Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve ...cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing
systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research.
Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in ...early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided.
Glioblastoma multiforme is the most aggressive brain tumor, due to its high invasiveness and genetic heterogeneity. Moreover, the blood–brain barrier prevents many drugs from reaching a therapeutic ...concentration at the tumor site, and most of the chemotherapeutics lack in specificity toward cancer cells, accumulating in both healthy and diseased tissues, with severe side effects. Here, we present in vitro investigations on lipid-based nanovectors encapsulating a drug, nutlin-3a, and superparamagnetic iron oxide nanoparticles, to combine the proapoptotic action of the drug and the hyperthermia mediated by superparamagnetic iron oxide nanoparticles stimulated with an alternating magnetic field. The nanovectors are functionalized with the peptide angiopep-2 to induce receptor-mediated transcytosis through the blood–brain barrier and to target a receptor overexpressed by glioma cells. The glioblastoma multiforme targeting efficiency and the blood–brain barrier crossing abilities were tested through in vitro fluidic models, where different human cell lines were placed to mimic the tumor microenvironment. These nanovectors successfully cross the blood–brain barrier model, maintaining their targeting abilities for glioblastoma multiforme with minimal interaction with healthy cells. Moreover, we showed that nanovector-assisted hyperthermia induces a lysosomal membrane permeabilization that not only initiates a caspase-dependent apoptotic pathway, but also enhances the anticancer efficacy of the drug.
Glioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, characterized by rapid progression, resistance to treatments, and low survival rates; the development of a targeted ...treatment for this disease is still today an unattained objective. Among the different strategies developed in the latest few years for the targeted delivery of nanotherapeutics, homotypic membrane-membrane recognition is one of the most promising and efficient. In this work, we present an innovative drug-loaded nanocarrier with improved targeting properties based on the homotypic recognition of GBM cells. The developed nanoplatform consists of boron nitride nanotubes (BNNTs) loaded with doxorubicin (Dox) and coated with cell membranes (CM) extracted from GBM cells (Dox-CM-BNNTs). We demonstrated as Dox-CM-BNNTs are able to specifically target and kill GBM cells in vitro, leaving unaffected healthy brain cells, upon successful crossing an in vitro blood-brain barrier model. The excellent targeting performances of the nanoplatform can be ascribed to the protein component of the membrane coating, and proteomic analysis of differently expressed membrane proteins present on the CM of GBM cells and of healthy astrocytes allowed the identification of potential candidates involved in the process of homotypic cancer cell recognition.
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•First example of a biomimetic camouflage of boron nitride nanotubes•Evidence of homotypic targeting of boron nitride nanotubes•Extensive proteomics investigations describing the homotypic targeting•Systematic investigations on in vitro complex systems, including multi-cellular fluidic models and blood-brain barrier models
Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among ...others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in the scientific and medical fields. Indeed, they can act as cancer‐preventing agents, antimutagens, apoptosis inducers, efficient antioxidants, as well as antimicrobial and immunomodulatory molecules. Moreover, thanks to their peculiar optical properties, they can be exploited as photosensitizers for photodynamic therapy and as vision enhancers. Most of these molecules, however, are highly hydrophobic and poorly soluble in biological fluids, and may display undesired toxicity due to accumulation in healthy tissues. The advent of nanomedicine has prompted the development of nanoparticles acting as carriers for chlorophyll derivatives, facilitating their targeted administration with demonstrated applicability in diagnosis and therapy. In this review, the chemical and physical properties of chlorophyll derivatives that justify their usage in the biomedical field, with particular regard to light‐activated dynamics are described. Their role as antioxidants and photoactive agents are discussed, introducing the most recent nanomedical applications and focusing on inorganic and organic nanocarriers exploited in vitro and in vivo.
Chlorophyll derivatives can be easily obtained from natural sources and have unique optical properties that raises a huge interest in the scientific community. In particular, they can be used in light‐activated biomedical applications such as photodynamic therapy, vision enhancement and recovery, or optogenetics. Nanotechnology has significantly improved their bioavailability, stability, and their targeted administration.
The modeling of the pathological microenvironment of the central nervous system (CNS) represents a disrupting approach for drug screening for advanced therapies against tumors and neuronal disorders. ...The in vitro investigations of the crossing and diffusion of drugs through the blood–brain barrier (BBB) are still not completely reliable, due to technological limits in the replication of 3D microstructures that can faithfully mimic the in vivo scenario. Here, an innovative 1:1 scale 3D‐printed realistic biohybrid model of the brain tumor microenvironment, with both luminal and parenchyma compartments, is presented. The dynamically controllable microfluidic device, fabricated through two‐photon lithography, enables the triple co‐culture of hCMEC/D3 cells, forming the internal biohybrid endothelium of the capillaries, of astrocytes, and of magnetically‐driven spheroids of U87 glioblastoma cells. Tumor spheroids are obtained from culturing glioblastoma cells inside 3D microcages loaded with superparamagnetic iron oxide nanoparticles (SPIONs). The system proves to be capable in hindering dextran diffusion through the bioinspired BBB, while allowing chemotherapy‐loaded nanocarriers to cross it. The proper formation of the selective barrier and the good performance of the anti‐tumor treatment demonstrate that the proposed device can be successfully exploited as a realistic in vitro model for high‐throughput drug screening in CNS diseases.
This real‐scale 3D‐printed biohybrid microfluidic device can mimic the glioblastoma microenvironment at level of the blood–brain barrier. It allows the triple co‐culture of endothelial cells, astrocytes, and magnetically‐driven spheroids of U87 glioblastoma cells. The device demonstrates to be successfully exploitable as a realistic in vitro model for high‐throughput drug screening in central nervous system diseases.
Angiogenesis plays a fundamental role in tumor development, as it is crucial for tumor progression, metastasis development, and invasion. In this view, anti-angiogenic therapy has received ...considerable attention in several cancer types in order to inhibit tumor vascularization, and the progress of nanotechnology offers opportunities to target and release anti-angiogenic agents in specific diseased areas. In this work, we showed that the angiogenic behavior of human cerebral microvascular endothelial cells can be inhibited by using nutlin-3a-loaded ApoE-functionalized polymeric piezoelectric nanoparticles, which can remotely respond to ultrasound stimulation. The anti-angiogenic effect, derived from the use of chemotherapy and chronic piezoelectric stimulation, leads to disruption of tubular vessel formation, decreased cell migration and invasion, and inhibition of angiogenic growth factors in the presence of migratory cues released by the tumor cells. Overall, the proposed use of remotely activated piezoelectric nanoparticles could provide a promising approach to hinder tumor-induced angiogenesis.
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•Nutlin-3a-loaded ApoE-functionalized polymeric piezoelectric nanoparticles hinder tumor-induced angiogenesis.•Reduced vessel formation, decreased cell invasion, and inhibition of angiogenesis-related cytokines are demonstrated.•The therapeutic efficacy of the drug is enhanced after ultrasound stimulation.
Catanionic vesicles were prepared by mixing nonstoichiometric amounts of sodium bis(2-ethylhexyl) sulfosuccinate and dioctyldimethylammonium bromide in water. Depending on the concentration and mole ...ratios between the surfactants, catanionic vesicular aggregates are formed. They have either negative or positive charges in excess and are endowed with significant thermodynamic and kinetic stability. Vesicle characterization was performed by dynamic light scattering and electrophoretic mobility. It was inferred that vesicle size scales in inverse proportion with its surface charge density and diverges as the latter quantity approaches zero and/or the mole ratio equals unity. Therefore, both variables are controlled by the anionic/cationic mole ratio. Small-angle X-ray scattering, in addition, indicates that vesicles are unilamellar. Selected anionic vesicular systems were reacted with poly-l-lysine hydrobromide or lysozyme. Polymer binding continues until complete neutralization of the negatively charged sites on the vesicles surface is attained, as inferred by electrophoretic mobility. Lipoplexes are formed as a result of significant electrostatic interactions between cationic polyelectrolytes and negatively charged vesicles.
Oxidative stress occurs when physiological antioxidant systems do not manage to counteract the excessive intracellular production of reactive oxygen species (ROS), which accumulate leading to ...irreversible oxidation of DNA and other biomacromolecules, and thus to the onset of pathological conditions. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease characterized by autosomal recessive mutations in the sacsin gene (
). It has been demonstrated that cells of ARSACS patients show bioenergetic and mitochondrial impairment, denoted by reduced respiratory chain activities and ATP synthesis. In order to design a suitable therapy for ARSACS, it is essential to consider that treatments need to cross the blood-brain barrier (BBB), a specialized structure that separates the subtle environment of the brain from blood circulation. Nanostructured lipid carriers (NLCs), constituted by a solid lipid shell and a liquid lipid phase in the core, have been fabricated for loading hydrophobic molecules, improving their bioavailability. Idebenone (IDE), a synthetic analogue of coenzyme Q
, is able to inhibit lipid peroxidation and detoxify several free radicals. However, because of its poor solubility, it requires
drug-delivery systems for enhancing its pharmacokinetic properties, preventing undesired cytotoxicity. In this work, NLCs loaded with idebenone (IDE-NLCs) have been prepared. The nanovectors have been physicochemically characterized, and their biological activity has been evaluated on different central nervous system cell lines. IDE-NLCs demonstrated to be stable in water and in cell culture media, and showed a sustained drug release profile. Interestingly, preliminary data demonstrated their ability to permeate an
BBB model. Their protective antioxidant activity in human healthy primary skin fibroblasts and their therapeutic efficacy in ARSACS-derived primary skin fibroblasts have been also investigated, showing their potential for future development as therapeutic agents.
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