Nanomaterials For Drug Delivery Research Articles

Enhanced Intracellular Delivery and Tissue Retention of Nanoparticles by Mussel-Inspired Surface Chemistry.

Nanomaterials have been broadly studied for intracellular delivery of diverse compounds for diagnosis or therapy. Currently it remains challenging for discovering new biomolecules that can prominently enhance cellular internalization and tissue retention of nanoparticles (NPs). Herein we report for the first time that a mussel-inspired engineering approach may notably promote cellular uptake and tissue retention of NPs. In this strategy, the catechol moiety is covalently anchored onto biodegradable NPs. Thus, fabricated NPs can be more effectively internalized by sensitive and multidrug resistant tumor cells, as well as some normal cells, resulting in remarkably potentiated in vitro activity when an antitumor drug is packaged. Moreover, the newly engineered NPs afford increased tissue retention post local or oral delivery. This biomimetic approach is promising for creating functional nanomaterials for drug delivery, vaccination, and cell therapy.

Safety assessment of poly(methylmethacrylate) nanomaterials for drug delivery: Genotoxicity in mammalian cells

Safety assessment of poly(methylmethacrylate) nanomaterials for drug delivery: Genotoxicity in mammalian cells

What is the role of curvature on the properties of nanomaterials for biomedical applications?

The use of nanomaterials for drug delivery and theranostics applications is a promising paradigm in nanomedicine, as it brings together the best features of nanotechnolgy, molecular biology, and medicine. To fully exploit the synergistic potential of such interdisciplinary strategy, a comprehensive description of the interactions at the interface between nanomaterials and biological systems is not only crucial, but also mandatory. Routine strategies to engineer nanomaterial-based drugs comprise modifying their surface with biocompatible and targeting ligands, in many cases resorting to modular approaches that assume additive behavior. However, emergent behavior can be observed when combining confinement and curvature. The final properties of functionalized nanomaterials become dependent not only on the properties of their constituents but also on the geometry of the nano-bio interface, and on the local molecular environment. Modularity no longer holds, and the coupling between interactions, chemical equilibrium, and molecular organization has to be directly addressed in order to design smart nanomaterials with controlled spatial functionalization envisioning optimized biomedical applications. Nanoparticle's curvature becomes an integral part of the design strategy, enabling to control and engineer the chemical and surface properties with molecular precision. Understanding how nanoparticle size, morphology, and surface chemistry are interrelated will put us one step closer to engineering nanobiomaterials capable of mimicking biological structures and their behaviors, paving the way into applications and the possibility to elucidate the use of curvature by biological systems. WIREs Nanomed Nanobiotechnol 2016, 8:334-354. doi: 10.1002/wnan.1365 For further resources related to this article, please visit the WIREs website.

Carbon Nanomaterials for Drug Delivery and Cancer Therapy.

Nanotechnology is one of the most exciting disciplines and it incorporates physics, chemistry, materials science, and biology. It can be applied to design cancer medicines with improved therapeutic indices. At the basic level, carbon nanotubes (CNTs) and graphene are sp2 carbon nanomaterials. Their unique physical and chemical properties make them interesting candidates of research in a wide range of areas including biological systems and different diseases. Recent research has been focused on exploring the potential of the CNTs as a carrier or vehicle for intracellular transport of drugs, proteins, and targeted genes in vitro and in vivo. Several research groups are actively involved to find out a functional CNT carrier capable of transporting targeted drug molecules in animal models with least toxicity. Current investigations are also focused on graphene, an allotrope of carbon, which appears to be a promising agent for successful delivery of biomolecules in various animal models. But potential clinical implementations of CNTs are still hampered by distinctive barriers such as poor bioavailability and intrinsic toxicity, which pose difficulties in tumor targeting and penetration as well as in improving therapeutic outcome. This article presents recent progresses in the design and evaluation of closely related CNTs for experimental cancer therapy and explores their implications in bringing nanomedicines into the clinics.

Development of nanotoxicology: implications for drug delivery and medical devices.

Current nanotoxicology research suffers from suboptimal in vitro models, lack of in vitro-in vivo correlations, variability within in vitro protocols, deficits in both material purity and physicochemical characterization. Reliable nanomaterial toxicity and mechanistic insights are required for health and toxicity risk assessments. Much in vitro toxicological data is inconclusive in designating whether nanomaterials for drug delivery and medical device implants are truly safe. A critique is presented to analyze the interface between toxicology and nanopharmaceuticals. Deficiencies of existing practices in toxicology are reviewed and useful emerging techniques (e.g., lab-on-a-chip, tissue engineering, atomic force microscopy, high-content analysis) are highlighted. Cross-fertilization between disciplines will aid development of biocompatible delivery and implant platforms while improvements are being suggested for better translation of nanotoxicology.

Measuring Binding Kinetics of Antibody-Conjugated Gold Nanoparticles with Intact Cells.

Antibody-conjugated nanomaterials have attracted much attention because of their applications in nanomedicine and nanotheranostics, and amplification of detection signals. For many of these applications, the nanoconjugates must bind with a cell membrane receptor (antigen) specifically before entering the cells and reaching the final target, which is thus important but not well understood. Here, a plasmonic imaging study of the binding kinetics of antibody-conjugated gold nanoparticles with antigen-expressing cells is presented, and the results are compared with that of the nanoparticle-free antibody. It is found that the nanoconjugates can significantly affect the binding kinetics compared with free antibody molecules, depending on the density of the antibody conjugated on the nanoparticles, and expressing level of the antigen on the cell membrane. The results are analyzed in terms of a transition from monovalent binding model to a bivalent binding model when the conjugation density and expressing level increase. These findings help optimize the design of functional nanomaterials for drug delivery and correct interpretation of data obtained with nanoparticle signal amplification.

Smart multifunctional drug delivery towards anticancer therapy harmonized in mesoporous nanoparticles.

Nanomedicine seeks to apply nanoscale materials for the therapy and diagnosis of diseased and damaged tissues. Recent advances in nanotechnology have made a major contribution to the development of multifunctional nanomaterials, which represents a paradigm shift from single purpose to multipurpose materials. Multifunctional nanomaterials have been proposed to enable simultaneous target imaging and on-demand delivery of therapeutic agents only to the specific site. Most advanced systems are also responsive to internal or external stimuli. This approach is particularly important for highly potent drugs (e.g. chemotherapeutics), which should be delivered in a discreet manner and interact with cells/tissues only locally. Both advances in imaging and precisely controlled and localized delivery are critically important in cancer treatment, and the use of such systems - theranostics - holds great promise to minimise side effects and boost therapeutic effectiveness of the treatment. Among others, mesoporous silica nanoparticles (MSNPs) are considered one of the most promising nanomaterials for drug delivery. Due to their unique intrinsic features, including tunable porosity and size, large surface area, structural diversity, easily modifiable chemistry and suitability for functionalization, and biocompatibility, MSNPs have been extensively utilized as multifunctional nanocarrier systems. The combination or hybridization with biomolecules, drugs, and other nanoparticles potentiated the ability of MSNPs towards multifunctionality, and even smart actions stimulated by specified signals, including pH, optical signal, redox reaction, electricity and magnetism. This paper provides a comprehensive review of the state-of-the-art of multifunctional, smart drug delivery systems centered on advanced MSNPs, with special emphasis on cancer related applications.

The Potential of Nanomaterials for Drug Delivery, Cell Tracking, and Regenerative Medicine 2014

The Potential of Nanomaterials for Drug Delivery, Cell Tracking, and Regenerative Medicine 2014

Current advances in lanthanide ion (Ln(3+))-based upconversion nanomaterials for drug delivery.

Lanthanide ion (Ln(3+))-based upconversion nano/micromaterials that emit higher-energy visible light when excited by low-energy NIR light have aroused considerable attention in the forefront of materials science and biomedical fields, which stems from their unique optical and chemical properties including minimum photodamage to living organisms, low autofluorescence, high signal-to-noise ratio and detection sensitivity, and high penetration depth in biological or environmental samples. Thus, Ln(3+)-based upconversion materials are rising new stars and are quickly emerging as potential candidates to revolutionize novel biomedical applications. In this review article, we mainly focus on the recent progress in various chemical syntheses of Ln(3+)-based upconversion nanomaterials, with special emphasis on their application in stimuli-response controlled drug release and subsequent therapy. Functional groups that are introduced into the stimuli-responsive system can respond to external triggers, such as pH, temperature, light, and even magnetic fields, which can regulate the movement of the pharmaceutical cargo and release the drug at a desired time and in a desired area. This is crucial to boost drug efficacy in cancer treatment while minimizing the side effects of cytotoxic drugs. Many multifunctional (magnetic/upconversion luminescence and porous) composite materials based on Ln(3+) have been designed for controlled drug delivery and multimodal bioimaging. Finally, the challenges and future opportunities for Ln(3+)-based upconversion materials are discussed.

Interplay of Oxidative Stress and Autophagy in PAMAM Dendrimers-Induced Neuronal Cell Death.

Poly-amidoamine (PAMAM) dendrimers are proposed to be one of the most promising drug-delivery nanomaterials. However, the toxicity of PAMAM dendrimers on the central nervous system seriously hinders their medical applications. The relationship between oxidative stress and autophagy induced by PAMAM dendrimers, and its underlying mechanism remain confusing. In this study, we reported that PAMAM dendrimers induced both reactive oxygen species and autophagy flux in neuronal cells. Interestingly, autophagy might be triggered by the formation of reactive oxygen species induced by PAMAM dendrimers. Suppression of reactive oxygen species could not only impair PAMAM dendrimers-induced autophagic effects, but also reduce PAMAM dendrimers-induced neuronal cell death. Moreover, inhibition of autophagy could protect against PAMAM dendrimers-induced neuronal cell death. These findings systematically elucidated the interplay between oxidative stress and autophagy in the neurotoxicity of PAMAM dendrimers, which might encourage the application of antioxidants and autophagy inhibitors to ameliorate the neurotoxicity of PAMAM dendrimers in clinic.

Potential of Nanomaterials as Movers and Packers for Drug Molecules

As the development of nanotechnology has extended to the world of biomolecules, a revolution has occurred in the design and assembly of nanomaterials for drug delivery with a significant potential to impact drug efficacy and patient outcomes. Currently a number of nanomaterials are under investigation for their suitability as sustained, controlled and targeted drug carriers. Leading edge of the rapidly developing nanosciences is the development and assessment of these nanomaterials, with specific physicochemical properties different from their larger/ bulk counterparts, as vehicles for transport of small and large drug molecules. The characteristics such as size, shape, chemical composition, surface structure and charge, aggregation and agglomeration, and solubility, can greatly influence interactions of these nanostructured systems or carriers with biomembranes and cells. The selectivity and reactivity achieved due to the very small size assigns these systems with a wide spectrum of applications. In this review, nanomaterials are considered in terms of the physical attributes or pharmaceutical effects allocated by them to the all-inclusive carrier or vehicle system (s). However we will limit our discussion to lipidic and polymeric nanomaterials, the two most commonly promoted, and safe nanosystems for delivery of both, the chemical or small molecular entities (SME) and the macromolecules including genes and siRNA.Contents of Paper

Surface-engineered graphene-based nanomaterials for drug delivery.

Graphene, as a newly discovered carbon allotrope, has attracted broad interest and intense attention since its discovery for both fundamental research and a vast array of industrial and biomedical applications. Considerable efforts have been devoted to understanding the nano-bio-interfaces of graphene-based materials for exploring their potential biomedical applications, including drug delivery, biosensing, biomedical imaging, stem cell technology, and photothermal therapy. This review summarizes the current studies on the physiological stability, enhanced permeability and retention (EPR) effect, active targeting and drug carrying capability of graphene-based nanomaterials, and it provides a basic understanding about the mechanisms of drug and gene delivery by these nanomaterials. Also reviewed is the recent progress on photosensitizers and theranostics using graphene-based nanomaterials. The biosafety of graphene at the cellular and animal levels is discussed. The challenges and perspectives of the field are addressed.

Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in hepatocellular carcinoma cells

Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment.

Current advances in polymer-based nanotheranostics for cancer treatment and diagnosis.

Nanotheranostics is a relatively new, fast-growing field that combines the advantages of treatment and diagnosis via a single nanoscale carrier. The ability to bundle both therapeutic and diagnostic capabilities into one package offers exciting prospects for the development of novel nanomedicine. Nanotheranostics can deliver treatment while simultaneously monitoring therapy response in real-time, thereby decreasing the potential of over- or under-dosing patients. Polymer-based nanomaterials, in particular, have been used extensively as carriers for both therapeutic and bioimaging agents and thus hold great promise for the construction of multifunctional theranostic formulations. Herein, we review recent advances in polymer-based systems for nanotheranostics, with a particular focus on their applications in cancer research. We summarize the use of polymer nanomaterials for drug delivery, gene delivery, and photodynamic therapy, combined with imaging agents for magnetic resonance imaging, radionuclide imaging, and fluorescence imaging.

Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery

Glucose-responsive materials have attracted great intention in recent years due to their potential application in drug delivery. Phenylboronic acid-containing materials have been most widely studied and used in construction of glucose-responsive system for insulin delivery. This review covers the recent advances in synthesis of phenylboronic acid-based glucose-responsive materials, especially in forms of nanogels (microgels), micelles, vesicles, and mesoporous silica nanoparticles. Applications of these nanomaterials in drug delivery are discussed.

Polymer conjugate-based nanomaterials for drug delivery.

The structure of polymeric amphiphiles with both hydrophilic and hydrophobic groups forming self-assembled nanoparticles have attracted increasing attention in studies of delivery systems of therapeutic agents. An amphiphilic carrier for self-assembly in an aqueous solution is preferable because of its structure with a hydrophobic core and hydrophilic outer shell, which can be applied to many biotechnological and pharmaceutical fields with numerous types of drugs. An amphiphilic carrier for self-assembly also represents the most appealing delivery system owing to its exceptional advantages in selectively delivering drugs to tumor cells and thus, reduction of side effects. This paper reviews two types of self-assembled nanoparticles/micelles of conjugated polymeric amphiphiles: (1) self-assembled micelles/nanoparticles of amphiphilic conjugates followed by drug loading and (2) self-assembled micelles/nanoparticles of polymer-drug conjugates where a conjugation reaction occurs between the polymer and drug. The development of the research has been addressed in this review with up-to-date references. In conclusion, the challenges and remaining difficulties for the future development are discussed.

The Potential of Nanomaterials for Drug Delivery, Cell Tracking, and Regenerative Medicine 2013

The Potential of Nanomaterials for Drug Delivery, Cell Tracking, and Regenerative Medicine 2013

Special Section Guest Editorial: Nanobiophotonics and Related Techniques

Nanobiotechnology is the convergent field of nanotechnology and biotechnology, and it has received a lot of attention in the 21st century. Typical technical fields of nanobiotechnology are the design and synthesis of biological molecules with new functionality, nanobiosensors, nanoimaging technology of cell and biosystems, and nanomaterials for drug delivery and therapy. Nanotechnology based on the structure and principle of biomaterials is the emerging field to develop new nanodevices and systems that were not possible with existing macroscale technology. It is evaluated as a core technology that can lead to new industries in the 21st century.

Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery

Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled.

In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors

Modification of drug delivery nanomaterials with affinity molecules that facilitate targeting, has rendered a new class of ligands for cell receptors, which often possess valency and dimensions different from natural counterparts. Designing strategies to target multiple receptors or, never explored, multiple epitopes on the same receptor may modulate the biodistribution properties of these nanomaterials. We examined this using antibody-directed targeting of polymer nanocarriers to transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1). Regarding epitopes on one receptor, nanocarriers addressed with anti-TfR-R17 maintained brain and lung targeting in mice, compared with “free” antibody, while anti-TfR-8D3 nanocarriers lost specificity. Coating nanocarriers with both antibodies decreased targeting in brain and liver, not lungs, modulating biodistribution. Regarding different receptors, nanocarriers coated with both anti-ICAM and anti-TfR displayed intermediate specific accumulation in lungs and higher in liver, compared to single-targeted nanocarriers, while brain targeting was comparable to TfR- and lower than ICAM-1-targeted nanocarriers. Tracing a model therapeutic cargo, acid sphingomyelinase (enzyme replacement for Niemann–Pick Disease A-B), showed that combined-targeted anti-ICAM/TfR nanocarriers enhanced enzyme delivery versus “free” enzyme, with biodistribution patterns different from single-targeted nanocarriers. Hence, targeting nanocarriers to multiple epitopes or receptors holds promise to control distribution of drug delivery nanomaterials in the body.