Synthesis and characterization of Fe3O4@SiO2@PDA@Ag core-shell nanoparticles and biological application on human lung cancer cell line and antibacterial strains.

Novel magnetic and metallic nanoparticles garner much attention of researchers due to their biological, chemical and catalytic properties in many chemical reactions. In this study, we have successfully prepared a core-shell Fe3O4@SiO2@PDA nanocomposite wrapped with Ag using a simple synthesis method, characterised and tested on small cell lung cancer and antibacterial strains. Incorporating Ag in Fe3O4@SiO2@PDA provides promising advantages in biomedical applications. The magnetic Fe3O4 nanoparticles were coated with SiO2 to obtain negatively charged surface which is then coated with polydopamine (PDA). Then silver nanoparticles were assembled on Fe3O4@SiO2@PDA surface, which results in the formation core-shell nanocomposite. The synthesised nanocomposite were characterized using SEM-EDAX, dynamic light scattering, XRD, FT-IR and TEM. In this work, we report the anticancer activity of silver nanoparticles against H1299 lung cancer cell line using MTT assay. The cytotoxicity data revealed that the IC50 of Fe3O4@SiO2@PDA@Ag against H1299 lung cancer nanocomposites cells was 21.52 µg/mL. Furthermore, the biological data of nanocomposites against Gram-negative 'Pseudomonas aeruginosa' and Gram-positive 'Staphylococcus aureus' were carried out. The range of minimum inhibitory concentration was found to be 115 µg/mL where gentamicin was used as a standard drug. The synthesized AgNPs proves its supremacy as an efficient biomedical agent and AgNPs may act as potential beneficial molecule in lung cancer chemoprevention and antibacterial strains.

In the present study, we have successfully prepared a core-shell Fe₃O₄@SiO₂@PDA@Ag nanocomposite.We have investigated the dose-dependent cellular toxicity of silver nanocomposite in the nonsmall cell lung cancer cell line H1299 using MTT assay.Also, we have evaluated the mode of cell death using apoptosis.We have also evaluated the bioactivity of AgNPs on both Gram-positive and Gram-negative bacterial cells with highly efficient antibacterial potency.

Nanoparticles for combined photo- and chemo-dynamic therapy of cancer cells involving endogenous glutathione depletion.

Background: Reactive oxygen species (ROS) are powerful weapons for various anticancer therapies. However, high glutathione (GSH) levels in cancer cells can significantly reduce the efficacy of such therapies. Methods: In this study, pH-responsive fluorescein-encapsulated zeolitic imidazolate framework-8 nanoparticles were synthesized for ROS-mediated combination therapy. Results: Upon blue light activation, fluorescein displayed a high singlet oxygen photogeneration ability for photodynamic therapy. Concurrently, accumulated Zn2+ from degraded zeolitic imidazolate framework-8 stimulated simultaneous ROS generation and GSH depletion, thereby successfully inducing chemodynamic therapy. This triggered a cascade of photo-physical and chemical processes culminating in the localized generation of ROS, ultimately breaking the intracellular redox equilibrium. Conclusion: This nanoformulation can potentially be used for light-activated ROS-mediated therapy for the management of superficial tumors.

Highly reactive molecules called reactive oxygen species (ROS) are known to be present in excess in cancer cells. As a result, cancer cells are more susceptible to death by any further rise in levels of these species. In the current study, fluorescein-encapsulated zeolitic imidazolate nanoparticles were prepared for blue light-activated ROS-enhancing combination therapy. The nanoparticles displayed significant toxicity against a breast cancer cell line and simultaneously induced glutathione depletion, an antioxidant known to reduce the efficacy of various cancer therapies. Thus, this study reveals the potential of fluorescein-encapsulated zeolitic imidazolate nanoparticles for light-activated ROS-mediated therapy for the treatment of superficial tumors.

Lipid-Based Inhalable Micro- and Nanocarriers of Active Agents for Treating Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) afflicts about 2 million people worldwide, with both genetic (familial) and environmental factors contributing to its development and spread. The inadequacy of currently available therapeutic techniques, such as surgery, chemotherapy, and radiation therapy, in addressing NSCLC is reflected in the very low survival rate of this disease. Therefore, newer approaches and combination therapy regimens are required to reverse this dismal scenario. Direct administration of inhalable nanotherapeutic agents to the cancer sites can potentially lead to optimal drug use, negligible side effects, and high therapeutic gain. Lipid-based nanoparticles are ideal agents for inhalable delivery owing to their high drug loading, ideal physical traits, sustained drug release, and biocompatibility. Drugs loaded within several lipid-based nanoformulations, such as liposomes, solid-lipid nanoparticles, lipid-based micelles, etc., have been developed as both aqueous dispersed formulations as well as dry-powder formulations for inhalable delivery in NSCLC models in vitro and in vivo. This review chronicles such developments and charts the future prospects of such nanoformulations in the treatment of NSCLC.

Comparative analysis of cobalt ferrite and iron oxide nanoparticles using bimodal hyperthermia, along with physical and in silico interaction with human hemoglobin.

Magnetic nanoparticles (MNPs) have captivated the scientific community towards biomedical applications owing to their numerous distinctive physio-chemical properties. In this work, cobalt ferrite (CFNPs) and iron oxide nanoparticles (IONPs) were synthesized using the thermal decomposition method and then functionalized with polyacrylic acid (PAA) for aqueous dispersion. Associated techniques, namely TEM, FESEM, DLS, XRD, and VSM, were used to characterize the synthesized nanoparticles. We also investigated the light-induced and magnetic-field-induced hyperthermia properties of the PAA-functionalized MNPs. It was found that the PAA-CFNPs show a high specific absorption rate (SAR) compared with the PAA-IONPs. Since blood plasma is essential for the delivery and targeting of drugs, studying biological interactions is crucial for effective therapeutic use. Therefore, we performed physical and in silico studies to probe into the mechanistic interaction of CFNPs and IONPs with human hemoglobin. From these studies, we inferred the successful binding between the nanoparticles and protein. Preliminary in vitro cytocompatibility and photothermal toxicity studies in breast cancer (MCF-7) cells treated with the nanoparticles revealed a low dark toxicity and significant laser-induced photothermal toxicity.

Emerging Prospects of Nanozymes for Antibacterial and Anticancer Applications.

The ability of some nanoparticles to mimic the activity of certain enzymes paves the way for several attractive biomedical applications which bolster the already impressive arsenal of nanomaterials to combat deadly diseases. A key feature of such 'nanozymes' is the duplication of activities of enzymes or classes of enzymes, such as catalase, superoxide dismutase, oxidase, and peroxidase which are known to modulate the oxidative balance of treated cells for facilitating a particular biological process such as cellular apoptosis. Several nanoparticles that include those of metals, metal oxides/sulfides, metal-organic frameworks, carbon-based materials, etc., have shown the ability to behave as one or more of such enzymes. As compared to natural enzymes, these artificial nanozymes are safer, less expensive, and more stable. Moreover, their catalytic activity can be tuned by changing their size, shape, surface properties, etc. In addition, they can also be engineered to demonstrate additional features, such as photoactivated hyperthermia, or be loaded with active agents for multimodal action. Several researchers have explored the nanozyme-mediated oxidative modulation for therapeutic purposes, often in combination with other diagnostic and/or therapeutic modalities, using a single probe. It has been observed that such synergistic action can effectively by-pass the various defense mechanisms adapted by rogue cells such as hypoxia, evasion of immuno-recognition, drug-rejection, etc. The emerging prospects of using several such nanoparticle platforms for the treatment of bacterial infections/diseases and cancer, along with various related challenges and opportunities, are discussed in this review.

Transforming Nuclear Medicine with Nanoradiopharmaceuticals.

Nuclear medicine is expected to make major advances in cancer diagnosis and therapy; tumor-targeted radiopharmaceuticals preferentially eradicate tumors while causing minimal damage to healthy tissues. The current scope of nuclear medicine can be significantly expanded by integration with nanomedicine, which utilizes nanoparticles for cancer diagnosis and therapy by capitalizing on the increased surface area-to-volume ratio, the passive/active targeting ability and high loading capacity, the greater interaction cross section with biological tissues, the rich surface properties of nanomaterials, the facile decoration of nanomaterials with a plethora of functionalities, and the potential for multiplexing several functionalities within one construct. This review provides a comprehensive discussion of nuclear nanomedicine using tumor-targeted nanoparticles for cancer radiation therapy with either pre-embedded radionuclides or nonradioactive materials which can be extrinsically triggered using various external nuclear particle sources to produce in situ radioactivity. In addition, it describes the prospect of combining nuclear nanomedicine with other modalities to enable synergistically enhanced combination therapies. The review also discusses advances in the fabrication of radionuclides as well as describes laser ablation technologies for producing nanoradiopharmaceuticals, which combine the ease of production with exceptional purity and rapid biodegradability, along with additional imaging or therapeutic functionalities. From a practical standpoint, these attributes of nanoradiopharmaceuticals may provide distinct advantages in diagnostic/therapeutic sensitivity and specificity, imaging resolution, and scalability of turnkey platforms. Coupling image-guided targeted radiation therapy with the possibility of in situ activation of nanomaterials as well as combining with other therapeutic modalities using a multifunctional nanoplatform could herald an era of exciting technological and therapeutic advances to radically transform the landscape of nuclear medicine. The review concludes with a discussion of current challenges and presents the authors' views on future opportunities to stimulate further research in this rewarding field of high societal impact.

Iron Oxide-Based Magneto-Optical Nanocomposites for In Vivo Biomedical Applications.

Iron oxide nanoparticles (IONPs) have played a pivotal role in the development of nanomedicine owing to their versatile functions at the nanoscale, which facilitates targeted delivery, high contrast imaging, and on-demand therapy. Some biomedical inadequacies of IONPs on their own, such as the poor resolution of IONP-based Magnetic Resonance Imaging (MRI), can be overcome by co-incorporating optical probes onto them, which can be either molecule- or nanoparticulate-based. Optical probe incorporated IONPs, together with two prominent non-ionizing radiation sources (i.e., magnetic field and light), enable a myriad of biomedical applications from early detection to targeted treatment of various diseases. In this context, many research articles are in the public domain on magneto-optical nanoparticles; discussed in detail are fabrication strategies for their application in the biomedical field; however, lacking is a comprehensive review on real-life applications in vivo, their toxicity, and the prospect of bench-to-bedside clinical studies. Therefore, in this review, we focused on selecting such important nanocomposites where IONPs become the magnetic component, conjugated with various types of optical probes; we clearly classified them into class 1 to class 6 categories and present only in vivo studies. In addition, we briefly discuss the potential toxicity of such nanocomposites and their respective challenges for clinical translations.

Targeting nonapoptotic pathways with functionalized nanoparticles for cancer therapy: current and future perspectives.

Apoptotic death evasion is a hallmark of cancer progression. In this context, past decades have witnessed cytotoxic agents targeting apoptosis. However, owing to cellular defects in the apoptotic machinery, tumors develop resistance to apoptosis-based cancer therapies. Hence, targeting nonapoptotic cell-death pathways displays enhanced therapeutic success in apoptosis-defective tumor cells. Exploitation of multifunctional properties of engineered nanoparticles may allow cancer therapeutics to target yet unexplored pathways such as ferroptosis, autophagy and necroptosis. Necroptosis presents a programmed necrotic death initiated by same apoptotic death signals that are caspase independent, whereas autophagy is self-degradative causing vacuolation, and ferroptosis is an iron-dependent form driven by lipid peroxidation. Targeting these tightly regulated nonapoptotic pathways may emerge as a new direction in cancer drug development, diagnostics and novel cancer nanotherapeutics. This review highlights the current challenges along with the advancement in this field of research and finally summarizes the future perspective in terms of their clinical merits.

Iron oxide nanoparticles conjugated with organic optical probes for in vivo diagnostic and therapeutic applications.

The role and scope of functional inorganic nanoparticles in biomedical research is well established. Among these, iron oxide nanoparticles (IONPs) have gained maximum attention as they can provide targeting, imaging and therapeutic capabilities. Furthermore, incorporation of organic optical probes with IONPs can significantly enhance the scope and viability of their biomedical applications. Combination of two or more such applications renders multimodality in nanoparticles, which can be exploited to obtain synergistic benefits in disease detection and therapy viz theranostics, which is a key trait of nanoparticles for advanced biomedical applications. This review focuses on the use of IONPs conjugated with organic optical probe/s for multimodal diagnostic and therapeutic applications in vivo.

Fluorescein-entrapped magnetosomes for magnetically assisted photodynamic therapy.

Aim: We investigated the application of fluorescein (FL)-entrapped magnetosomes, in other words, silica-coated iron oxide nanoparticles entrapped within niosomes (SIO/NIO), in magnetically assisted photodynamic therapy (PDT) in vitro. Methods: Panc-1 cells were treated with the magnetosomes, with and without external magnetic guidance, and irradiated with blue light. Results & conclusion: Upon photoactivation, the FL-entrapped magnetosomes can produce higher singlet oxygen in comparison to FL-entrapped micelles, probably due to the higher release tendency of the photosensitizer from the former. In vitro studies in Panc-1 cells revealed magnetically assisted enhancement in the cellular uptake of the magnetosomes. Magnetic assistance also led to enhancement in PDT efficiency in cells treated with the FL-entrapped magnetosomes and light, thus highlighting their potential in PDT.

UCNP-based Photoluminescent Nanomedicines for Targeted Imaging and Theranostics of Cancer.

Theranostic approach is currently among the fastest growing trends in cancer treatment. It implies the creation of multifunctional agents for simultaneous precise diagnosis and targeted impact on tumor cells. A new type of theranostic complexes was created based on NaYF4: Yb,Tm upconversion nanoparticles coated with polyethylene glycol and functionalized with the HER2-specific recombinant targeted toxin DARPin-LoPE. The obtained agents bind to HER2-overexpressing human breast adenocarcinoma cells and demonstrate selective cytotoxicity against this type of cancer cells. Using fluorescent human breast adenocarcinoma xenograft models, the possibility of intravital visualization of the UCNP-based complexes biodistribution and accumulation in tumor was demonstrated.

Robust dual modality antibacterial action using silver-Prussian blue nanoscale coordination polymer.

We report the synthesis of novel silver-doped Prussian blue nanoscale coordination polymers (SPB NCPs), for dual modality photothermal ablation and oxidative toxicity in bacterial cells. The comparison of SPB NCPs (having Fe-CN-Ag bonds) with the conventionally used Prussian blue nanoscale coordination polymers (PB NCPs, having Fe-CN-Fe bonds) was investigated in terms of their physical and therapeutic properties. It was observed that both PB and SPB NCPs have similar physical dimensions, crystalline phase and optical properties. Both these NCPs showed robust photothermal effect by heat generation (hyperthermia) upon exposure to red laser light. However, among the two, only SPB NCP showed oxidase-like activity by generating H2O2 in aqueous medium, presumably due to its silver content. In vitro antibacterial studies revealed that the SPB NCPs, but not PB NCPs, show inherent toxicity towards bacteria with an IC50 value close to 2.5 µg/ml. It can be inferred that this toxicity is oxidative in nature, as a result of the oxidase-like behaviour shown by SPB NCPs. Furthermore, light activation resulted in substantial additional antibacterial effect (photothermal toxicity) in bacterial cells treated with SPB NCPs. In comparison, marginal additional photothermal toxicity was observed in PB NCP-treated bacteria. Thus, we conclude that the combination of dual modality oxidative and photothermal toxicities demonstrated by SPB NCPs, but not by control PB NCPs, makes the former promising antibacterial agents at low dosages.

Gold Nanoparticle-Enhanced Photodynamic Therapy from Photosensitiser-Entrapped Ormosil Nanoparticles.

Herein, we investigate the effect of the surface attachment of gold nanoparticles (AuNPs) on photosensitiser-entrapped organically modified silica (ormosil) nanoparticles for enhanced photodynamic therapy (PDT). Photosensitiser methylene blue (MB)-entrapped ormosil nanoparticles of three different diameters (30/55/80 nm) were synthesised, and AuNPs were attached to their surface. Subsequent light irradiation with a 630 nm laser resulted in the production of singlet oxygen (1O2), with different amounts depending on the diameter of the ormosil nanoparticle. Enhancement in 1O2 production was observed upon the AuNP attachment on the ormosil surface. In vitro studies in pancreatic cancer (Panc-1) cells have demonstrated that cellular uptake and photodynamic cytotoxicity are also dependent on the size of ormosil nanoparticles and AuNP attachment. These studies pave the way for designing ormosil nanoparticles with suitable size and surface attachment for PDT applications.

Copper-Gallic Acid Nanoscale Metal-Organic Framework for Combined Drug Delivery and Photodynamic Therapy.

In this paper, we report the synthesis of bioactive copper-gallic acid nanoscale metal-organic framework for the codelivery of anticancer agent (gallic acid) and photosensitizer (methylene blue) to cancer cells. A supramolecular coordination complex of copper-bioactive frameworks (bio MOFs) were employed as the carrier of two anticancer agents. The first one is the natural phenolic acid (gallic acid), which forms a part of the framework structure (building block). The other one is the photosensitizer methylene blue, loaded as a guest molecule within the amphiphilic pores of the framework. In vitro cytotoxicity and in vivo tumor regression assays revealed enhanced cytotoxicity of dual drug nanoframework when compared with the equivalent dosages of free drugs in the presence of light.

Doxorubicin-loaded casein nanoparticles for drug delivery: Preparation, characterization and in vitro evaluation.

Casein, a milk protein that self-assembles to form micelles in aqueous solution, can bind to a wide range of drugs (hydrophilic and hydrophobic). Herein, a low cost and facile method was reported to prepare casein nanoparticles loaded with an anticancer drug, doxorubicin (DOX). The particles were fabricated by adding an excess of Ca2+ ions which brings the soluble casein present in the solution into the micellar framework to form dense nanoparticles. The binding between the drug and the macromolecule was confirmed using fluorescence studies. Circular Dichroism (CD) shows that upon addition of excess Ca2+ the protein chains rearrange. The nanoparticles were characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and dynamic light scattering (DLS). The release at pH 1 was higher than the physiological pH making this formulation potent for delivering the drug to the stomach via the oral route. The DOX attached with casein showed improved efficacy, i.e., better cytotoxicity against human pancreatic carcinoma cell line, PANC 1 cells as compared to the free drug of the same concentration, owing to higher cell uptake of the macromolecule.

Iron oxide-doped niosomes as drug carriers for magnetically targeted drug delivery.

Magnetism has wide applications in various fields, such as diagnostics, drug targeting, molecular biology, cell isolation, cell purification, hyperthermia, and radioimmunoassay. In this study, we synthesized niosomes doped with iron oxide nanoparticles and a fluorophore for potential applications in magnetically targeted drug delivery. Release kinetics of the fluorophore and cytotoxicity were assessed. The results demonstrate that niosomes doped with iron oxide nanoparticles can serve as proficient and effective drug carriers in magnetically targeted drug delivery.

Preparation and characterization of superparamagnetic iron oxide nanoparticles for magnetically guided drug delivery.

Iron oxide nanoparticles have unique magnetic properties and therefore readily respond to applied magnetic fields. Moreover, their surfaces can be used to attach active molecules via various covalent or noncovalent interactions. Thus, they can be used as drug carriers for magnetically controlled delivery to specific biological sites of interest. In the present study, we have synthesized aqueous dispersed samples of citric acid-capped iron oxide nanoparticles, and the anticancer drug doxorubicin was then linked with these superparamagnetic iron oxide nanoparticles via a simple noncovalent interaction. Our results show that the conjugated drug releases from the nanoparticles in a sustained manner. The cellular uptake of these nanoparticles was found to be substantial, although it can be further enhanced using magnetic guidance. These nanoparticles (drug free) were found to be nontoxic to cells; however, upon drug conjugation, drug-induced toxicity was observed, owing to the slow release of drug from the nanoparticles.

Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.

The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease.

Organically modified titania nanoparticles for sustained drug release applications.

In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications.

Optimizing the synthesis of red- and near-infrared CuInS2 and AgInS2 semiconductor nanocrystals for bioimaging.

This work reports the study of optimization of the reaction parameters on the synthesis of high quality CuInS2 and AgInS2 nanocrystals for bioimaging applications. The concentration of reaction precursors (e.g. Ag, Cu, In and S) plays a key role in determining the emission profile of these ternary quantum dots (QDs). By carefully varying the precursor compositions, the emission of QD can be tuned from red to near infrared (NIR) region. Taking the advantages of NIR emission, which possesses minimal absorption in biological tissues, we have also prepared water-dispersible CuInS2/ZnS and AgInS2/ZnS nanocrystals and demonstrated the high biocompatibility for both deep tissue penetration and tumor targeting. The QDs were stabilized in Pluronic F127 block copolymer micelles, offering us optically and colloidally stable contrast agents for in vitro and in vivo imaging. Two-photon excitation of QD has also been demonstrated, accomplishing a NIR-to-NIR transaction. This study devotes the key steps in promoting the use of ternary QDs as low-toxic, photostable, and cadmium-free semiconductor nanocrystal formulation for multiple imaging applications.