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

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

Tailoring the synthesis and the functionalization of nanoparticles for nanomedicine

En este trabajo se presenta el desarrollo de nanopartículas para su utilización en bioaplicaciones. Este desarrollo comprende desde la síntesis de los nanocompuestos; pasando por su funcionalización y estabilización para su uso en medios biológicos; su caracterización fisico-química; evaluaciones previas de citotoxicidad, y terminando en el uso de estas partículas en aplicaciones específicas. En este trabajo se distinguen dos grandes bloques, en el primero se desarrolla el trabajo realizado con partículas híbridas de óxido de hierro y oro; y en el segundo y más importante en cuanto a extensión y resultados se presenta el trabajo concerniente al nanoprismas triangulares de oro. Las estructuras híbridas fueron estabilizadas en fase acuosa mediante el uso de cadenas anfifílicas sintetizadas con este propósito. Estas partículas estables en medio acuoso, presentan el doble comportamiento del oro, mostrando plasmón usperficial así como comportamiento superparamagnético debido a la presencia del óxido de hierro. Las partículas finales no presentan citotoxicidad, y fueron modificadas con un péptido de internalización para traspasar de manera exitosa la membrana celular. Además se evaluó su potencial como agentes de contraste para MRI encontrando que sus valores de relajatividad son comparables a los comerciales. El uso de estas partículas como agentes de hipertermia magnética quedó descartado debido al bajo rendimiento que mostraron. En el segundo bloque se recoge el desarrollo una nueva síntesis de nanoprismas triangulares de oro para su uso como agentes de hipertermia óptica. Ésta síntesis evita el uso de surfactantes citotóxivos como el CTAB, y produce un buen rendimiento de estructuras planas. Además, es posible el control del tamaño, y por tanto de la banda de absorción de NIR, variando la relación molar de los reactivos. Estas partículas fueron estabilizadas de manera exitosa, y se evaluó su comportamiento como agentes transductores de luz a calor mediante su irradiación con un láser infrarrojo. Esta evaluación como agentes generadores de calor se realizó tanto en solución, donde se encontró que incluso a bajas concentraciones la cantidad de energía liberada como calor es muy importante, como a nivel celular. En cuanto a su comportamiento en solución, los resultados son comparables a los mejores resultados publicados hasta el momento. Además, mediante el uso de una molécula termosensible se intentó evaluar la temperatura real en la superficie de las partículas. Por último, su uso a nivel celular, tras demostrar que las partículas no presentaban comportamiento citotóxico, demostró que este tipo de sistemas pueden ser utilizados tanto para fotoablación como para liberación de fármacos mediada por irradiación con luz. Un último experimento muestra además el potencial uso de estas partículas como agentes para imagen in vivo en fotoacústica

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