The investigation of the parameters affecting the ZnO nanoparticle cytotoxicity behaviour: A tutorial review

In the last 30 years the research about zinc oxide nanoparticles (ZnO NPs) and their related toxicity has shown a boom. ZnO NPs show cytotoxicity for both prokaryotic and eukaryotic cells and many studies demonstrated their selective toxicity towards cancer cells. However, with the increasing number of publications, it is observed an increase in the discrepancies obtained between the various results. Soon the scientific community understood that the ZnO NC toxicity behaviour is affected by many factors, related not only to the ZnO NPs themselves, but also to the experimental conditions used. Many recent reviews discussed these parameters by reporting experimental evidence and tried to assess the general statements about the ZnO NP cytotoxicity. This information is extremely useful for the evaluation of which type of ZnO NPs is more or less suitable for a specific study or application. However, despite that, a deep comprehension of the ZnO NP behaviour in relation to the different experimental conditions is still lacking. Actually, a full understanding of the reasons behind the NP behaviour is essential to better assess their biological activity and in particular their therapeutic application, avoiding undesired effects both in the experimental and clinical contexts. This tutorial review aims to be an experimental and practical guide for scientists that faced with the use of ZnO NPs for biomedical applications and, in particular, for their therapeutic purposes. The driving idea is to not simply summarize the results reported in the literature, but to provide instruments for a deep comprehension of the mechanisms affecting the ZnO NP cytotoxicity and behavior. This review also aims to point out the critical experimental parameters to be considered when working with these NPs, as well as the main related risks and limitations that scientists have to face

Biomimicking Extracellular Vesicles with Fully Artificial Ones: A Rational Design of EV-BIOMIMETICS toward Effective Theranostic Tools in Nanomedicine

Extracellular Vesicles (EVs) are the protagonists in cell communication and membrane trafficking, being responsible for the delivery of innumerable biomolecules and signaling moieties. At the moment, they are of paramount interest to researchers, as they naturally show incredibly high efficiency and specificity in delivering their cargo. For these reasons, EVs are employed or inspire the development of nanosized therapeutic delivery systems. In this Perspective, we propose an innovative strategy for the rational design of EV-mimicking vesicles (EV-biomimetics) for theranostic scopes. We first report on the current state-of-the-art use of EVs and their byproducts, such as surface-engineered EVs and EV-hybrids, having an artificial cargo (drug molecule, genetic content, nanoparticles, or dye incorporated in their lumen). Thereafter, we report on the new emerging field of EV-mimicking vesicles for theranostic scopes. We introduce an approach to prepare new, fully artificial EV-biomimetics, with particular attention to maintaining the natural reference lipidic composition. We overview those studies investigating natural EV membranes and the possible strategies to identify key proteins involved in site-selective natural homing, typical of EVs, and their cargo transfer to recipient cells. We propose the use also of molecular simulations, in particular of machine learning models, to approach the problem of lipid organization and self-assembly in natural EVs. We also discuss the beneficial feedback that could emerge combining the experimental tests with atomistic and molecular simulations when designing an EV-biomimetics lipid bilayer. The expectations from both research and industrial fields on fully artificial EV-biomimetics, having the same key functions of natural ones plus new diagnostic or therapeutic functions, could be enormous, as they can greatly expand the nanomedicine applications and guarantee on-demand and scalable production, off-the-shelf storage, high reproducibility of morphological and functional properties, and compliance with regulatory standards

Remotely Activated Nanoparticles for Anticancer Therapy

The present review highlights the importance of remotely activated nanoparticles for anticancer purposes.For each physical input, we present its possible active synergy with several nanomaterials.We report examples and the mechanism of action when clarified.Clinical trials involving remotely triggered nanoparticles are discussed. Cancer has nowadays become one of the leading causes of death worldwide. Conventional anticancer approaches are associated with different limitations. Therefore, innovative methodologies are being investigated, and several researchers propose the use of remotely activated nanoparticles to trigger cancer cell death. The idea is to conjugate two different components, i.e., an external physical input and nanoparticles. Both are given in a harmless dose that once combined together act synergistically to therapeutically treat the cell or tissue of interest, thus also limiting the negative outcomes for the surrounding tissues. Tuning both the properties of the nanomaterial and the involved triggering stimulus, it is possible furthermore to achieve not only a therapeutic effect, but also a powerful platform for imaging at the same time, obtaining a nano-theranostic application. In the present review, we highlight the role of nanoparticles as therapeutic or theranostic tools, thus excluding the cases where a molecular drug is activated. We thus present many examples where the highly cytotoxic power only derives from the active interaction between different physical inputs and nanoparticles. We perform a special focus on mechanical waves responding nanoparticles, in which remotely activated nanoparticles directly become therapeutic agents without the need of the administration of chemotherapeutics or sonosensitizing drugs. [Figure not available: see fulltext.

Mesoporous materials for drug delivery and theranostics

Mesoporous materials, especially those made of silica or silicon, are capturing great interest in the field of nanomedicine [...]

Correction to: Remotely Activated Nanoparticles for Anticancer Therapy (Nano-Micro Letters, (2021), 13 (11), 10.1007/s40820-020-00537-8)

In the original publication figures 7 and 11 need to be updated with correct values. The correct version of figures 7 and 11 is provided in this correction. The original article has been corrected

Editorial for special issue: Zno nanostructures for tissue regeneration, drug-delivery and theranostics applications

In recent years, zinc oxide (ZnO)-based nanomaterials have attracted a great deal of interest thanks to their outstanding and multifunctional properties [...]

Evs and bioengineering: From cellular products to engineered nanomachines

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics. The first part of this review gives an overview of the EVs naturally produced by cells and their extraction methods, focusing on the possibility to use them to carry desired cargo. The main issues for the production of the EV-based carriers are addressed, and several examples of the techniques used to upload the cargo are provided. The second part focuses on the engineered EVs, obtained through surface modification, both using direct and indirect methods, i.e., engineering of the parental cells. Several examples of the current literature are proposed to show the broad variety of engineered EVs produced thus far. In particular, we also report the possibility to engineer the parental cells to produce cargo-loaded EVs or EVs displaying specific surface markers. The third and last part focuses on the most recent advancements based on synthetic and chimeric EVs and the methods for their production. Both top-down or bottom-up techniques are analyzed, with many examples of applications

Lipidic Formulations Inspired by COVID Vaccines as Smart Coatings to Enhance Nanoparticle-Based Cancer Therapy

Recent advances in nanomedicine have led to the introduction and subsequent establishment of nanoparticles in cancer treatment and diagnosis. Nonetheless, their application is still hindered by a series of challenges related to their biocompatibility and biodistribution. In this paper, we take inspiration from the recently produced and widely spread COVID vaccines, based on the combinational use of ionizable solid lipid nanoparticles, cholesterol, PEGylated lipids, and neutral lipids able to incorporate mRNA fragments. Here, we focus on the implementation of a lipidic formulation meant to be used as a smart coating of solid-state nanoparticles. The composition of this formulation is finely tuned to ensure efficient and stable shielding of the cargo. The resulting shell is a highly customized tool that enables the possibility of further functionalizations with targeting agents, peptides, antibodies, and fluorescent moieties for future in vitro and in vivo tests and validations. Finally, as a proof of concept, zinc oxide nanoparticles doped with iron and successively coated with this lipidic formulation are tested in a pancreatic cancer cell line, BxPC-3. The results show an astonishing increase in cell viability with respect to the same uncoated nanoparticles. The preliminary results presented here pave the way towards many different therapeutic approaches based on the massive presence of highly biostable and well-tolerated nanoparticles in tumor tissues, such as sonodynamic therapy, photodynamic therapy, hyperthermia, and diagnosis by means of magnetic resonance imaging

Doped zinc oxide nanoparticles: Synthesis, characterization and potential use in nanomedicine

Smart nanoparticles for medical applications have gathered considerable attention due to an improved biocompatibility and multifunctional properties useful in several applications, including advanced drug delivery systems, nanotheranostics and in vivo imaging. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) were deeply investigated due to their peculiar physical and chemical properties. The large surface to volume ratio, coupled with a reduced size, antimicrobial activity, photocatalytic and semiconducting properties, allowed the use of ZnO NPs as anticancer drugs in new generation physical therapies, nanoantibiotics and osteoinductive agents for bone tissue regeneration. However, ZnO NPs also show a limited stability in biological environments and unpredictable cytotoxic effects thereof. To overcome the abovementioned limitations and further extend the use of ZnO NPs in nanomedicine, doping seems to represent a promising solution. This review covers the main achievements in the use of doped ZnO NPs for nanomedicine applications. Sol-gel, as well as hydrothermal and combustion methods are largely employed to prepare ZnO NPs doped with rare earth and transition metal elements. For both dopant typologies, biomedical applications were demonstrated, such as enhanced antimicrobial activities and contrast imaging properties, along with an improved biocompatibility and stability of the colloidal ZnO NPs in biological media. The obtained results confirm that the doping of ZnO NPs represents a valuable tool to improve the corresponding biomedical properties with respect to the undoped counterpart, and also suggest that a new application of ZnO NPs in nanomedicine can be envisioned

Extracellular vesicles and their current role in cancer immunotherapy

Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer