/2 Fabry-Perot microresonator with a convex metal mirror [5] satisfying the flat-parallelism conditions at least at one point of the convex mirror and minimises the adjustable mode volume of the confined electromagnetic field with the nm-accuracy.

The strong light-matter coupling between the optical modes of a tuneable microcavity and the excitonic transitions of two closely located donor and acceptor molecules have shown that the energy states and relaxation pathways of the systems with strong dipole-dipole interaction can be altered by strong coupling of their exciton transitions to the cavity photon [6]:

(1) We have demonstrated a significant increase in the efficiency of energy transfer from the donor to the acceptor exciton reservoir, which tends to be unity inside the microcavity.

(2) We have shown the polariton-assisted energy state inversion and energy flow alteration thus demonstrating the so-called "carnival effect", where the donor and acceptor reverse their roles.

We speculate that these findings will pave the way to new applications of strong coupling in optically controlled FRET-based sensing and diagnostics with the ultra-small conjugates of sdAbs and

QDs.

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