Graphene-Based Nanotechnology in Neurodegenerative Disorders

Graphene-based materials (GBMs) demonstrate unique electrochemical, mechanical, thermal, and optical properties rendering them attractive candidates for numerous biomedical applications. Since graphene's discovery, GBMs have been at the forefront of biomedical research offering innovative solutions for numerous diseases, including neurodegenerative disorders (NDs). There are numerous reviews in which synthesis and functionalization methods of GBMs are discussed. However, this review focuses specifically on the recent research advances of GBMs for NDs, and more specifically, on sensing and therapeutic applications. After a short description of NDs' main characteristics, significant attention is given to the functionalization strategies used to improve the biomedical properties of GBMs, and recent applications for Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. A description of the use of GBMs and neural stem cell technology and known toxicity issues, followed by several limitations that current GBMs need to overcome, completes this review.Peer reviewe

Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases

Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) comprise a category of versatile drug delivery systems that have been used in the biomedical field for > 25 years. SLNs and NLCs have been used for the treatment of various diseases including cardiovascular and cerebrovascular, and are considered a standard treatment for the latter, due to their inherent ability to cross the blood brain barrier (BBB). In this review, a presentation of the most important brain diseases (brain cancer, ischemic stroke, Alzheimer's disease, Parkinson's disease and multiple sclerosis) is approached, followed by the basic fabrication techniques of SLNs and NLCs. A detailed description of the reported studies of the last seven years, of active and passive targeting SLNs and NLCs for the treatment of glioblastoma multiforme and of other brain cancers, as well as for the treatment of neurodegenerative diseases is also carried out. Finally, a brief description of the advantages, the disadvantages, and the future perspectives in the use of these nanocarriers is reported, aiming at giving an insight of the limitations that have to be overcome in order to result in a delivery system with high therapeutic efficacy and without the limitations of the existing nano-systems

Progress in Stimuli-Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasing mortality rates suggest the need for more advanced strategies for their treatment. One of these strategies lies in the use of stimuli-responsive biomaterials. These "smart" biomaterials can specifically target the diseased tissue, and after "reading" the altered environmental cues, they can respond by altering their physicochemical properties and/or their morphology. In this review, the progress in the field of stimuli-responsive biomaterials for CCVDs in the last five years, aiming at highlighting their potential as early-stage therapeutics in the preclinical scenery, is described.Peer reviewe

Innovative nanotechnology tools for the functional control and tracking of human stem cells

The precise control of stem cell behavior, including differentiation, transdifferentiation, and reprog-ramming, is fundamental for safely and efficiently using human stem cells in regenerative medicine. Thanks to recent innovations and developments in the field of nanomedicine, as well as its integration with advanced molecular biology approaches, the possibility of engineering and restoring functions of complex tissues become reality. Multifunctional nanotechnological tools allow to finely control the release of growth factors, mRNA, and other molecules, to promote cell fate conversion, and to perform long-term tracking in vivo. Furthermore, stimulation approaches based on smart and biocompatible nanotransducers promise to remotely modulate the stem cell activity, paving the way for the actual exploitation of these technologies in the internal tissues of large-sized animals. In this review, the most innovative nanotechnology tools applied to stem cell-based regenerative medicine are presented, and their implications for future research and clinics are discussed.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

CeO2 Nanoparticles-Loaded pH-Responsive Microparticles with Antitumoral Properties as Therapeutic Modulators for Osteosarcoma

Osteosarcoma is an aggressive form of bone cancer mostly affecting young people. To date, the most effective strategy for the treatment of osteosarcoma is the surgical removal of the tumor with or without combinational chemotherapy. In this study, we present the development of a pH-sensitive drug-delivery system in the form of microparticles, with increased chemotherapeutic action against the osteosarcoma cell line SAOS-2, and with reduced toxicity against the heart myoblastic cell line H9C2. The delivery system is composed of calcium carbonate and collagen type I, and is loaded with cerium dioxide (CeO2) nanoparticles (<25 nm) and the anticancer drug doxorubicin. The fabricated microparticles were fully characterized morphologically and physicochemically, and their ability to induce or inhibit apoptosis/necrosis was assessed using in vitro functional assays and flow cytometry. The results presented in this study show that the highest concentration (250 μg/mL) of the therapeutic microparticles (CaCO3-based therapeutic modulators (C-TherMods)), which corresponds to 6.4 μg/mL of encapsulated doxorubicin, can protect the H9C2 cells even after 120 h, since the percentage of viable cells at this time point is 65%. On the contrary, when H9C2 cells are treated with 0.5 μg/mL of free doxorubicin, 75% of the cells are dead only after 24 h. When SAOS-2 cells are treated with the same concentration of C-TherMods (250 μg/mL), the viability of SAOS-2 cells is 80% after 24 h, while it reduces to 50% after 120 h. At pH 6.0, the synergic effect of the pro-oxidant CeO2nanoparticles and of the encapsulated doxorubicin leads to almost 100% of cell death, even at the lowest concentration of C-TherMods (50 μg/mL)

Exploiting the layer-by-layer nanoarchitectonics for the fabrication of polymer capsules: A toolbox to provide multifunctional properties to target complex pathologies

[EN] Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive techniques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thoroughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multifunctional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized.The authors are thankful for funds from the Basque Government, Department of Education (IT-927-16 and PIBA_2021_1_0048)

Nanoparticles-based phototherapy systems for cancer treatment : Current status and clinical potential

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.Peer reviewe

Polydopamine nanoparticles as an organic and biodegradable multitasking tool for neuroprotection and remote neuronal stimulation

Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as well as a photo-thermal conversion platform able to stimulate neuronal activity. L-PDNPs showed the ability to counteract reactive oxygen species (ROS) accumulation in differentiated SH-SY5Y, prevented mitochondrial ROS-induced dysfunctions, and stimulated neurite outgrowth. Moreover, for the first time in the literature, the photo-thermal conversion capacity of L-PDNPs was used to increase the intracellular temperature of neuron-like cells through near-infrared (NIR) laser stimulation, and this phenomenon was thoroughly investigated using a fluorescent temperature-sensitive dye and modeled from a mathematical point of view. It was also demonstrated that the increment in temperature caused by the NIR stimulation of L-PDNPs was able to produce a Ca2+ influx in differentiated SH-SY5Y, being, to the best of our knowledge, the first example of organic nanostructures used in such an approach. This work could pave the way to new and exciting applications of polydopamine-based and of other NIR-responsive antioxidant nanomaterials in neuronal research

Non-viral nanoparticles for RNA interference : Principles of design and practical guidelines

Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe