Nuclear nanomedicine using Si nanoparticles as safe and effective carriers of 188Re radionuclide for cancer therapy

Abstract

Nuclear nanomedicine, with its targeting ability and heavily loading capacity, along with its enhanced retention to avoid rapid clearance as faced with molecular radiopharmaceuticals, provides unique opportunities to treat tumors and metastasis. Despite these promises, this field has seen limited activities, primarily because of a lack of suitable nanocarriers, which are safe, excretable and have favorable pharmacokinetics to efficiently deliver and retain radionuclides in a tumor. Here, we introduce biodegradable laser-synthesized Si nanoparticles having round shape, controllable low-dispersion size, and being free of any toxic impurities, as highly suitable carriers of therapeutic 188Re radionuclide. The conjugation of the polyethylene glycol-coated Si nanoparticles with radioactive 188Re takes merely 1 hour, compared to its half-life of 17 hours. When intravenously administered in a Wistar rat model, the conjugates demonstrate free circulation in the blood stream to reach all organs and target tumors, which is radically in contrast with that of the 188Re salt that mostly accumulates in the thyroid gland. We also show that the nanoparticles ensure excellent retention of 188Re in tumor, not possible with the salt, which enables one to maximize the therapeutic effect, as well as exhibit a complete time-delayed conjugate bioelimination. Finally, our tests on rat survival demonstrate excellent therapeutic effect (72% survival compared to 0% of the control group). Combined with a series of imaging and therapeutic functionalities based on unique intrinsic properties of Si nanoparticles, the proposed biodegradable complex promises a major advancement in nuclear nanomedicine.

Localized infrared radiation-induced hyperthermia sensitized by laser-ablated silicon nanoparticles for phototherapy applications

“…(i) In contrast to porous silicon nanostructures, laser-synthesized Si-NPs have ideal spherical shape and are low size-dispersed, which promises a much improved transport in biological systems in vivo [27]; (ii) Laser-synthesized Si-NPs can have a defect-rich polycrystalline structure, which conditions a much faster dissolution and excretion of these nanoparticles from the body in vivo (4-7 days [22,23] compared to more than 6 weeks in the case of porous silicon [35]); (iii) Laser-synthesized Si-NPs are produced in ultrapure deionized water, which excludes any contamination of nanoparticles by toxic by-products of synthesis, as it takes place in many alternative methods [11,12,16]; (iv) Laser-synthesized Si-NPs can offer a series of imaging [5,26] and therapy (Refs. [9,19,27]) modalities, which can be enabled in parallel with the considered photothermal modality.…”

“…On the other hand, laser-synthesized Si NPs can be efficient sensitizers of therapeutic modalities such as PDT [7] and RF radiation-induced hyperthermia [9], as well as serve as carriers of therapeutic radionuclides [27]. Such a combination of different modalities in one Si-based nanoformulation looks as an effective strategy to develop novel theranostic (therapy + diagnostics) agents for biomedical applications.…”

Bare laser-synthesized palladium–gold alloy nanoparticles as efficient electrocatalysts for glucose oxidation for energy conversion applications

“…For the synthesis of PdAu NPs we adapted methods of ultrashort laser ablation and fragmentation in liquid ambience, which were earlier used for the preparation of bare Au [16][17][18][19] and Si 32,33 NPs. Our approach for nanoalloy synthesis was based on the co-fragmentation of the mixture of two types of metallic nanoparticles.…”

Laser-Ablative Synthesis of Isotope-Enriched Samarium Oxide Nanoparticles for Nuclear Nanomedicine

“…Making possible fast production of bare (uncovered) NPs in colloidal state with almost any composition, pulsed laser ablation in liquids [12][13][14][15][16][17] (PLAL) provides one of best alternatives to satisfy the above-stated demands. As an example, we recently showed that the technique of femtosecond laser ablation in liquids can be used for the fabrication of a variety of ultrapure, biologically-friendly nanomaterials, including gold NPs [16,[18][19][20][21][22], titanium nitride (TiN) NPs [23], silicon NPs [24][25][26][27] and organic polymer NPs [28]. In many cases, such nanoparticles can provide superior properties for catalytic [20], energy and biomedical [29,30] applications, compared to nanomaterials synthesized by conventional chemical methods, and other methods.…”