A. P. Sviridov

Radio frequency radiation-induced hyperthermia using Si nanoparticle-based sensitizers for mild cancer therapy.

Offering mild, non-invasive and deep cancer therapy modality, radio frequency (RF) radiation-induced hyperthermia lacks for efficient biodegradable RF sensitizers to selectively target cancer cells and thus avoid side effects. Here, we assess crystalline silicon (Si) based nanomaterials as sensitizers for the RF-induced therapy. Using nanoparticles produced by mechanical grinding of porous silicon and ultraclean laser-ablative synthesis, we report efficient RF-induced heating of aqueous suspensions of the nanoparticles to temperatures above 45-50°C under relatively low nanoparticle concentrations (<1 mg/mL) and RF radiation intensities (1–5 W/cm2). For both types of nanoparticles the heating rate was linearly dependent on nanoparticle concentration, while laser-ablated nanoparticles demonstrated a remarkably higher heating rate than porous silicon-based ones for the whole range of the used concentrations from 0.01 to 0.4 mg/mL. The observed effect is explained by the Joule heating due to the generation of electrical currents at the nanoparticle/water interface. Profiting from the nanoparticle-based hyperthermia, we demonstrate an efficient treatment of Lewis lung carcinoma in vivo. Combined with the possibility of involvement of parallel imaging and treatment channels based on unique optical properties of Si-based nanomaterials, the proposed method promises a new landmark in the development of new modalities for mild cancer therapy.

Photoluminescent biocompatible silicon nanoparticles for cancer theranostic applications

Silicon nanoparticles (SiNPs) obtained by mechanical grinding of porous silicon have been used for visualization of living cells in vitro. It was found that SiNPs could penetrate into the cells without any cytotoxic effect up to the concentration of 100 μg/ml. The cell cytoplasm was observed to be filled by SiNPs, which exhibited bright photoluminescence at 1.6 eV. SiNPs could also act as photosensitizers of the singlet oxygen generation, which could be used in the photodynamic therapy of cancer. These properties of SiNPs are discussed in view of possible applications in theranostics (both in therapy and in diagnostics).

Porous silicon nanoparticles as sensitizers for ultrasonic hyperthermia

Aqueous suspensions of porous silicon nanoparticles (NPs) with average size ∼100 nm and concentration ∼1 g/L undergo significant heating as compared with pure water under therapeutic ultrasonic (US) irradiation with frequencies of 1–2.5 MHz and intensities of 1–20 W/cm2. This effect is explained by taking into account the efficient absorption of US energy by NPs. The observed US-induced heating of biodegradable NPs is promising for applications in ultrasonic hyperthermia of tumors.

Lowering of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles for sonodynamic therapy applications

A significant decrease of the cavitation threshold in aqueous suspensions of porous silicon nanoparticles (PSi NPs) with sizes about 100 nm as compared with pure water was observed for ultrasound irradiation (USI) with therapeutic frequency (0.88 MHz) and intensities (about 1 W/cm2). This effect is explained by porous morphology of PSi NPs, which promotes the nucleation of cavitation bubbles. In vitro experiments revealed a suppression of the proliferation of cancer cells with the introduced PSi NPs after exposure to USI related to the enhanced cavitation processes, which led to the cell destruction. The obtained results demonstrate that PSi NPs are prospective for applications as sonosensitizers in mild cancer therapy.

Silicon Nanoparticles as Amplifiers of the Ultrasonic Effect in Sonodynamic Therapy

The possibility of using mesoporous silicon nanoparticles as amplifiers (sensitizers) of therapeutic ultrasonic exposure were studied experimentally in vitro and in vivo. The combination of nanoparticles and ultrasound led to a significant inhibition of Hep-2 cancer cell proliferation and Lewis lung carcinoma growth in mice. These results indicated good prospects of using silicon nanoparticles as sensitizers for sonodynamic therapy of tumors.

Selectively Modified Porous Silicon Nanoparticles as Sonosensitizers of Therapeutic Ultrasound

1 Lomonosov Moscow State University, Department of Physics 119991 Moscow, Russia 2 University of Eastern Finland, Department of Applied Physics 70211, Kuopio, Finland 3 National Research Nuclear University “MEPhI” (Moscow Engineering Physics Institute), International Laboratory “BioNanophotonics” 115409 Moscow, Russia asagittarius89@gmail.com; k.tamarov@gmail.com; victor_timoshenk@mail.ru; andreev@acs366.phys.msu.ru

Nano-Air Seeds Trapped in Mesoporous Janus Nanoparticles Facilitate Cavitation and Enhance Ultrasound Imaging

The current contrast agents utilized in ultrasound (US) imaging are based on microbubbles which suffer from a short lifetime in systemic circulation. The present study introduces a new type of contrast agent for US imaging based on bioresorbable Janus nanoparticles (NPs) that are able to generate microbubbles in situ under US radiation for extended time. The Janus NPs are based on porous silicon (PSi) that was modified via a nanostopper technique. The technique was exploited to prepare PSi NPs which had hydrophobic pore walls (inner face), while the external surfaces of the NPs (outer face) were hydrophilic. As a consequence, when dispersed in an aqueous solution, the Janus NPs contained a substantial amount of air trapped in their nanopores. The specific experimental setup was developed to prove that these nano air seeds were indeed acting as nuclei for microbubble growth during US radiation. Using the setup, the cavitation thresholds of the Janus NPs were compared to their completely hydrophilic counterparts by detecting the subharmonic signals from the microbubbles. These experiments and the numerical simulations of the bubble dynamics demonstrated that the Janus NPs generated microbubbles with a radii of 1.1 μm. Furthermore, the microbubbles generated by the NPs were detected with a conventional medical ultrasound imaging device. Long systemic circulation time was ensured by grafting the NPs with two different PEG polymers, which did not affect adversely the microbubble generation. The present findings represent an important landmark in the development of ultrasound contrast agents which possess the properties for both diagnostics and therapy.

Effects of ultrasonic cavitation and heat deposition in aqueous suspensions of mesoporous silicon nanoparticles

The effects of ultrasonic cavitation and heat deposition in aqueous suspensions of mesoporous silicon nanoparticles were experimentally investigated using an original setup enabling precise temperature control and registration of cavitation by harmonics analysis of the transmitted signal. The obtained results reveal significant lowering of cavitation thresholds and heating of suspensions as compared to pure water.