Developing Chlorin/Arylaminoquinazoline Conjugates with Nanomolar Activity for Targeted Photodynamic Therapy: Design, Synthesis, SAR, and Biological Evaluation.

In this report, we developed novel chlorin/arylaminoquinazoline conjugates for targeted photodynamic therapy of cancer. The synthesized photosensitizers consisted of chlorin- metallocomplexes (Zn, In, or Pd) conjugated with arylaminoquinazoline ligands with high affinity for epidermal growth factor receptors (EGFR). Additionally, the selectivity and antitumor properties of the conjugates were investigated in the EGFR-expressing A431 human tumor cell line .

MPS blockade with liposomes controls pharmacokinetics of nanoparticles in a size-dependent manner.

Pharmacokinetics of nanomedicines can be improved by a temporal blockade of mononuclear phagocyte system (MPS) through the interaction with other biocompatible nanoparticles. Liposomes are excellent candidates as blocking agents, but the efficiency of the MPS blockade can greatly depend on the liposome properties. Here, we investigated the dependence of the efficiency of the induced MPS blockadeandon the size of blocking liposomes in the 100-500 nm range.

Laser-synthesized plasmonic HfN-based nanoparticles as a novel multifunctional agent for photothermal therapy.

Hafnium nitride nanoparticles (HfN NPs) can offer appealing plasmonic properties at the nanoscale, but the fabrication of stable water-dispersible solutions of non-toxic HfN NPs exhibiting plasmonic features in the window of relative biological transparency presents a great challenge. Here, we demonstrate a solution to this problem by employing ultrashort (femtosecond) laser ablation from a HfN target in organic solutions, followed by a coating of the formed NPs with polyethylene glycol (PEG) and subsequent dispersion in water. We show that the fabricated NPs exhibit plasmonic absorption bands with maxima around 590 nm, 620 nm, and 650 nm, depending on the synthesis environment (ethanol, acetone, and acetonitrile, respectively), which are largely red-shifted compared to what is expected from pure HfN NPs.

Boron Nanoparticle-Enhanced Proton Therapy: Molecular Mechanisms of Tumor Cell Sensitization.

Boron-enhanced proton therapy has recently appeared as a promising approach to increase the efficiency of proton therapy on tumor cells, and this modality can further be improved by the use of boron nanoparticles (B NPs) as local sensitizers to achieve enhanced and targeted therapeutic outcomes. However, the mechanisms of tumor cell elimination under boron-enhanced proton therapy still require clarification. Here, we explore possible molecular mechanisms responsible for the enhancement of therapeutic outcomes under boron NP-enhanced proton therapy.

Binary Proton Therapy of Ehrlich Carcinoma Using Targeted Gold Nanoparticles.

Proton therapy can treat tumors located in radiation-sensitive tissues. This article demonstrates the possibility of enhancing the proton therapy with targeted gold nanoparticles that selectively recognize tumor cells. Au-PEG nanoparticles at concentrations above 25 mg/L and 4 Gy proton dose caused complete death of EMT6/P cells in vitro.

Rediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery.

Rapid uptake of nanoparticles by mononuclear phagocyte system (MPS) significantly hampers their therapeutic efficacy. Temporal MPS blockade is one of the few ways to overcome this barrier - the approach rediscovered many times under different names but never extensively used in clinic. Using meta-analysis of the published data we prove the efficacy of this technique for enhancing particle circulation in blood and their delivery to tumours, describe a century of its evolution and potential combined mechanism behind it.

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.

Laser-Synthesized Elemental Boron Nanoparticles for Efficient Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is one of the most appealing radiotherapy modalities, whose localization can be further improved by the employment of boron-containing nanoformulations, but the fabrication of biologically friendly, water-dispersible nanoparticles (NPs) with high boron content and favorable physicochemical characteristics still presents a great challenge. Here, we explore the use of elemental boron (B) NPs (BNPs) fabricated using the methods of pulsed laser ablation in liquids as sensitizers of BNCT. Depending on the conditions of laser-ablative synthesis, the used NPs were amorphous (a-BNPs) or partially crystallized (pc-BNPs) with a mean size of 20 nm or 50 nm, respectively.

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeuticRe 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)-NHMOFs and conjugated them with clinically utilized radionuclideRe.

Boron Nanoparticle-Enhanced Proton Therapy for Cancer Treatment.

Proton therapy is one of the promising radiotherapy modalities for the treatment of deep-seated and unresectable tumors, and its efficiency can further be enhanced by using boron-containing substances. Here, we explore the use of elemental boron (B) nanoparticles (NPs) as sensitizers for proton therapy enhancement. Prepared by methods of pulsed laser ablation in water, the used B NPs had a mean size of 50 nm, while a subsequent functionalization of the NPs by polyethylene glycol improved their colloidal stability in buffers.

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism.

Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism.

Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment.

Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes.

Polymer-coated BiOCl nanosheets for safe and regioselective gastrointestinal X-ray imaging.

Bismuth-based compounds are considered to be the best candidates for computed tomography (CT) imaging of gastrointestinal (GI) tract due to high X-ray absorption. Here, we report the introduction of polymer-coated bismuth oxychloride (BiOCl) nanosheets for highly efficient CT imaging in healthy mice and animal with colitis. We demonstrate simple, low cost and fast aqueous synthesis protocol which provides gram-quantity yield of chemically stable BiOCl nanosheets.

Phage-mimicking nanoagents for rapid depolymerase specificity screening against multidrug resistant bacteria.

With the rise of drug resistance, bacteriophages and bacteriophage-derived proteins may become an efficient successor to traditional antibiotics. While the enormous natural diversity of the phages allows matching virtually any bacteria, identification of the potentially life-saving phage is currently a tedious and time-consuming challenge that often cannot be performed within a reasonable time. Here we show a rapid 1-min bacteriophage screening assay based on specially constructed phage-mimicking nanoagents and surface plasmon resonance effect.

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 (HBO) as an oxidation by-product coating the nanoparticles, which acts to stabilize the elemental boron NPs dispersion.

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.

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.

Laser-Ablative Synthesis of Ultrapure Magneto-Plasmonic Core-Satellite Nanocomposites for Biomedical Applications.

The combination of magnetic and plasmonic properties at the nanoscale promises the development of novel synergetic image-guided therapy strategies for the treatment of cancer and other diseases, but the fabrication of non-contaminated magneto-plasmonic nanocomposites suitable for biological applications is difficult within traditional chemical methods. Here, we describe a methodology based on laser ablation from Fe target in the presence of preliminarily ablated water-dispersed Au nanoparticles (NPs) to synthesize ultrapure bare (ligand-free) core-satellite nanostructures, consisting of large (several tens of nm) Fe-based core decorated by small (mean size 7.5 nm) Au NPs.

DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice.

Near-infrared phototherapy has great therapeutic potential for cancer treatment. However, for efficient application, in vivo photothermal agents should demonstrate excellent stability in blood and targeted delivery to pathological tissue. Here, we demonstrated that stable bovine serum albumin-coated gold mini nanorods conjugated to a HER2-specific designed ankyrin repeat protein, DARPin_9-29, selectively accumulate in HER2-positive xenograft tumors in mice and lead to a strong reduction in the tumor size when being illuminated with near-infrared light.

Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study.

Safe application of nanoparticles in medicine requires full understanding of their pharmacokinetics including catabolism in the organism. However, information about nanoparticle degradation is still scanty due to difficulty of long-term measurements by invasive techniques. Here, we describe a magnetic spectral approach for monitoring of magnetic particle (MP) degradation.

Laser-synthesized TiN nanoparticles for biomedical applications: Evaluation of safety, biodistribution and pharmacokinetics.

Having plasmonic absorption within the biological transparency window, titanium nitride (TiN) nanoparticles (NPs) can potentially outperform gold counterparts in phototheranostic applications, but characteristics of available TiN NPs are still far from required parameters. Recently emerged laser-ablative synthesis opens up opportunities to match these parameters as it makes possible the production of ultrapure low size-dispersed spherical TiN NPs, capable of generating a strong phototherapy effect under 750-800 nm excitation. This study presents the first assessment of toxicity, biodistribution and pharmacokinetics of laser-synthesized TiN NPs.

In vivo blockade of mononuclear phagocyte system with solid nanoparticles: Efficiency and affecting factors.

Smart nanomaterials, contrast nanoparticles and drug nanocarriers of advanced targeting architecture were designed for various biomedical applications. Most of such agents demonstrate poor pharmacokinetics in vivo due to rapid elimination from the bloodstream by cells of the mononuclear phagocyte system (MPS). One of the promising methods to prolong blood circulation of the nanoparticles without their modification is MPS blockade.

Dual Regioselective Targeting the Same Receptor in Nanoparticle-Mediated Combination Immuno/Chemotherapy for Enhanced Image-Guided Cancer Treatment.

When combined with immunotherapy, image-guided targeted delivery of chemotherapeutic agents is a promising direction for combination cancer theranostics, but this approach has so far produced only limited success due to a lack of molecular targets on the cell surface and low therapeutic index of conventional chemotherapy drugs. Here, we demonstrate a synergistic strategy of combination immuno/chemotherapy in conditions of dual regioselective targeting, implying vectoring of two distinct binding sites of a single oncomarker (here, HER2) with theranostic compounds having a different mechanism of action. We use: (i) PLGA nanoformulation, loaded with an imaging diagnostic fluorescent dye (Nile Red) and a chemotherapeutic drug (doxorubicin), and functionalized with affibody Z (8 kDa); (ii) bifunctional genetically engineered DARP-LoPE (42 kDa) immunotoxin comprising of a low-immunogenic modification of therapeutic exotoxin A (LoPE) and a scaffold targeting protein, DARPin9.