Photoacoustic imaging (PAI) is a rapidly growing imaging modality, which combines high contrast of optical absorption with deep penetration depth of ultrasound. When combined with endogenous contrast agents based on light-absorbing nanoparticles (NPs), PAI can visualize various biological processes and tissues. Here, we describe a simple experimental setup based on a tissue-mimicking phantom with flexible optical properties for studying photoacoustic (PA) response of NPs. Our approach is based on a polyacrylamide gel phantom with independently variable optical absorption and scattering. The phantom allows one to model and study PA response of contrast agents with diverse spatial distributions and concentrations. To demonstrate high potential of the developed experimental setup, we prepared a phantom with optical properties matching human prostate tissue and performed a PAI of laser-synthesized titanium nitride (TiN) NPs, distributed in a disk-shaped area, located 10 mm under the phantom surface. We believe that our approach will contribute the successful development of clinical PAI with NPs-based contrast agents.
Titanium nitride (TiN) nanoparticles (NPs) prepared by methods of laser ablation in liquids present a novel object, which promises attractive biomedical applications. Here, we review our recent advances in the elaboration of femtosecond laser ablation technique from a TiN target in liquid medium (here, isopropanol) to maximize the efficiency of TiN NPs synthesis and optimize their characteristics. Our experiments showed that the synthesis productivity is dependent on lateral velocity of laser beam scanning during laser ablation with the achievement of productivity saturation at a certain relatively high velocity. The observed phenomenon was attributed to the interaction of laser pulses with cavitation bubbles generated during the ablation process. In addition, we assessed photo heating properties of the synthesized TiN NPs in the near-IR range. It was found that TiN NPs with sizes in 20-50 nm range have the highest heating rate and can be heated to maximal temperatures. As demonstrated by our recent tests in vitro and in vivo, this size range is optimal for biomedical applications, which promises successful applications of these nanoparticles in phototherapy and imaging modalities.
Newly emerging nanomaterials promise a major advancement of methods of nuclear and radiative medicine for cancer treatment, as they can be used as carriers of diagnostic or therapeutic radionuclides, contrast agents in nuclear imaging modalities (PET, SPECT) or sensitizers of radiative therapies (X-ray, ion beams, etc.). However, nanotechnology-based approaches have reported a limited success so far due to a lack of suitable functional nanoformulations, which are safe, non-toxic, excretable from the body and have favorable pharmacokinetics for effective accumulation in the tumor. As follows from the results of our on-going research activities, many of the above-stated problems can we solved by the employment of nanomaterials fabricated by clean laser-ablative synthesis. Here, we review our recent data on some promising nanomaterials, prepared by this method, including biodegradable silicon (Si) nanoparticles (NPs), 152Sm-enriched samarium oxide NPs, and elemental bismuth (Bi) NPs, which can be used either as carriers/agents in radionuclide therapy, or sensitizers in radiative diagnostics or therapy. Advantages of proposed approach include exceptional purity and flexibility in synthesizing of NPs of required physico-chemical parameters (controlled size, shape, composition, and surface conditioning of NPs). Advances in laser-ablative fabrication of novel nanomaterials open up avenues for future implementations of nuclear and radiative medicine approaches for safe and efficient theranostics of tumors and metastasis.
Owing to a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) constitute a promising candidate for nanomedicine. However, their potential is still underexplored due to difficulties of synthesis of stable biocompatible colloids of TiN NPs. Here, we provide results of elaboration of laser-ablative synthesis of TiN NPs in liquids which can solve the problem. Laser-ablated TiN NPs have strong plasmonic peak in near-IR. We also present their first comprehensive biocompatibility assessment. The obtained results evidence high safety of laser-synthesized TiN NPs for biological systems, which promises a major advancement of phototheranostic modalities on their basis.
Radiation nanomedicine is an emerging field, which utilizes nanoformulations of high-Z elements and nuclear agents to improve therapeutic outcome and to reduce radiation dosage. This field lacks methods for controlled fabrication of biocompatible nanoformulations. Here, we present application of femtosecond laser ablation in liquids to fabricate stable colloidal solutions of ultrapure elemental Bi and isotope-enriched samarium oxide nanoparticles (NPs). The obtained spherical Bi and Sm oxide NPs have controllable size, while Bi NPs have remarkable absorption in the near-IR region. Exempt of any toxic by-products, laser-ablated Bi and Sm oxide NPs present a novel appealing nanoplatform for nuclear and radiotherapies.
Nanotechnology promises a major improvement of efficacy of nuclear medicine by targeted delivery of radioactive agents to tumors, but this approach still needs novel efficient nanoformulations to maximize diagnostic and therapeutic functions. Here, we present a two-step method of laser ablation and fragmentation in water to produce non-radioactive 152Sm-enriched samarium oxide nanoparticles (Sm NPs), which can be converted to radioactive form of 153Sm beta-emitters by neutron capture reaction. We found that laser ablation in deionized water leads to the formation of NPs having diverse morphology and broad size dispersion. To improve size characteristics of formed NPs, we applied additional femtosecond laser fragmentation step, which made possible a good control of mean NPs size under a drastic narrowing of size dispersion, and the spherical shape of formed NPs. Obtained colloidal solutions of Sm NPs were stable for several weeks after the synthesis. The formed NPs present a very promising object for nuclear nanomedicine.
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