Ultrafast Directional Janus Pt-Mesoporous Silica Nanomotors for Smart Drug Delivery

[EN] Development of bioinspired nanomachines with an efficient propulsion and cargo-towing has attracted much attention in the last years due to their potential biosensing, diagnostics, and therapeutics applications. In this context, self-propelled synthetic nanomotors are promising carriers for intelligent and controlled release of therapeutic payloads. However, the implementation of this technology in real biomedical applications is still facing several challenges. Herein, we report the design, synthesis, and characterization of innovative multifunctional gated platinum¿mesoporous silica nanomotors constituted of a propelling element (platinum nanodendrite face), a drug-loaded nanocontainer (mesoporous silica nanoparticle face), and a disulfide-containing oligo(ethylene glycol) chain (S¿S¿PEG) as a gating system. These Janus-type nanomotors present an ultrafast self-propelled motion due to the catalytic decomposition of low concentrations of hydrogen peroxide. Likewise, nanomotors exhibit a directional movement, which drives the engines toward biological targets, THP-1 cancer cells, as demonstrated using a microchip device that mimics penetration from capillary to postcapillary vessels. This fast and directional displacement facilitates the rapid cellular internalization and the on-demand specific release of a cytotoxic drug into the cytosol, due to the reduction of the disulfide bonds of the capping ensemble by intracellular glutathione levels. In the microchip device and in the absence of fuel, nanomotors are neither able to move directionally nor reach cancer cells and deliver their cargo, revealing that the fuel is required to get into inaccessible areas and to enhance nanoparticle internalization and drug release. Our proposed nanosystem shows many of the suitable characteristics for ideal biomedical destined nanomotors, such as rapid autonomous motion, versatility, and stimuli-responsive controlled drug release.The authors want to thank the Spanish Government for RTI2018-100910-B-C41 (MCIU/AEI/FEDER, UE) and CTQ2017-87954-P projects and the Generalitat Valenciana for support by project PROMETEO/2018/024. P.D. thanks the Spanish government for her Juan de la Cierva postdoctoral fellowship. E.L.-S. thanks MINECO for her FPU fellowship. A.E. is also grateful for her Ph.D. grant by the Generalitat Valenciana.Diez-Sánchez, P.; Lucena-Sánchez, E.; Escudero-Noguera, A.; Llopis-Lorente, A.; Villalonga, R.; Martínez-Máñez, R. (2021). Ultrafast Directional Janus Pt-Mesoporous Silica Nanomotors for Smart Drug Delivery. ACS Nano. 15(3):4467-4480. https://doi.org/10.1021/acsnano.0c084044467448015

Ficin-Cyclodextrin-Based Docking Nanoarchitectonics of Self-Propelled Nanomotors for Bacterial Biofilm Eradication

[EN] Development of bioinspired nanomotors showing effective propulsion and cargo delivery capabilities has attracted much attention in the last few years due to their potential use in biomedical applications. However, implementation of this tech-nology in realistic settings is still a barely explored field. Herein, we report the design and application of a multifunctional gated Janus platinum-mesoporous silica nanomotor constituted of a propelling element (platinum nanodendrites) and a drug-loaded nano-container (mesoporous silica nanoparticle) capped with ficin enzyme modified with beta-cyclodextrins (beta-CD). The engineered nanomotor is designed to effectively disrupt bacterial biofilms via H2O2-induced self-propelled motion, ficin hydrolysis of the extracellular polymeric matrix (EPS) of the biofilm, and controlled pH-triggered cargo (vancomycin) delivery. The effective synergic antimicrobial activity of the nanomotor is demonstrated in the elimination of Staphylococcus aureus biofilms. The nanomotor achieves 82% of EPS biomass disruption and a 96% reduction in cell viability, which contrasts with a remarkably lower reduction in biofilm elimination when the components of the nanomotors are used separately at the same concentrations. Such a large reduction in biofilm biomass in S. aureus has never been achieved previously by any conventional therapy. The strategy proposed suggests that engineered nanomotors have great potential for the elimination of biofilms.The authors acknowledge financial support from Project CIPROM/2021/007 from the Generalitat Valenciana. This research was also supported by projects PID2021-126304OB-C41 and PID2021-128141OB-C22 funded by MCIN/AEI/10.13039/501100011033/ and by the European Regional Development Fund - A way of doing Europe. This study was also part of the Advanced Materials Program (MFA/2022/053) supported by MCIN with funding from the European Union NextGenerationEU (PRTR-C17.I1) and by Generalitat Valenciana. This research was also funded by Universitat Politecnica de Valencia and the FISABIO Foundation, NANO-DRILL Project (UGP-19-384), and NANODONT Project (UPV-FISABIO-2020-B14). The authors gratefully acknowledge the support of the European Research Council (ERC) via the Advanced Grant (101052997, EDISON). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Research Council . Neither the European Union nor the granting authority can be held responsible for them. M.Z. thanks for her FPU Ph.D. scholarship by the Spanish government (FPU17/01302). A.E. is also grateful for her Ph.D. grant from the Generalitat Valenciana (ACIF/2018/110). P.D. thanks Instituto de Salud Carlos III and the European Social Fund for financial support "Sara Borrell" (CD20/00120). V.M-C. acknowledges financial support from Project CIDE-GENT/2020/031, funded by Generalitat Valenciana. Scheme 1, (top) and Figure 3a were created with BioRender.com.Ziemyte, M.; Escudero-Noguera, A.; Diez-Sánchez, P.; Ferrer, MD.; Murguía, JR.; Martí-Centelles, V.; Mira, A.... (2023). Ficin-Cyclodextrin-Based Docking Nanoarchitectonics of Self-Propelled Nanomotors for Bacterial Biofilm Eradication. Chemistry of Materials. 35(11):4412-4426. https://doi.org/10.1021/acs.chemmater.3c0058744124426351

Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy

[EN] Cancer immunotherapy has emerged in the past decade as a promising strategy for treating many forms of cancer by stimulating the patient's immune system. Although immunotherapy has achieved some promising results in clinics, more efforts are required to improve the limitations of current treatments related to lack of effective and targeted cancer antigens delivery to immune cells, dose-limiting toxicity, and immune-mediated adverse effects, among others. In recent years, the use of nanomaterials has proven promising to enhance cancer immunotherapy efficacy and reduce side effects. Among nanomaterials, attention has been recently paid to mesoporous silica nanoparticles (MSNs) as a potential multiplatform for enhancing cancer immunotherapy by considering their unique properties, such as high porosity, and good biocompatibility, facile surface modification, and self-adjuvanticity. This review explores the role of MSN and other nano/micro-materials as an emerging tool to enhance cancer immunotherapy, and it comprehensively summarizes the different immunotherapeutic strategies addressed to date by using MSN.B.E.-N., A.E., and E.L.-S. contributed equally to this work. The authors would like to thank the Spanish Government for RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (Project PROMETEO 2018/024) for support by Project PROMETEO/2018/024. A.G.-F. acknowledges her current Margarita Salas postdoctoral fellowship from UPV-MIU and "Next Generation EU" program. B.E.-N. is grateful to the Spanish Instituto de Salud Carlos III (ISCIII) for the grant through Project "IFI19/00026", co-funded by European Union. A.E. is grateful for her Ph.D. grant by the Generalitat Valenciana. E.L.-S. thanks MINECO for her FPU fellowship.Escriche-Navarro, B.; Escudero-Noguera, A.; Lucena-Sánchez, E.; Sancenón Galarza, F.; García-Fernández, A.; Martínez-Máñez, R. (2022). Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy. Advanced Science. 9(26):1-24. https://doi.org/10.1002/advs.20220075612492

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P <.001). Overall motor and cognitive performance (P <.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P <.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P <.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P <.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients