The translocation of nanomaterials or complex delivery systems into the cytosol is a major challenge in nanobiotechnology. After receptor‐mediated endocytosis, most nanomaterials are sequestered and ...undergo degradation, therapy inactivation, or exocytosis. Herein we explore a novel surface particle coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell‐invasive mechanisms, namely, receptor‐mediated endocytosis, endolysosomal escape, and cytosolic particle release preserving cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical, or catalytic functionalities, thus opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting new developments in the biotechnological, pharmaceutical, and biomedical industries.
A clean getaway: An engineered nanocoating composed of carbon nanotubes enabled particles with nano/micrometer dimensions to break through lysosomal membranes and invade the intracellular realm (see picture). The coated materials resemble viruses in terms of their structure and reproduce the viral cell‐invasive mechanisms of receptor‐mediated endocytosis, endolysosomal escape, and cytosolic particle release with the preservation of cell viability.
Glioblastoma multiforme (GBM) is a devastating tumor of the central nervous system, currently missing an effective treatment. The therapeutic gold standard consists of surgical resection followed by ...chemotherapy (usually with temozolomide, TMZ) and/or radiotherapy. TMZ does not, however, provide significant survival benefit after completion of treatment because of development of chemoresistance and of heavy side effects of systemic administration. Improvement of conventional treatments and complementary therapies are urgently needed to increase patient survival and quality of life. Stimuli-responsive lipid-based drug delivery systems offer promising prospects to overcome the limitations of the current treatments. In this work, multifunctional lipid-based magnetic nanovectors functionalized with the peptide angiopep-2 and loaded with TMZ (Ang-TMZ-LMNVs) were tested to enhance specific GBM therapy on an in vivo model. Exposure to alternating magnetic fields (AMFs) enabled magnetic hyperthermia to be performed, that works in synergy with the chemotherapeutic agent. Studies on orthotopic human U-87 MG-Luc2 tumors in nude mice have shown that Ang-TMZ-LMNVs can accumulate and remain in the tumor after local administration without crossing over into healthy tissue, effectively suppressing tumor invasion and proliferation and significantly prolonging the median survival time when combined with the AMF stimulation. This powerful synergistic approach has proven to be a robust and versatile nanoplatform for an effective GBM treatment.
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•Exploring the cell uptake of the free labelled nanocarrier Laponite by confocal Raman imaging.•Tracking the nanomaterial from the cell surface to the inner cell, without dye-labeling ...steps.•Raman spectroscopy is sensitive to detect Laponite signalling when it is dispersed in serum and in cell cultures.•Mapping the intracellular structures allows to discard Laponite adhesion to the membrane surface of the cell.
Laponite is a nanoplatform that has been successfully used as a new biomaterial for drug delivery, tissue engineering and bioimaging at the nanoscale. In general, a deep knowledge of the mechanism interaction of the nanomaterial with biological components in a physiological environment is highly desirable for properly characterizing its therapeutic efficacy and toxicology. Up to know, the use of fluorescent dyes labelling both, the nanomaterial and cell components, has been a requirement to characterize the cell uptake and to visualize the entrance of the nanomaterial into the cytosol and the cell nucleus. The used of fluorophores usually perturb the physiological medium and can interfere in the nanomaterial cell interaction. A new Raman imaging methodology to track the uptake and internalization of Laponite nanoparticles into J774 macrophages line cells is presented in this work. The combination of Raman spectroscopy and confocal microscopy provides direct information about the localization of the nanoparticle into the cell, through its unique vibrational fingerprint without labelling or adding dyes, and taking advantage of the fact that Laponite and biological molecules bands can be clearly differentiated.
Glioblastoma is the most common and lethal brain tumor in adults. The incorporation of temozolomide (TMZ) into the standard treatment has increased the overall survival rate of glioblastoma patients. ...Since then, significant advances have been made in understanding the benefits and limitations of TMZ. Among the latter, the unspecific toxicity of TMZ, poor solubility, and hydrolyzation are intrinsic characteristics, whereas the presence of the blood-brain barrier and some tumor properties, such as molecular and cellular heterogeneity and therapy resistance, have limited the therapeutic effects of TMZ in treating glioblastoma. Several reports have revealed that different strategies for TMZ encapsulation in nanocarriers overcome those limitations and have shown that they increase TMZ stability, half-life, biodistribution, and efficacy, offering the promise for future nanomedicine therapies in handling glioblastoma. In this review, we analyze the different nanomaterials used for the encapsulation of TMZ to improve its stability, blood half-life and efficacy, paying special attention to polymer- and lipid-based nanosystems. To improve TMZ drug resistance, present in up to 50% of patients, we detail TMZ combined therapeutic with i) other chemotherapies, ii) inhibitors, iii) nucleic acids, iv) photosensitizers and other nanomaterials for photodynamic therapy, photothermal therapy, and magnetic hyperthermia, v) immunotherapy, and vi) other less explored molecules. Moreover, we describe targeting strategies, such as passive targeting, active targeting to BBB endothelial cells, glioma cells, and glioma cancer stem cells, and local delivery, where TMZ has demonstrated an improved outcome. To finish our study, we include possible future research directions that could help decrease the time needed to move from bench to bedside.
The implementation of nanotechnology in medicine has opened new research horizons particularly in the field of therapeutic delivery. Mesoporous silica particles have emerged as biocompatible drug ...delivery systems with an enormous potential in the treatment of cancer among many other pathologies. In this review, we focus on the unique properties of these particles as chemotherapy delivery carriers. Here, we summarize the general characteristics of these nanomaterials - including their physicochemical properties and customizable surfaces - different stimuli that can be used to trigger targeted drug release, biocompatibility and finally, the drawbacks of these types of nanomaterials, highlighting some of the most important features of mesoporous silica nanoparticles in drug delivery.
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•Raman spectroscopy, in particular in the range 1000–1300 cm−1, was used to distinguish healthy astrocytes from glioma patient-derived cells.•Peaks related to DNA/RNA and cytochrome c ...have been found increased in glioma cells.•PCA-LDA analysis discriminated cancer cells from healthy astrocytes with an average accuracy of 92.5%.
Glioblastoma multiforme (GBM) is one of the most common and aggressive brain tumors. It presents a very bad prognosis with a patients’ overall survival of 12–15 months; treatment failure is mainly ascribable to tumor recurrence. The development of new tools, that could help the precise detection of the tumor border, is thus an urgent need. During the last decades, different vibrational spectroscopy techniques have been developed to distinguish cancer tissue from heathy tissue; in the present work, we compared GBM cells deriving from four patients with healthy human astrocytes using Raman spectroscopy. We have shown that the region between 1000 and 1300 cm−1 is enough informative for this discrimination, indeed highlighting that peaks related to DNA/RNA and cytochrome c are increased in cancer cells. Finally, our model has been able to discriminate cancer cells from healthy cells with an average accuracy of 92.5%. We believe that this study might help to further understand which are the essential Raman peaks exploitable in the detection of cancer cells, with important perspectives under a diagnostic point of view.
The application of nanomaterials in the fields of medicine and biotechnology is of enormous interest, particularly in the areas where traditional solutions have failed. Unfortunately, there is very ...little information on how to optimize the preparation of nanomaterials for their use in cell culture and on the effects that these can trigger on standard cellular systems. These data are pivotal in nanobiotechnology for the development of different applications and to evaluate/compare the cytotoxicity among the different nanomaterials or studies. The lack of information drives many laboratories to waste resources performing redundant comparative tests that often lead to partial answers due to differences in (i) the nature of the start-up material, (ii) the preparation, (iii) functionalization, (iv) resuspension, (v) the stability/dose of the nanomaterial, etc. These variations in addition to the different analytical systems contribute to the artefactual interpretation of the effects of nanomaterials and to inconsistent conclusions between different laboratories. Here, we present a brief review of a wide range of nanomaterials (nanotubes, various nanoparticles, graphene oxide, and liposomes) with HeLa cells as a reference cellular system. These human cells, widely used as cellular models for many studies, represent a reference system for comparative studies between different nanomaterials or conditions and, in the last term, between different laboratories.
Glioblastoma multiforme (GBM) is the most common and malignant neoplasia having origin in the brain. The current treatments involve surgery, radiotherapy, and chemotherapy, being complete surgical ...resection the best option for the patient survival chances. However, in those cases where a complete removal is not possible, radiation and chemotherapy are applied. Herein, the main challenges of chemotherapy, and how they can be overcome with the help of nanomedicine, are approached. Natural pathways to cross the blood–brain barrier (BBB) are detailed, and different in vivo studies where these pathways are mimicked functionalizing the nanomaterial surface are shown. Later, lipid‐based nanocarriers, such as liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, are presented. To finish, recent studies that have used lipid‐based nanosystems carrying not only therapeutic agents, yet also magnetic nanoparticles, are described. Although the advantages of using these types of nanosystems are explained, including their biocompatibility, the possibility of modifying their surface to enhance the cell targeting, and their intrinsic ability of BBB crossing, it is important to mention that research in this field is still at its early stage, and extensive preclinical and clinical investigations are mandatory in the close future.
Glioblastoma multiforme is one of the most common and malignant neoplasia that originates in the brain. Current therapeutic treatments own challenges that are overcome with the help of nanomedicine: for instance, lipid‐based nanocarriers are exploited to cross the blood–brain barrier and reach glioma cells, improving the therapeutic effects of chemotherapy drugs and decreasing their side effects.
There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, ...biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.
Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, the acquired drug resistance, and the ...presence of the blood-brain barrier (BBB) limit the efficacy of the current therapies, with effectiveness demonstrated only in a small subset of patients. To overcome these issues, here we propose an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. This anticancer nanoplatform consists of nutlin-3a-loaded ApoE-functionalized P(VDF-TrFE) nanoparticles, that can be remotely activated with ultrasound-based mechanical stimulations to induce drug release and to locally deliver anticancer electric cues. The combination of chemotherapy treatment with chronic piezoelectric stimulation resulted in activation of cell apoptosis and anti-proliferation pathways, induction of cell necrosis, inhibition of cancer migration, and reduction of cell invasiveness in drug-resistant GBM cells. Obtained results pave the way for the use of innovative multifunctional nanomaterials in less invasive and more focused anticancer treatments, able to reduce drug resistance in GBM.
Piezoelectric hybrid lipid-polymeric nanoparticles, efficiently encapsulating a non-genotoxic drug (nutlin-3a) and functionalized with a peptide (ApoE) that enhances their passage through the BBB, are proposed. Upon ultrasound stimulation, nanovectors resulted able to reduce cell migration, actin polymerization, and invasion ability of glioma cells, while fostering apoptotic and necrotic events. This wireless activation of anticancer action paves the way to a less invasive, more focused and efficient therapeutic strategy.
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