Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy.

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g-1 cm-1 at 808 nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic188Re radionuclide for nuclear medicine.

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH2MOFs and conjugated them with clinically utilized radionuclide188Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg-1. Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH2for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine.

Laser-ablative aqueous synthesis and characterization of elemental boron nanoparticles for biomedical applications.

Boron-based nano-formulations look very promising for biomedical applications, including photo- and boron neutron capture therapies, but the fabrication of non-toxic water-dispersible boron nanoparticles (NPs), which contain the highest boron atom concentration, is difficult using currently available chemical and plasma synthesis methods. Here, we demonstrate purely aqueous synthesis of clean boron NPs by methods of femtosecond laser ablation from a solid boron target in water, thus free of any toxic organic solvents, and characterize their properties. We show that despite highly oxidizing water ambience, the laser-ablative synthesis process follows an unusual scenario leading to the formation of boron NPs together with boric acid (H3BO3) as an oxidation by-product coating the nanoparticles, which acts to stabilize the elemental boron NPs dispersion. We then demonstrate the purification of boron NPs from residual boric acid in deionized water, followed by their coating with polyethylene glycol to improve colloidal stability and biocompatibility. It was found that the formed NPs have a spherical shape with averaged size of about 37 nm, and are composed of elemental boron in mostly amorphous phase with the presence of certain crystalline fraction. The synthesized NPs demonstrate low toxicity and exhibit strong absorption in the NIR window of relative tissue transparency, promising their use in photoacoustic imaging and phototherapy, in addition to their promise for neutron capture therapy. This combined potential ability of generating imaging and therapy functionalities makes laser-synthesized B NPs a very promising multifunctional agent for biomedical applications.

Laser Synthesized Core-Satellite Fe-Au Nanoparticles for Multimodal In Vivo Imaging and In Vitro Photothermal Therapy.

Hybrid multimodal nanoparticles, applicable simultaneously to the noninvasive imaging and therapeutic treatment, are highly demanded for clinical use. Here, Fe-Au core-satellite nanoparticles prepared by the method of pulsed laser ablation in liquids were evaluated as dual magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and as sensitizers for laser-induced hyperthermia of cancer cells. The biocompatibility of Fe-Au nanoparticles was improved by coating with polyacrylic acid, which provided excellent colloidal stability of nanoparticles with highly negative ζ-potential in water (-38 ± 7 mV) and retained hydrodynamic size (88 ± 20 nm) in a physiological environment. The ferromagnetic iron cores offered great contrast in MRI images with r2 = 11.8 ± 0.8 mM-1 s-1 (at 1 T), while Au satellites showed X-ray attenuation in CT. The intravenous injection of nanoparticles enabled clear tumor border visualization in mice. Plasmonic peak in the Fe-Au hybrids had a tail in the near-infrared region (NIR), allowing them to cause hyperthermia under 808 nm laser exposure. Under NIR irradiation Fe-Au particles provided 24.1 °C/W heating and an IC50 value below 32 µg/mL for three different cancer cell lines. Taken together, these results show that laser synthesized Fe-Au core-satellite nanoparticles are excellent theranostic agents with multimodal imaging and photothermal capabilities.

Macrophage blockade using nature-inspired ferrihydrite for enhanced nanoparticle delivery to tumor.

The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite - a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.