Albumin incorporation into recognising layer of HER2-specific magnetic nanoparticles as a tool for optimal targeting of the acidic tumor microenvironment.

Cancer is unquestionably a global healthcare challenge, spurring the exporation of novel treatment approaches. In recent years, nanomaterials have garnered significant interest with the greatest hopes for targeted nanoformulations due to their cell-specific delivery, improved therapeutic efficacy, and reduced systemic toxicity for the organism. The problem of successful clinical translation of nanoparticles may be related to the fact that most in vitro tests are performed at pH values of normal cells and tissues, ranging from 7.

The influence of various polymer coatings on the in vitro and in vivo properties of PLGA nanoparticles: Comprehensive study.

Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) with various surface chemistry are widely used in biomedicine for theranostic applications. The nature of the external coating of nanoparticles has a significant influence on their efficiency as drug carriers or visualization agents. However, information about the mechanisms of nanoparticle accumulation in tumors and the influence of their surface properties on biodistribution is scarce due to the lack of systematic evaluation.

Human Blood Serum Counteracts EGFR/HER2-Targeted Drug Lapatinib Impact on Squamous Carcinoma SK-BR-3 Cell Growth and Gene Expression.

Lapatinib is a targeted therapeutic inhibiting HER2 and EGFR proteins. It is used for the therapy of HER2-positive breast cancer, although not all the patients respond to it. Using human blood serum samples from 14 female donors (separately taken or combined), we found that human blood serum dramatically abolishes the lapatinib-mediated inhibition of growth of the human breast squamous carcinoma SK-BR-3 cell line.

Targeted PLGA-Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors.

Targeted medicine uses the distinctive features of cancer cells to find and destroy tumors. We present human epidermal growth factor receptor 2 (HER2)-targeted PLGA-chitosan nanoparticles for cancer therapy and visualization. Loading with two near-infrared (NIR) dyes provides imaging in the NIR transparency window and phototherapy triggered by 808 nm light.

Topological Darkness: How to Design a Metamaterial for Optical Biosensing with Ultrahigh Sensitivity.

Due to the absence of labels and fast analyses, optical biosensors promise major advances in biomedical diagnostics, security, environmental, and food safety applications. However, the sensitivity of the most advanced plasmonic biosensor implementations has a fundamental limitation caused by losses in the system and/or geometry of biochips. Here, we report a "scissor effect" in topologically dark metamaterials which is capable of providing ultrahigh-amplitude sensitivity to biosensing events, thus solving the bottleneck sensitivity limitation problem.

Surface Characteristics Affect the Properties of PLGA Nanoparticles as Photothermal Agents.

Photothermal therapy is one of the most promising and rapidly developing fields in modern oncology due to its high efficiency, localized action, and minimal invasiveness. Polymeric nanoparticles (NPs) incorporating low molecular-weight photothermal dyes are capable of delivering therapeutic agents to the tumor site, releasing them in a controlled manner, and providing tumor treatment under external light irradiation. The nanoparticle synthesis components are critically important factors that influence the therapeutically significant characteristics of polymeric NPs.

Comparative Study of Nanoparticle Blood Circulation after Forced Clearance of Own Erythrocytes (Mononuclear Phagocyte System-Cytoblockade) or Administration of Cytotoxic Doxorubicin- or Clodronate-Loaded Liposomes.

Recent developments in the field of nanomedicine have introduced a wide variety of nanomaterials that are capable of recognizing and killing tumor cells with increased specificity. A major limitation preventing the widespread introduction of nanomaterials into the clinical setting is their fast clearance from the bloodstream via the mononuclear phagocyte system (MPS). One of the most promising methods used to overcome this limitation is the MPS-cytoblockade, which forces the MPS to intensify the clearance of erythrocytes by injecting allogeneic anti-erythrocyte antibodies and, thus, significantly prolongs the circulation of nanoagents in the blood.

Targeted Two-Step Delivery of Oncotheranostic Nano-PLGA for HER2-Positive Tumor Imaging and Therapy In Vivo: Improved Effectiveness Compared to One-Step Strategy.

Therapy for aggressive metastatic breast cancer remains a great challenge for modern biomedicine. Biocompatible polymer nanoparticles have been successfully used in clinic and are seen as a potential solution. Specifically, researchers are exploring the development of chemotherapeutic nanoagents targeting the membrane-associated receptors of cancer cells, such as HER2.

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo.

Targeted nanoparticles of different origins are considered as new-generation diagnostic and therapeutic tools. However, there are no targeted drug formulations within the composition of nanoparticles approved by the FDA for use in the clinic, which is associated with the insufficient effectiveness of the developed candidates, the difficulties of their biotechnological production, and inadequate batch-to-batch reproducibility. Targeted protein self-assembling nanoparticles circumvent this problem since proteins are encoded in DNA and the final protein product is produced in only one possible way.

Lectin-Modified Magnetic Nano-PLGA for Photodynamic Therapy In Vivo.

The extreme aggressiveness and lethality of many cancer types appeal to the problem of the development of new-generation treatment strategies based on smart materials with a mechanism of action that differs from standard treatment approaches. The targeted delivery of nanoparticles to specific cancer cell receptors is believed to be such a strategy; however, there are no targeted nano-drugs that have successfully completed clinical trials to date. To meet the challenge, we designed an alternative way to eliminate tumors in vivo.

Two-Step Targeted Drug Delivery via Proteinaceous Barnase-Barstar Interface and Doxorubicin-Loaded Nano-PLGA Outperforms One-Step Strategy for Targeted Delivery to HER2-Overexpressing Cells.

Nanoparticle-based chemotherapy is considered to be an effective approach to cancer diagnostics and therapy in modern biomedicine. However, efficient tumor targeting remains a great challenge due to the lack of specificity, selectivity, and high dosage of chemotherapeutic drugs required. A two-step targeted drug delivery strategy (DDS), involving cancer cell pre-targeting, first with a first nontoxic module and subsequent targeting with a second complementary toxic module, is a solution for decreasing doses for administration and lowering systemic toxicity.

Ratiometric i-Motif-Based Sensor for Precise Long-Term Monitoring of pH Micro Alterations in the Nucleoplasm and Interchromatin Granules.

DNA-intercalated motifs (iMs) are facile scaffolds for the design of various pH-responsive nanomachines, including biocompatible pH sensors. First, DNA pH sensors relied on complex intermolecular scaffolds. Here, we used a simple unimolecular dual-labeled iM scaffold and minimized it by replacing the redundant loop nucleosides with abasic or alkyl linkers.

Fluorescent Magnetic Nanoparticles for Bioimaging through Biomimetic Surface Modification.

Nanostructured materials and systems find various applications in biomedical fields. Hybrid organo-inorganic nanomaterials are intensively studied in a wide range of areas, from visualization to drug delivery or tissue engineering. One of the recent trends in material science is biomimetic approaches toward the synthesis or modification of functional nanosystems.

Switchable targeting of solid tumors by BsCAR T cells.

The development of chimeric antigen receptor (CAR) T cell therapy has become a critical milestone in modern oncotherapy. Despite the remarkable in vitro effectiveness, the problem of safety and efficacy of CAR T cell therapy against solid tumors is challenged by the lack of tumor-specific antigens required to avoid on-target off-tumor effects. Spatially separating the cytotoxic function of CAR T cells from tumor antigen recognition provided by protein mediators allows for the precise control of CAR T cell cytotoxicity.

Photothermal Therapy with HER2-Targeted Silver Nanoparticles Leading to Cancer Remission.

Nanoparticles exhibiting the localized surface plasmon resonance (LSPR) phenomenon are promising tools for diagnostics and cancer treatment. Among widely used metal nanoparticles, silver nanoparticles (Ag NPs) possess the strongest light scattering and surface plasmon strength. However, the therapeutic potential of Ag NPs has until now been underestimated.

Effect of Surface Modification of Multifunctional Nanocomposite Drug Delivery Carriers with DARPin on Their Biodistribution and .

We present a targeted drug delivery system for therapy and diagnostics that is based on a combination of contrasting, cytotoxic, and cancer-cell-targeting properties of multifunctional carriers. The system uses multilayered polymer microcapsules loaded with magnetite and doxorubicin. Loading of magnetite nanoparticles into the polymer shell by freezing-induced loading (FIL) allowed the loading efficiency to be increased 5-fold, compared with the widely used layer-by-layer (LBL) assembly.

Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors.

Photodynamic therapy (PDT) is one of the most appealing photonic modalities for cancer treatment based on anticancer activity of light-induced photosensitizer-mediated reactive oxygen species (ROS), but a limited depth of light penetration into tissues does not make possible the treatment of deep-seated neoplasms and thus complicates its widespread clinical adoption. Here, we introduce the concept of genetically encoded bioluminescence resonance energy transfer (BRET)-activated PDT, which combines an internal light source and a photosensitizer (PS) in a single-genetic construct, which can be delivered to tumors seated at virtually unlimited depth and then triggered by the injection of a substrate to initiate their treatment. To illustrate the concept, we engineered genetic NanoLuc-miniSOG BRET pair, combining NanoLuc luciferase flashlight and phototoxic flavoprotein miniSOG, which generates ROS under luciferase-substrate injection.

Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers' Performance In Vitro and In Vivo.

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions.

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.

Barnase encapsulation into submicron porous CaCO particles: studies of loading and enzyme activity.

The present study focuses on the immobilization of the bacterial ribonuclease barnase (Bn) into submicron porous calcium carbonate (CaCO) particles. For encapsulation, we apply adsorption, freezing-induced loading and co-precipitation methods and study the effects of adsorption time, enzyme concentration and anionic polyelectrolytes on the encapsulation efficiency of Bn. We show that the use of negatively charged dextran sulfate (DS) and ribonucleic acid from yeast (RNA) increases the loading capacity (LC) of the enzyme on CaCO particles by about 3-fold as compared to the particles with Bn itself.

Antigen-Specific Stimulation and Expansion of CAR-T Cells Using Membrane Vesicles as Target Cell Surrogates.

Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery protocols are used to generate CAR-T cells.

PLGA Nanoparticles Decorated with Anti-HER2 Affibody for Targeted Delivery and Photoinduced Cell Death.

The effect of enhanced permeability and retention is often not sufficient for highly effective cancer therapy with nanoparticles, and the development of active targeted drug delivery systems based on nanoparticles is probably the main direction of modern cancer medicine. To meet the challenge, we developed polymer PLGA nanoparticles loaded with fluorescent photosensitive xanthene dye, Rose Bengal, and decorated with HER2-recognizing artificial scaffold protein, affibody Z. The obtained 170 nm PLGA nanoparticles possess both fluorescent and photosensitive properties.

Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting Magnetic Nanocarrier Delivery.

Targeted drug delivery is one of the most intriguing and challenging issues in modern biomedicine. For active targeting, full-size IgG molecules (150 kDa) are usually used. Recent studies have revealed that small artificial polypeptide scaffolds such as DARPins (14 kDa) and affibodies (8 kDa) are much more promising tools for drug delivery due to their small size, artificial nature, low immunogenicity, and many other properties.

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.

Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape.

We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins-a low immunogenic variant of exotoxin A and ribonuclease Barnase from . The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins).