Search

Tumors remain one of the major threats to public health and there is an urgent need to design new pharmaceutical agents for their diagnosis and treatment. In recent years, due to the rapid development of nanotechnology, biotechnology, catalytic science, and theoretical computing, subtlety has gradually made great progress in research related to tumor diagnosis and treatment. Compared to conventional drugs, enzymes can improve drug distribution and enhance drug enrichment at the tumor site, thereby reducing drug side effects and enhancing drug efficacy. Nanozymes can also be used as tumor tracking imaging agents to reshape the tumor microenvironment, providing a versatile platform for the diagnosis and treatment of malignancies. In this paper, we review the current status of research on enzymes in oncology and analyze novel oncology therapeutic approaches and related mechanisms. To date, a large number of nanomaterials, such as noble metal nanomaterials, nonmetallic nanomaterials, and carbon-based nanomaterials, have been shown to be able to function like natural enzymes, particularly with significant advantages in tumor therapy. In light of this, the authors in this review have systematically summarized and evaluated the construction, enzymatic activity, and their characteristics of nanozymes with respect to current modalities of tumor treatment. In addition, the application and research progress of different types of nicknames and their features in recent years are summarized in detail. We conclude with a summary and outlook on the study of nanozymes in tumor diagnosis and treatment. It is hoped that this review will inspire researchers in the fields of nanotechnology, chemistry, biology, materials science and theoretical computing, and contribute to the development of nano-enzymology. The mechanism and classification, systematically evaluated construction, enzymatic activity, and characteristics of nanoenzymes is discussed with respect to current modalities of tumor treatment. [Display omitted] • The mechanism and classification of nanozymes in tumor therapy are summarized and described their advantages. • Systematically evaluate construction, enzymatic activity, and properties of nanozymes in current modalities of tumor treatment. • The current states, challenges, and some perspectives for nanoeymes in tumor diagnosis and treatment are discussed. [ABSTRACT FROM AUTHOR]

For early-stage breast cancers mastectomy is an aggressive form of treatment. Therefore, there is a need for new treatment strategies that can enhance the use of lumpectomy by eliminating residual cancer cells with limited side effects to reduce local recurrence. Although, various radiotherapy-based methods have been developed, residual cells are found in 20–55% of the time at the first operation. Furthermore, some current treatment methods result in poor cosmesis. For the last decade, the authors have been exploring the use of polymeric composite materials in single and multi-modal implantable biomedical devices for post-operative treatment of breast cancer. In this paper, the concept and working principles of the devices, as well as selected results from experimental and numerical investigations, are presented. The results show the potential of the biomedical implants for cancer treatment. [ABSTRACT FROM AUTHOR]

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments. [ABSTRACT FROM AUTHOR]

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. [ABSTRACT FROM AUTHOR]

In this paper, we describe the effects of the combination of topographical, mechanical, chemical and intracellular electrical stimuli on a co-culture of fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown onto an engineered micro-grooved (10 µm-wide grooves) polyacrylamide substrate, showing a precisely tuned Young’s modulus (∼ 14 kPa) and a small thickness (∼ 12 µm). We enhanced the co-culture properties through intracellular stimulation produced by piezoelectric nanostructures (i.e., boron nitride nanotubes) activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes to convert outer mechanical waves (such as ultrasounds) in intracellular electrical stimuli, by exploiting the direct piezoelectric effect. We demonstrated that nanotubes were internalized by muscle cells and localized in both early and late endosomes, while they were not internalized by the underneath fibroblast layer. Muscle cell differentiation benefited from the synergic combination of topographical, mechanical, chemical and nanoparticle-based stimuli, showing good myotube development and alignment towards a preferential direction, as well as high expression of genes encoding key proteins for muscle contraction (i.e., actin and myosin). We also clarified the possible role of fibroblasts in this process, highlighting their response to the above mentioned physical stimuli in terms of gene expression and cytokine production. Finally, calcium imaging-based experiments demonstrated a higher functionality of the stimulated co-cultures. [ABSTRACT FROM AUTHOR]

In this paper we show that hydroxyapatite nanoparticles (NP) can not only act as a chaperon (by imparting thermostability) but can serve as a synthetic enhancer of activity of an isolated extracellular pectate lyase (APL) with low native state activity. The purified enzyme (an attenuated strain of Macrophomina phaseolina) showed feeble activity at 50°C and pH 5.6. However, on addition of 10.5 µg/ml of hydroxyapatite nanoparticles (NP), APL activity increased 27.7 fold with a 51 fold increase in half-life at a temperature of 90°C as compared to untreated APL. The chaperon like activity of NP was evident from entropy–enthalpy compensation profile of APL. The upper critical temperature for such compensation was elevated from 50°C to 90°C in presence of NP. This dual role of NP in enhancing activity and conferring thermostability to a functionally impaired enzyme is reported for the first time. [ABSTRACT FROM AUTHOR]

Cationic polymers such as poly(amidoamine), PAMAM, dendrimers have been used to electrostatically complex siRNA molecules forming dendriplexes for enhancing the cytoplasmic delivery of the encapsulated cargo. However, excess PAMAM dendrimers is typically used to protect the loaded siRNA against enzymatic attack, which results in systemic toxicity that hinders the in vivo use of these particles. In this paper, we evaluate the ability of G4 (flexible) and G5 (rigid) dendrimers to complex model siRNA molecules at low +/− ratio of 2/1 upon incubation for 20 minutes and 24 hours. We examine the ability of the formed G4 and G5 dendriplexes to shield the loaded siRNA molecules and protect them from degradation by RNase V1 enzymes using atomic force microscopy (AFM). Results show that G4 and G5 dendrimers form similar hexagonal complexes upon incubation with siRNA molecules for 20 minutes with average full width of 43±19.3 nm and 62±8.3 at half the maximum height, respectively. AFM images show that these G4 and G5 dendriplexes were attacked by RNase V1 enzyme leading to degradation of the exposed RNA molecules that increased with the increase in incubation time. In comparison, incubating G4 and G5 dendrimers with siRNA for 24 hours led to the formation of large particles with average full width of 263±60 nm and 48.3±2.5 nm at half the maximum height, respectively. Both G4 and G5 dendriplexes had a dense central core that proved to shield the loaded RNA molecules from enzymatic attack for up to 60 minutes. These results show the feasibility of formulating G4 and G5 dendriplexes at a low N/P (+/−) ratio that can resist degradation by RNase enzymes, which reduces the risk of inducing non-specific toxicity when used in vivo. [ABSTRACT FROM AUTHOR]

Biogenetic silica displays intricate patterns assembling from nano- to microsize level and interesting non-spherical structures differentiating in specific directions. Several model systems have been proposed to explain the formation of biosilica nanostructures. Of them, phase separation based on the physicochemical properties of organic amines was considered to be responsible for the pattern formation of biosilica. In this paper, using tetraethyl orthosilicate (TEOS, Si(OCH2CH3)4) as silica precursor, phospholipid (PL) and dodecylamine (DA) were introduced to initiate phase separation of organic components and influence silica precipitation. Morphology, structure and composition of the mineralized products were characterized using a range of techniques including field emission scanning electron microscopy (FESEM), transmission electron microscope (TEM), X-ray diffraction (XRD), thermogravimetric and differential thermal analysis (TG-DTA), infrared spectra (IR), and nitrogen physisorption. The results demonstrate that the phase separation process of the organic components leads to the formation of asymmetrically non-spherical silica structures, and the aspect ratios of the asymmetrical structures can be well controlled by varying the concentration of PL and DA. On the basis of the time-dependent experiments, a tentative mechanism is also proposed to illustrate the asymmetrical morphogenesis. Therefore, our results imply that in addition to explaining the hierarchical porous nanopatterning of biosilica, the phase separation process may also be responsible for the growth differentiation of siliceous structures in specific directions. Because organic amine (e.g., long-chair polyamines), phospholipids (e.g., silicalemma) and the phase separation process are associated with the biosilicification of diatoms, our results may provide a new insight into the mechanism of biosilicification. [ABSTRACT FROM AUTHOR]