K. P. Tamarov

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.

Temperature responsive porous silicon nanoparticles for cancer therapy - spatiotemporal triggering through infrared and radiofrequency electromagnetic heating.

One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals. TOC IMAGE The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo.

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.

Optical Properties of Serum Albumin Water Solutions, Containing Mesoporous Silicon Particles

The interaction of molecules of bovine serum albumin (BSA) with silicon nanoparticles (SiNPs) was studied in water solutions of them at different pH values. The data of photon correlation spectroscopy and IR spectroscopy of studied solutions indicate the absence of interaction between BSA and SiNPs in the pH range 3–7, which is attested to by the experimentally obtained character of the pH dependence of the translational diffusion coefficient Dt and by the absence of hydrogen bonds between the protein carbonyl groups and the OH groups on the surface of mesoporous silicon nanoparticles. The obtained data may play a leading role in further in vivo application of silicon nanoparticles.

Approaches to improve the biocompatibility and systemic circulation of inorganic porous nanoparticles

The exploitation of various inorganic nanoparticles as drug carriers and therapeutics is becoming increasingly common. The first issue to be considered with regard to the nanomaterials being utilized in medicine centers on their safety. The functionality of nanocarriers in real-life environments explains the enthusiasm for their use. Several functionalities are typically added onto nanocarriers but the most crucial feature of those carriers intended to be administered intravenously is that they should possess a long residence time in blood circulation. The present review focusses on the mesoporous nanoparticles due to their great promise in nanomedicine and concentrates on their coatings because it is the outmost layer which dictates their first interactions with the surroundings and often determines their biofate.

Scalable Synthesis of Biodegradable Black Mesoporous Silicon Nanoparticles for Highly Efficient Photothermal Therapy

Porous silicon (PSi) has attracted wide interest as a potential material for various fields of nanomedicine. However, until now, the application of PSi in photothermal therapy has not been successful due to its low photothermal conversion efficiency. In the present study, biodegradable black PSi (BPSi) nanoparticles were designed and prepared via a high-yield and simple reaction. The PSi nanoparticles possessed a low band gap of 1.34 eV, a high extinction coefficient of 13.2 L/g/cm at 808 nm, a high photothermal conversion efficiency of 33.6%, good photostability, and a large surface area. The nanoparticles had not only excellent photothermal properties surpassing most of the present inorganic photothermal conversion agents (PCAs) but they also displayed good biodegradability, a common problem encountered with the inorganic PCAs. The functionality of the BPSi nanoparticles in photothermal therapy was verified in tumor-bearing mice in vivo. These results showed clearly that the photothermal treatment was highly efficient to inhibit tumor growth. The designed PCA material of BPSi is robust, easy to prepare, biocompatible, and therapeutically extremely efficient and it can be integrated with several other functionalities on the basis of simple silicon chemistry.

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.