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

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

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

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

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

Aqueous Stable Gold Nanostar/ZIF‐8 Nanocomposites for Light‐Triggered Release of Active Cargo Inside Living Cells

This is the peer reviewed version of the following article: C. Carrillo-Carrión, R. Martínez, M. F. Navarro Poupard, B. Pelaz, E. Polo, A. Arenas-Vivo, A. Olgiati, P. Taboada, M. G. Soliman, Ú. Catalán, S. Fernández-Castillejo, R. Solà, W. J. Parak, P. Horcajada, R. A. Alvarez-Puebla, P. del Pino, Angew. Chem. Int. Ed. 2019, 58, 7078, which has been published in final form at https:// doi.org/10.1002/anie.201902817. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsA plasmonic core–shell gold nanostar/zeolitic‐imidazolate‐framework‐8 (ZIF‐8) nanocomposite was developed for the thermoplasmonic‐driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF‐8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule‐release mechanism relies on the use of near‐IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface‐enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near‐IR‐triggered cargo release inside cells, thereby leading to DNA stainingThis work has received financial support from the MINECO‐Spain (MAT2016‐80266‐R, MAT2015‐74381‐JIN, CTQ2017‐88648R, ENE2016‐79608‐C2‐1‐R, CTQ2017‐89588‐R, RYC‐2014‐15039, RYC‐2014‐16962), the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019 (ED431G/09), the Agrupación Estratégica de Materiales Action (ED431E 2018/08), the Generalitat de Cataluña (2017SGR522, 2017SGR883, SLT002/16/00239), the URV (2017PFR‐URV‐B2‐02), the German Research Society (DFG PA 794‐21‐1), and the European Union (European Regional Development Fund—ERDF, H2020‐MSCA‐IF‐2016, project 749667). M.F.N.P acknowledges the CONACYT PhD fellowship programS

Fusogenic Cell-Derived nanocarriers for cytosolic delivery of cargo inside living cells

A surface-engineered cell-derived nanocarrier was developed for efficient cytosolic delivery of encapsulated biologically active molecules inside living cells. Thus, a combination of aromatic-labeled and cationic lipids, instrumental in providing fusogenic properties, was intercalated into the biomimetic shell of self-assembled nanocarriers formed from cell membrane extracts. The nanocarriers were loaded, as a proof of concept, with either bisbenzimide molecules, a fluorescently labeled dextran polymer, the bicyclic heptapeptide phalloidin, fluorescently labeled polystyrene nanoparticles or a ribonucleoprotein complex (Cas9/sgRNA). The demonstrated nanocarrieŕs fusogenic behavior relies on the fusogen-like properties imparted by the intercalated exogenous lipids, which allows for circumventing lysosomal storage, thereby leading to efficient delivery into the cytosolic milieu where cargo regains functionThe 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). This project was also supported by the ISCIII, under the framework of EuroNanoMed III_2020 (AC20/00041, PLATMED). We would also like to thank our colleagues Dr. M. Collado and Dr. M.A. Moreno-Mateos for their valuable insights and suggestions. We thank Dr. M. Collado (IDIS, Spain) for a gift of 293-T-HEK-dEGFP cellsS