Responsive Nanomaterials Research Articles

Novel Reductive Responsive Chrysin-Oligomeric Hyaluronic Acid Nanomaterials to Curcumin Delivery for Cancer Therapy

Novel Reductive Responsive Chrysin-Oligomeric Hyaluronic Acid Nanomaterials to Curcumin Delivery for Cancer Therapy

Role of Oligoethylene Glycol Side Chain Length in Responsive Polymeric Nanoassemblies.

An oft-desired feature of a responsive nanomaterial is that it should undergo disassembly or morphological change upon application of a specific stimulus. The extent of response has been found to depend on factors such as the nature and the number of responsive functionalities incorporated into these particles. In this work, the length of oligoethylene glycol (OEG) side chains associated with the polymers has been shown to greatly influence the responsive behavior of polymeric nanoparticles. The integrity of these OEG-based polymeric assemblies was found to depend not only on the chemical cross-links but also on the physical cross-links in these aggregates in cases where the polymer chains bear long OEG side chains. The physical cross-linking in longer OEG side chain containing polymeric nanogels is present in the form of crystalline domains. Our results here highlight that these ethylene glycol-based hydrophilic units are not to be ignored as spectator units with water-solubilization characteristics but must be analyzed in the context of assembly stabilization and triggerability with the targeted stimulus.

Redox triggered disassembly of frame-guided assemblies

The recently reported Frame Guided Assemblies (FGA) strategy has been successfully applied to prepare assemblies with designed shapes and sizes, which exhibit good stability, providing a potential platform for drug delivery. Herein to realize controllable drug release, this work has introduced the cleavable disulfide bond into the frame, which plays important roles in both guiding and supporting the formed assemblies. It has been demonstrated that upon stimuli, the FGA vesicles could be deformed to release the loaded molecules under physiological condition, demonstrating the importance of leading hydrophobic groups. Furthermore, the disassembly of 2D frame-guided assembly system has also been realized through the same method. These responsive FGA systems may provide new nano-vehicles for intracellular drug delivery which might benefit the design of responsive nanomaterials and controllable drug delivery systems.

Stimuli-Responsive Optical Nanomaterials.

Responsive optical nanomaterials that can sense and translate various external stimuli into optical signals, in the forms of observable changes in appearance and variations in spectral line shapes, are among the most active research topics in nanooptics. They are intensively exploited within the regimes of the four classic optical phenomena-diffraction in photonic crystals, absorption of plasmonic nanostructures, as well as color-switching systems, refraction of assembled birefringent nanostructures, and emission of photoluminescent nanomaterials and molecules. Herein, a comprehensive review of these research activities regarding the fundamental principles and practical strategies is provided. Starting with an overview of their substantial developments during the latest three decades, each subtopic discussion is led with fundamental theories that delineate the correlation between nanostructures and optical properties and the delicate research strategies are elaborated with specific attention focused on working principles and optical performances. The unique advantages and inherent limitations of each responsive optical nanoscale platform are summarized, accompanied by empirical criteria that should be met and perspectives on research opportunities where the developments of next-generation responsive optical nanomaterials might be directed.

Enhanced interaction in TiO2/BiVO4 heterostructures via MXene Ti3C2-derived 2D-carbon for highly efficient visible-light photocatalysis

Heterostructured photocatalysts play a significant role in the removal of contaminants by decreasing the recombination of the photo-induced charges. Herein, we presented novel TiO2/C/BiVO4 ternary hybrids employing a 2D layered Ti3C2 MXene precursor, overcoming the lattice mismatching of TiO2/BiVO4 binary heterostructures simultaneously. Raman and XPS analyses proved the strong coupling effects of TiO2, carbon and BiVO4 components, and the heterostructures were identified from high-resolution transmission electron microscopy results. Moreover, the ternary TiO2/C/BiVO4 composites exhibit excellent photocatalytic performance of Rhodamine B degradation, which is about four times higher than pure BiVO4 and twice that of binary TiO2/BiVO4 heterostructures, reaching a reaction constant of 13.7 × 10−3 min−1 under visible-light irradiation (λ > 420 nm). In addition, for the possible mechanism for dye elimination it was proposed that RhB molecule be directly oxidized by photo-induced holes (h+) on the BiVO4 components and superoxide radical () generated from conduction band electrons of the heterostructures. This work will provide possibilities for developing visible-light responsive nanomaterials for efficient solar utilization.

Enhanced Photoacoustic and Photothermal Effect of Functionalized Polypyrrole Nanoparticles for Near-Infrared Theranostic Treatment of Tumor.

Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that thisdesigned PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.

Recent Progress on Manganese-Based Nanostructures as Responsive MRI Contrast Agents.

Manganese-based nanostructured contrast agents (CAs) entered the field of medical diagnosis through magnetic resonance imaging (MRI) some years ago. Although some of these Mn-based CAs behave as classic T1 contrast enhancers in the same way as clinical Gd-based molecules do, a new type of Mn nanomaterials have been developed to improve MRI sensitivity and potentially gather new functional information from tissues by using traditional T1 contrast enhanced MRI. These nanomaterials have been designed to respond to biological environments, mainly to pH and redox potential variations. In many cases, the differences in signal generation in these responsive Mn-based nanostructures come from intrinsic changes in the magnetic properties of Mn cations depending on their oxidation state. In other cases, no changes in the nature of Mn take place, but rather the nanomaterial as a whole responds to the change in the environment through different mechanisms, including changes in integrity and hydration state. This review focusses on the chemistry and MR performance of these responsive Mn-based nanomaterials.

External stimulus responsive inorganic nanomaterials for cancer theranostics.

Cancer is a highly intelligent system of cells, that works together with the body to thrive and subsequently overwhelm the host in order for its survival. Therefore, treatment regimens should be equally competent to outsmart these cells. Unfortunately, it is not the case with current therapeutic practices, the reason why it is still one of the most deadly adversaries and an imposing challenge to healthcare practitioners and researchers alike. With rapid nanotechnological interventions in the medical arena, the amalgamation of diagnostic and therapeutic functionalities into a single platform, theranostics provides a never before experienced hope of enhancing diagnostic accuracy and therapeutic efficiency. Additionally, the ability of these nanotheranostic agents to perform their actions on-demand, i.e. can be controlled by external stimulus such as light, magnetic field, sound waves and radiation has cemented their position as next generation anti-cancer candidates. Numerous reports exist of such stimuli-responsive theranostic nanomaterials against cancer, but few have broken through to clinical trials, let alone clinical practice. This review sheds light on the pros and cons of a few such theranostic nanomaterials, especially inorganic nanomaterials which do not require any additional chemical moieties to initiate the stimulus. The review will primarily focus on preclinical and clinical trial approved theranostic agents alone, describing their success or failure in the respective stages.

Recent Progress in 808 nm Excited Upconversion Nanomaterials as Multifunctional Nanoprobes for Visualized Theranostics in Cancers.

Near-infrared (NIR) light responsive nanomaterials have attracted considerable attention due to their location in the biological window. Especially, lanthanide-doped nanomaterials exhibit unique upconversion luminescence (UCL) properties with low background interference and long luminescence lifetime, which makes them promising in imaging diagnosis of cancers. Compared with traditional upconversion nanomaterials excited by 980 nm laser, 808 nm excitation can overcome the disadvantages of high heating effect and weak penetration depth induced by excitation source. Therefore, developing 808 nm excited upconversion nanoprobes will be important for the in vivo bio-imaging and visualized theranostics of tumors in deep-tissue. In the review paper, we systematically summarized the synthesis strategy and luminescence modulation of Nd3+-sensitized upconversion nanomaterials under 808 nm excitation, discussed the influence of excitation source on heating effect and penetration depth, and particularly focused on their applications in UCL imaging, multi-modal imaging and imaging-guided therapy of cancers.

Plasmonic carbon nanohybrids for repetitive and highly localized photothermal cancer therapy.

Integrating metallic and non-metallic platform for cancer nanomedicine is a challenging task and bringing together multi-functionality of two interfaces is a major hurdle for biomaterial design. Herein, NIR light responsive advanced hybrid plasmonic carbon nanomaterials are synthesized, and their properties toward repetitive and highly localized photothermal cancer therapy are well understood. Graphene oxide nanosheets having thickness of ∼2 nm are synthesized using modified Hummers' method, thereafter functionalized with biodegradable NIR light responsive gold deposited plasmonic polylactic-co-glycolic acid nanoshells (AuPLGA NS, tuned at 808 nm) and NIR dye (IR780) to examine their repetitive and localized therapeutic efficacy as well resulting side effects to nearby healthy cells. It is observed that AuPLGA NS decorated graphene oxide nanosheets (GO-AuPLGA) and IR780 loaded graphene oxide nanosheets (GO-IR780) are capable in standalone complete photothermal ablation of cancer cells within 4 min. of 808 nm NIR laser irradiation and also without the aid of any anticancer drugs. However, GO-AuPLGA having the potential for repetitive photothermal treatment of a big tumor, ablate the cancer cells in highly localized fashion, without having side effects on neighboring healthy cells.

Grafting Polymers from Cellulose Nanocrystals: Synthesis, Properties, and Applications

Over the past 10 years, the grafting of polymers from the surface of cellulose nanocrystals (CNCs) has gained substantial interest in both academia and industry due to the rapidly growing number of potential applications of surface-modified CNCs, which range from building blocks in nanocomposites and responsive nanomaterials to antimicrobial agents. CNCs are rod-like nanoparticles that can be isolated from renewable biosources and which exhibit high crystallinity, tunable aspect ratio, high stiffness, and strength. Upon drying, the abundance of surface hydroxyl groups often leads to a degree of irreversible aggregation, as a result of strong hydrogen bonding. Moreover, their relatively hydrophilic character renders CNCs incompatible with hydrophobic media, e.g., nonpolar solvents and polyolefin matrices. By grafting macromolecules from their surface, CNCs can be imparted with surface characteristics and other physicochemical properties that are reminiscent of the grafted polymer. This has allowed the desi...

Heating at the Nanoscale through Drug‐Delivery Devices: Fabrication and Synergic Effects in Cancer Treatment with Nanoparticles

AbstractNanocarriers for cancer therapy have been extensively studied, but there is still some research that must be addressed in order to achieve their safe application. In this field, hyperthermia thermal treatments mediated by the use of responsive nanomaterials are not different, and researchers have carried out many attempts to overcome their drawbacks due to the valuable potential of these techniques. Here, an overview is presented of nanodevices based on magnetic‐ and photoresponsive nanocrystals that respond to magnetic fields and/or near‐infrared stimuli for cancer therapies. Special attention is given to the synergic effect that can be achieved with nanoscale heating in combination with chemotherapy through drug‐delivery devices to effectively kill cancer cells. In this way, the nanoparticles act as heating sources or “hot spots,” which can trigger cellular responses in the absence of a global temperature rise, making the tumor cells more sensitive to chemotherapeutics. The fabrication of optical and magnetic drug‐delivery devices, the heating mechanisms, and their applications in tumor treatment are also summarized.

Electrostatic Screening Modulates Analyte Binding and Emission of Carbon Nanotubes

Many nanomaterials are promising biosensor elements due to capabilities for transduction of biomolecular interactions into an electrical or optical signal. Certain nanomaterials have intrinsic charges and are thus susceptible to electrostatic forces that may enhance or attenuate their response. Here, using a combination of experimental and computational approaches, we found and characterized a critical role of the solvent salt conditions in determining the extent of optical changes due to anionic analyte interaction with an intrinsically responsive nanomaterial, single-walled carbon nanotubes. Using a well-characterized model anionic analyte, we found that monovalent salts enabled greater optical changes of a polyanion-bound carbon nanotube in a highly dose-dependent manner but not with a neutrally charged analyte. Molecular dynamics simulations were used to derive a quantitative understanding of this mechanism from a free-energy perspective. We also show that salt can be used to enhance the sensitivity o...

Overcoming Ovarian Cancer Drug Resistance with a Cold Responsive Nanomaterial.

Drug resistance due to overexpression of membrane transporters in cancer cells and the existence of cancer stem cells (CSCs) is a major hurdle to effective and safe cancer chemotherapy. Nanoparticles have been explored to overcome cancer drug resistance. However, drug slowly released from nanoparticles can still be efficiently pumped out of drug-resistant cells. Here, a hybrid nanoparticle of phospholipid and polymers is developed to achieve cold-triggered burst release of encapsulated drug. With ice cooling to below ∼12 °C for both burst drug release and reduced membrane transporter activity, binding of the drug with its target in drug-resistant cells is evident, while it is minimal in the cells kept at 37 °C. Moreover, targeted drug delivery with the cold-responsive nanoparticles in combination with ice cooling not only can effectively kill drug-resistant ovarian cancer cells and their CSCs in vitro but also destroy both subcutaneous and orthotopic ovarian tumors in vivo with no evident systemic toxicity.

Metal-ion responsive reversible assembly of DNA origami dimers: G-quadruplex induced intermolecular interaction.

We present a novel metal-ion stimulated organization of DNA origami nanostructures by employing G-quadruplexes as stimuli-responsive bridges. The reversible assembly process of DNA origami was the result of conformational changes between the G-quadruplex and its single-strand state induced by monovalent cations. This study might stimulate a new design of responsive DNA-based intelligent nanomaterials.

Visible light photocatalytic activity of macro-mesoporous TiO 2 -CeO 2 inverse opals

Abstract Macro-mesoporous TiO2 inverse opal materials were synthesized and they were tested as photocatalysts under visible light irradiation. The influence of cerium oxide addition towards the Rhodamine B (RhB) photodegradation activity was evaluated. Structural, textural, spectral and surface properties of the TiO2-CeO2 inverse opal nanocomposites were studied by XRD, XPS, SEM, TEM, N2 adsorption-desorption, Diffuse Reflectance UV–vis and Photoluminescence spectroscopies. Compared to commercial TiO2 anatase, the macro-mesoporous TiO2 inverse opal exhibited six times higher kinetic rate constant in the RhB degradation under visible light irradiation. The good photocatalytic activity was related to the peculiar structure of this material, providing higher active surface area and enhancement of the mass transfer phenomena due to a very significant porosity. A positive effect of ceria addition was observed in terms of increased photocatalytic activity (73% of RhB degradation after 120 min of irradiation) when the amount of the CeO2 was low (up to 3% wt). Moreover the TiO2-3%CeO2 exhibited the lowest photoluminescence band intensity among all samples, indicating that the best efficiency in the charge carriers separation occurs in this catalyst. The presence of Ce3+ species was favoured for small amounts of cerium oxide, resulting in a positive effect on the photoactivity. The mutual interaction between Ti and Ce metal cations promotes an easier charge transfer on the surface, accelerating in particular the Ce4+/Ce3+ redox process that is beneficial for the oxidation reactions. On the contrary the use of high amounts of cerium oxide (>5% wt) led to a progressive agglomeration of CeO2, thus increasing the crystal size of TiO2-CeO2 particles (from 27 to 33 nm) and favouring the coverage of TiO2 active sites. This work reports the preparation and some photoactivity tests of some visible light responsive nanomaterials for an efficient solar energy utilization.

Smart Self-Assembled Organic Nanoprobe for Protein-Specific Detection: Design, Synthesis, Application, and Mechanism Studies.

Specific detection or imaging protein has high potential to contribute greatly to medical diagnosis, biological research, and therapeutic applications. The level of human serum albumin (HSA) in blood is related to a variety of diseases and thus serves as an important biomarker for fast clinical diagnosis. Here we report the use of aggregation-induced emission (AIE) based supramolecular assembly to design biomolecular responsive smart organic nanomaterials for detection protein HSA. The designed nanoprobes were aggregates of small molecules and silent in fluorescence, but in the presence of HSA they disassembled and produced a clear turn-on fluorescent signal. Of a small library of nanoprobes constructed for HSA detection, structure-optical signaling and screening studies revealed that nanoprobe 7 is the most efficient one. Mechanism studies showed that nanoprobe 7 was bonded with Site I of HSA through the multiple noncovalent interactions. The resultant restriction of intramolecular rotation of nanoprobe 7 in the hydrophobic cavity of HSA induced fluorescent emission, which was validated by competitive binding assays and molecular docking. More importantly, nanoprobe 7 was successfully applied to recognize and quantify HSA in human serum samples. This study demonstrates nanoprobe 7 is a promising tool for clinical real and fast detection of HSA and thus may find many applications, and the molecular assembly based on AIE also opens a new avenue for designing smart nanomaterials for the sensitive and selective detection for varied analytes.

Lipogels responsive to near-infrared light for the triggered release of therapeutic agents

Hydrogels composed of fibrin embedding nanoparticles responsive to near infrared (NIR) energy and thermosensitive liposomes loaded with doxorubicin hydrochloride (DOX), were prepared by in situ polymerization. NIR-light irradiation of these constructs, referred to as "NIR responsive lipogels", results in the controlled release of DOX to the surrounding medium. This technology may use fully degradable components and can preserve the bioactivity of liposomal cargo after remote triggering to finely regulate the dose and bioavailability of delivered payloads. NIR responsive lipogels technology overcomes the limitations of drug release systems based on the combination of liposomes and degradable polymeric materials, which in many cases lead to insufficient release at therapy onset or to overdose during high degradation period.

Near infrared light-controlled therapeutic molecules release of nanocarriers in cancer therapy

Spurred by the development in materials chemistry, stimuli-responsive nanocarriers that could show sharp responses to various environmental changes have found applications in many fields including controlled drug delivery in the past few years. Among all the available stimuli, light has recently attracted much attention owing to their non-invasiveness and the possibility of remote spatiotemporal control. A large amount of photoresponsive systems have been constructed to achieve on-demand drug, gene or other kinds of cytotoxic species release in responsive to illumination of a specific wavelength in near-infrared region (NIR), which shows better tissue penetration compared to visible or ultraviolet (UV) light with shorter wavelengths. Exploration of NIR light-responsive therapeutic cargoes delivery systems opens up a new and exciting possibility for applications in nanomedicine. In this review article, we mainly focus on the recent progress in nanocarriers with different kinds of strategies to achieve NIR light-based control over the delivery process, with special emphasis on their application in NIR photo-response controlled therapeutic cargoes release and subsequent therapy. The final section reviews current challenges in the use of NIR responsive nanomaterials and potential solutions.

Comparing Effects of Redox Sensitivity of Organic Nanoparticles to Photodynamic Activity

Smart responsive nanomaterials, which are sensitive to biological signals, are promising therapeutic formulations. It has been well studied that redox potential is much different at both tissue and cellular level. In this work, three organic nanoparticles with variable redox sensitivity were fabricated, and their redox sensitivity was evaluated and compared in detail. First, diselenide, disulfide, and carbon–carbon bond containing porphyrin dimers TPP-SeSe/TPP-SS/TPP-CC were synthesized. Then, the corresponding self-assembled nanoparticles (TPP-SeSe/TPP-SS/TPP-CC NPs) were prepared via nanoprecipitation method. As-synthesized nanoparticles were utilized to systematically compare the stimuli responsiveness to reductive agents (e.g., glutathione) in different conditions, especially in the living cells, through the singlet oxygen generation ability and the cytotoxicity. A series of experimental results demonstrated that the diselenide bond shows better superiority in reduction sensitivity than that of the di...