Biomimetic cell-derived nanocarriers in cancer research

Nanoparticles have now long demonstrated capabilities that make them attractive to use in biology and medicine. Some of them, such as lipid nanoparticles (SARS-CoV-2 vaccines) or metallic nanoparticles (contrast agents) are already approved for their use in the clinic. However, considering the constantly growing body of different formulations and the huge research around nanomaterials the number of candidates reaching clinical trials or being commercialized is minimal. The reasons behind being related to the “synthetic” and “foreign” character of their surface. Typically, nanomaterials aiming to develop a function or deliver a cargo locally, fail by showing strong off-target accumulation and generation of adverse responses, which is connected to their strong recognition by immune phagocytes primarily. Therefore, rendering in negligible numbers of nanoparticles developing their intended function. While a wide range of coatings has been applied to avoid certain interactions with the surrounding milieu, the issues remained. Taking advantage of the natural cell membranes, in an approach that resembles a cell transfer, the use of cell-derived surfaces has risen as an alternative to artificial coatings or encapsulation methods. Biomimetic technologies are based on the use of isolated natural components to provide autologous properties to the nanoparticle or cargo being encapsulated, thus, improving their therapeutic behavior. The main goal is to replicate the (bio)-physical properties and functionalities of the source cell and tissue, not only providing a stealthy character to the core but also taking advantage of homotypic properties, that could prove relevant for targeted strategies. Such biomimetic formulations have the potential to overcome the main issues of approaches to provide specific features and identities synthetically. In this review, we provide insight into the challenges of nano-biointerfaces for drug delivery; and the main applications of biomimetic materials derived from specific cell types, focusing on the unique strengths of the fabrication of novel nanotherapeutics in cancer therapyThe authors thank the financial support of the European Research Council (starting grant #950421), the European Union (INTERREG V-A Spain–Portugal #0624_2IQBIONEURO_6_E, NextGenerationEU/PRTR and ERDF), the MCIN/AEI (PID2020-119206RB-I00, PID2020-119479RA-I00, PID2019-111218RB-I00, RYC-2017-23457 and RYC-2019-028238-I), and the Xunta de Galicia (ED431F 2021/02, 2021-CP090, ED431C 2022/018, and Centro Singular De Investigación de Galicia Accreditation 2019–2022 #ED431G 2019/03)S

Antireflection self-reference method based on ultrathin metallic nanofilms for improving terahertz reflection spectroscopy

We present the potential of an antireflection self-reference method based on ultrathin tantalum nitride (TaN) nanofilms for improving terahertz (THz) reflection spectroscopy. The antireflection self-reference method is proposed to eliminate mutual interference caused by unwanted reflections, which significantly interferes with the important reflection from the actual sample in THz reflection measurement. The antireflection self-reference model was investigated using a wave-impedance matching approach, and the theoretical model was verified in experimental studies. We experimentally demonstrated this antireflection selfreference method can completely eliminate the effect of mutual interference, accurately recover the actual sample’s reflection and improve THz reflection spectroscopy. Our method paves the way to implement a straightforward, accurate and efficient approach to investigate THz properties of the liquids and biological samplesThe Fund from Hefei University of Technology (407-0371000019); Sichuan Province Science and Technology Support Program (No. 2016GZ0250); the Fundamental Research Funds for the Central Universities (Grant No. JD2017JGPY0006); National Natural Science Foundation of China (Grant No.51607050); MINECO (MAT2015–74381-JIN to B.P., RYC2014–16962 and CTQ2017-89588-R to P.dP.); Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016–2019, ED431G/09); European Union (European Regional Development Fund – ERDF)S

Enhanced Terahertz Radiation Generation of Photoconductive Antennas Based on Manganese Ferrite Nanoparticles

This paper presents a significant effect of manganese ferrite nanoparticles (MnFe2O4 NPs) on the increase of the surface photoconductivity of semiconductors. Herein, the optical characterization of photo-excited carriers of silicon coated with MnFe2O4 NPs was studied by using THz time-domain spectroscopy (THz-TDs). We observed that silicon coated with MnFe2O4 NPs provided a significantly enhanced attenuation of THz radiation in comparison with bare silicon substrates under laser irradiation. The experimental results were assessed in the context of a surface band structure model of semiconductors. In addition, photoconductive antennas coated with MnFe2O4 NPs significantly improved the efficiency of THz radiation generation and signal to noise ratio of the THz signal. This work demonstrates that coating with MnFe2O4 NPs could improve the overall performance of THz systems, and MnFe2O4 NPs could be further used for the implementation of novel optical devicesQ.Z. acknowledges a fellowship from the Chinese Scholarship Council. Part of the project was funded by the European Commission (grant Future NanoNeeds to WJP). Financial support from MINECO (MAT2015–74381-JIN to B.P., RYC-2014–16962 to P.dP.), the Consellería de Cultura, Educación e Ordenación Universitaria (Centro singular de investigación de Galicia accreditation 2016–2019, ED431G/09), and the European Regional Development Fund (ERDF) is gratefully acknowledgedS

Direct protein quantification in complex sample solutions by surface-engineered nanorod probes

Detecting biomarkers from complex sample solutions is the key objective of molecular diagnostics. Being able to do so in a simple approach that does not require laborious sample preparation, sophisticated equipment and trained staff is vital for point-of-care applications. Here, we report on the specific detection of the breast cancer biomarker sHER2 directly from serum and saliva samples by a nanorod-based homogeneous biosensing approach, which is easy to operate as it only requires mixing of the samples with the nanorod probes. By careful nanorod surface engineering and homogeneous assay design, we demonstrate that the formation of a protein corona around the nanoparticles does not limit the applicability of our detection method, but on the contrary enables us to conduct in-situ reference measurements, thus further strengthening the point-of-care applicability of our method. Making use of sandwich assays on top of the nanorods, we obtain a limit of detection of 110 pM and 470 pM in 10-fold diluted spiked saliva and serum samples, respectively. In conclusion, our results open up numerous applications in direct protein biomarker quantification, specifically in point-of-care settings where resources are limited and ease-of-use is of essenceThis research was supported by the European Commission FP7 NAMDIATREAM project (EU NMP4-LA-2010–246479), and the German Research Foundation (DFG grant PA 794/25-1)S

Biosensor comprising metal nanoparticles

[ES] La presente invención se refiere a un biosensor donde la detección del analito se realiza de forma visual por el cambio de color en las zonas del soporte en que el analito esté presente producido por las nanopartículas al ser irradiadas con una fuente de luz externa[EN] The present invention discloses a biosensor for visual detection of an analyte, based on the light to heat conversion properties of metal nanoparticles: the analyte is visually detected by the colour change in the support areas (where the analyte is present), produced as a result of the heat generated by the metal nanoparticles where they are irradiated with an external light source. Use of said biosensor in a method for the detection of analytes is also claimed.Peer reviewedUniversidad de Zaragoza, Fundación Agencia Aragonesa para la Investigación y el Desarrollo, Consejo Superior de Investigaciones Científicas (España)B1 Patente sin examen previ

Nanosized metal–organic frameworks as unique platforms for bioapplications

Metal–organic frameworks (MOFs) are extremely versatile materials, which serve to create platforms with exceptional porosity and specific reactivities. The production of MOFs at the nanoscale (NMOFs) offers the possibility of creating innovative materials for bioapplications as long as they maintain the properties of their larger counterparts. Due to their inherent chemical versatility, synthetic methods to produce them at the nanoscale can be combined with inorganic nanoparticles (NPs) to create nanocomposites (NCs) with one-of-a-kind features. These systems can be remotely controlled and can catalyze abiotic reactions in living cells, which have the potential to stimulate further research on these nanocomposites as tools for advanced therapiesS

New Approaches in Nanomedicine for Ischemic Stroke

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient’s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapiesThis project was supported by the FRQS, ISCIII (AC19/00031 and AC20/00041), and ANR under the framework of EuroNanoMed III_2020 (PLATMED_project); the European Union program FEDER and the European Regional Development Fund–ERDF; and the Xunta de Galicia (IN607D2020/03 and ED431G2019/03). E.P. and B.P acknowledge the AEI grants (PID2019-111218RB-I00 and RyC-2017-23457). Finally, F.C. thanks the ISCIII and Miguel Servet program (CPII19/00020)S

Nanoparticle-based immunotherapeutics: from the properties of nanocores to the differential effects of administration routes

The engagement with the immune system is one of the main cornerstones in the development of nanotechnologies for therapy and diagnostics. Recent advances have made possible the tuning of features like size, shape and biomolecular modifications that influence such interactions, however, the capabilities for immune modulation of nanoparticles are still not well defined and exploited. This review focuses on recent advances made in preclinical research for the application of nanoparticles to modulate immune responses, and the main features making them relevant for such applications. We review and discuss newest evidence in the field, which include in vivo experiments with an extensive physicochemical characterization as well as detailed study of the induced immune response. We emphasize the need of incorporating knowledge about immune response development and regulation in the design and application of nanoparticles, including the effect by parameters such as the administration route and the differential interactions with immune subsetsThe authors thank the financial support of the European Research Council (starting grant #950421), the European Union (INTERREG V-A Spain–Portugal #0624_2IQBIONEURO_6_E, NextGeneration EU/PRTR and ERDF; H2020-FET-Open grant agreement No. 899612), the MCIN/AEI (PID2020-119206RB-I00, PID2020-119479RA-I00, PID2019-111218RB-I00, RYC-2017-23457, RYC-2019-028238-I and RYC2021‐034576‐I), and the Xunta de Galicia (ED431F 2021/02, 2021-CP090, ED431C 2022/018, and Centro Singular De Investigación de Galicia Accreditation 2019–2022 #ED431G 2019/03). This project was also supported by the ISCIII, under the framework of EuroNanoMed III_2020 (AC20/00041, PLATMED)S

Plasmonic-assisted thermocyclizations in living cells using metal−organic framework based nanoreactors

We describe a microporous plasmonic nanoreactor to carry out designed near-infrared (NIR)-driven photothermal cyclizations inside living cells. As a proof of concept, we chose an intramolecular cyclization that is based on the nucleophilic attack of a pyridine onto an electrophilic carbon, a process that requires high activation energies and is typically achieved in bulk solution by heating at ∼90 °C. The core–shell nanoreactor (NR) has been designed to include a gold nanostar core, which is embedded within a metal–organic framework (MOF) based on a polymer-stabilized zeolitic imidazole framework-8 (ZIF-8). Once accumulated inside living cells, the MOF-based cloak of NRs allows an efficient diffusion of reactants into the plasmonic chamber, where they undergo the transformation upon near-IR illumination. The photothermal-driven reaction enables the intracellular generation of cyclic fluorescent products that can be tracked using fluorescence microscopy. The strategy may find different type of applications, such as for the spatio-temporal activation of prodrugsThe authors thank the financial support of the MCIN/AEI (PID2020-119206RB-I00, PID2019-108624RB-I00, CTQ2017-84767-P, RYC-2017-23457, RYC-2019-028238-I, RTI2018-093813-J-I00), the Xunta de Galicia (ED431F 2017/02, 2021-CP054, ED431C-2021/25, Centro Singular de Investigación de Galicia Accreditation 2019−2022, and ED431G 2019/03), the European Union (European Regional Development Fund − ERDF; H2020-MSCA-IF grant agreement no. 749667; H2020-MSCA-ITN grant agreement no. 860942; H2020-FET-Open grant agreement No. 899612; and INTERREG V-A Spain−Portugal, project 0624_2IQBIONEURO_6_E), and the European Research Council (starting grant no. 950421, advanced grant no. 340055). The support of the orfeo-cinqa network (CTQ2016-81797-REDC) is also kindly acknowledgedS

Core-Shell Palladium/MOF Platforms as Diffusion-Controlled Nanoreactors in Living Cells and Tissue Models

Translating the potential of transition metal catalysis to biological and living environments promises to have a profound impact in chemical biology and biomedicine. A major challenge in the field is the creation of metal-based catalysts that remain active over time. Here, we demonstrate that embedding a reactive metallic core within a microporous metal-organic framework-based cloak preserves the catalytic site from passivation and deactivation, while allowing a suitable diffusion of the reactants. Specifically, we report the fabrication of nanoreactors composed of a palladium nanocube core and a nanometric imidazolate framework, which behave as robust, long-lasting nanoreactors capable of removing propargylic groups from phenol-derived pro-fluorophores in biological milieu and inside living cells. These heterogeneous catalysts can be reused within the same cells, promoting the chemical transformation of recurrent batches of reactants. We also report the assembly of tissue-like 3D spheroids containing the nanoreactors and demonstrate that they can perform the reactions in a repeated mannerThe authors thank the financial support of the MINECO ( CTQ2017-89588-R , SAF2016-76689-R , CTQ2017-84767-P , RYC-2014-16962 , and RYC-2017-23457 ), the Xunta de Galicia ( ED431F 2017/02 , 2015-CP082 , ED431C 2017/19 , and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03 ), the European Union (European Regional Development Fund [ERDF]; H2020-MSCA-IF-2016 grant agreement no. 749667 ; and INTERREG V-A Spain-Portugal [POCTEP] 2014-2020, project 0624_2IQBIONEURO_6_E ), and the European Research Council (advanced grant no. 340055 ). Support of the orfeo-cinqa network ( CTQ2016-81797-REDC ) is also kindly acknowledgedS