Summary: Molecular viewers’ long learning curve is hindering researchers in approaching the field of structural biology for the first time. Herein, we present ‘The Protein Imager’, a lightweight, powerful and easy-to-use interface as a next-gen online molecular viewer. Furthermore, the interface is linked to an automated server-side rendering system able to generate publication-quality molecular illustrations. The Protein Imager interface has been designed for easy usage for beginners and experts in the field alike. The interface allows the preparation of very complex molecular views maintaining a high level of responsiveness even on mobile devices. Availability and implementation: The Protein Imager interface is freely available online at https://3dproteinimaging.com/protein-imager. Supplementary information: Supplementary data are available at Bioinformatics online.

Nanomedicine has been considered a promising tool for biomedical research and clinical practice in the 21st century because of the great impact nanomaterials could have on human health. The generation of new smart nanomaterials, which enable time- and space-controlled drug delivery, improve the limitations of conventional treatments, such as non-specific targeting, poor biodistribution and permeability. These smart nanomaterials can respond to internal biological stimuli (pH, enzyme expression and redox potential) and/or external stimuli (such as temperature, ultrasound, magnetic field and light) to further the precision of therapies. To this end, photonic and magnetic nanoparticles, such as gold, silver and iron oxide, have been used to increase sensitivity and responsiveness to external stimuli. In this review, we aim to report the main and most recent systems that involve photonic or magnetic nanomaterials for external stimulus-responsive drug release. The uniqueness of this review lies in highlighting the versatility of integrating these materials within different carriers. This leads to enhanced performance in terms of in vitro and in vivo efficacy, stability and toxicity. We also point out the current regulatory challenges for the translation of these systems from the bench to the bedside, as well as the yet unresolved matter regarding the standardization of these materials.

The contactless heating capacity of magnetic nanoparticles (MNPs) has been exploited in fields such as hyperthermia cancer therapy, catalysis, and enzymatic thermal regulation. Herein, we propose an advanced technology to generate multiple local temperatures in a single-pot reactor by exploiting the unique nanoheating features of iron oxide MNPs exposed to alternating magnetic fields (AMFs). The heating power of the MNPs depends on their magnetic features but also on the intensity and frequency conditions of the AMF. Using a mixture of diluted colloids of MNPs we were able to generate a multi-hot-spot reactor in which each population of MNPs can be selectively activated by adjusting the AMF conditions. The maximum temperature reached at the surface of each MNP was registered using independent fluorescent thermometers that mimic the molecular link between enzymes and MNPs. This technology paves the path for the implementation of a selective regulation of multienzymatic reactions.

Iron oxide nanoparticles (NPs) are attractive materials for enzyme immobilization and, thanks to their superparamagnetism, can be accessed by remote stimuli. This can be exploited to activate molecules that are not remotely actuable. Here, we demonstrate that thermophilic enzymes chemically linked to NPs can be activated in a "wireless" fashion by an external alternate magnetic field (AMF). To this aim, we have conjugated, with different binding strategies, the thermophilic enzymes α-amylase and l-aspartate oxidase to iron oxide NPs obtaining NP-enzyme systems with activities depending on the different orientations and stretching of the enzymes. Since enzyme activation occurs without a significant rise of the "overall" temperature of the systems, we have speculated a local NP-enzyme heating that does not immediately interest the rest of the solution that remains at relatively low temperature, low enough to allow non-thermophilic enzymes to work together with the NP-conjugated thermophilic enzymes. Nanoactuation of thermophilic enzymes by AMF has potential applications in different fields. Indeed, multi-enzymatic processes with enzymes with different temperature optima could be carried out in the same reaction pot and thermolabile products could be efficiently produced by thermophilic enzymes without suffering for the high temperatures. Moreover, our findings represent a proof of concept of the possibility to achieve a fine-tuning of the enzyme-NP system with the aim to intervene in cell metabolism.

Herein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (T_opt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects.