Energy Partitioning in Multicomponent Nanoscintillators for Enhanced Localized Radiotherapy

Abstract

Multicomponent nanomaterials consisting of dense scintillating particles functionalized by or embedding optically active conjugated photosensitizers (PSs) for cytotoxic reactive oxygen species (ROS) have been proposed in the last decade as coadjuvant agents for radiotherapy of cancer. They have been designed to make scintillation-activated sensitizers for ROS production in an aqueous environment under exposure to ionizing radiations. However, a detailed understanding of the global energy partitioning process occurring during the scintillation is still missing, in particular regarding the role of the non-radiative energy transfer between the nanoscintillator and the conjugated moieties which is usually considered crucial for the activation of PSs and therefore pivotal to enhance the therapeutic effect. We investigate this mechanism in a series of PS-functionalized scintillating nanotubes where the non-radiative energy transfer yield has been tuned by control of the intermolecular distance between the nanotube and the conjugated system. The obtained results indicate that non-radiative energy transfer has a negligible effect on the ROS sensitization efficiency, thus opening the way to the development of different architectures for breakthrough radiotherapy coadjutants to be tested in clinics.

Keywords: energy transfer; nanomaterials; radiotherapy; scintillators; singlet oxygen.

Figure 1

(a) Synthesis of multicomponent scintillating nanotubes (NTs) for PDT-enhanced radiotherapy achieved by the use of an SO () PS. (b) Photophysics of the sensitization of SO production under exposure to ionizing radiation. The free electrons and holes generated by interaction between the ionizing radiation and the NT recombine directly on the NT and on the PS. The latter is promoted to its excited-state singlet (S_n*) or triplet (T_n*) with a ratio of 1:3. The energy stored in the NT can be therefore transferred by non-radiative energy transfer (ET_nr) producing additional PS molecules in the S₁* state. The PS molecules in the S₁* state can subsequently experience intersystem crossing (ISC) that further populates the T₁* state. From PS in the triplet state, the energy is transferred by a second non-radiative energy transfer step to molecular oxygen, which is promoted to its excited singlet state . (c) Sketch of ET_nr active and ET_nr inactive multicomponent scintillating NTs realized by incrementing the intermolecular distance between the NT and the PS molecules.

Figure 2

(a) Transmission electron microscopy (TEM) image of scintillating chrysotile NTs and their size distribution (inset). (b) On the left, the PL (dashed–dotted line, exc. 250 nm) and radioluminescence (RL, solid line) spectrum of the NT under soft X-ray exposure (dashed–dotted line). On the right, absorption (dashed line) and PL (solid line) spectra of the conjugated chromophore Rhodamine Red C₂ maleimide selected as the model SO PS. (c) Attenuated reflectance FT-IR spectra of NTs and the multicomponent nanoscintillator series obtained by tuning the PS-to-NT intermolecular distance from 5 Å (NT-5*) to 46 Å (NT-46*). The asterisks mark the sample where Rhodamine Red C₂ maleimide is substituted with rhodamine B. Shaded areas mark the characteristic IR mode of the NT (gray at around 1000 and 4700 cm^–1) and of the PS (orange, 2300–2500 cm^–1). (d) PL of multicomponent nanoscintillators as a function of the NT-to-PS intermolecular distance under UV excitation at 250 nm. The spectra are normlized to the PS emission peak in the red spectral range. (e) PL intensity decay in time recorded at 430 nm under pulsed excitation at 250 nm of NTs and the functionalized NT sample series. The inset is a digital picture of the NT-20 sample under daylight.

Figure 3

(a) RL spectra of the multicomponent nanoscintillator series as a function of the PS-to-NT intermolecular distance, normalized to the residual PS emission intensity. (b) Scintillation pulses recorded at ca. 620 nm under pulsed X-ray excitation at 40 keV. (c) PL intensity decay at 620 nm under pulsed excitation at 250 nm. (d) Relative increment of the SO concentration as a function of the irradiation time under soft X-rays for the NT-20 sample (4.0 mg/mL, PBS). The SO increment has been monitored by recording the PL of the SO optical probe SOSG under simultaneous CW laser excitation at 473 nm (inset). (e) NT-to-PS energy transfer yield (ϕ_ET^nr, dots), relative scintillation yield () of the PS, and SO relative sensitization ability after 600 s of exposure to soft X-rays for the multicomponent nanoscintillator series, as a function of the NT-to-PS intermolecular distance. Error bars are put as the mean standard deviation calculated on a N = 3 measurement replica.