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Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme. Addition of glucose leads to the enzymatic production of H 2 O 2 and gluconic acid, being the first compound catalytically decomposed at the Ir nanoparticle face producing O 2 and causing the nanomachine propulsion. Gluconic acid leads to a pH reduction at the nanomachine microenvironment causing the disruption of the gating mechanism with the subsequent cargo release. This work demonstrates that enzyme-mediated self-propulsion improved release efficiency being this nanomotor successfully employed for the smart release of Doxorubicin in HeLa cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Photodynamic Therapy is a therapy based on combining a non-toxic compound, known as photosensitizer (PS), and irradiation with light of the appropriate wavelength to excite the PS molecule. The photon absorption by the PS leads to reactive oxygen species generation and a subsequent oxidative burst that causes cell damage and death. In this work, we report an antimicrobial nanodevice that uses the activity of curcumin (Cur) as a PS for antimicrobial Photodynamic Therapy (aPDT), based on mesoporous silica nanoparticles in which the action of the classical antibiotic PMB is synergistically combined with the aPDT properties of curcumin to combat bacteria. The synergistic effect of the designed gated device in combination with irradiation with blue LED light (470 nm) is evaluated against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. The results show that the nanodevice exhibits a noteworthy antibacterial activity against these microorganisms, a much more significant effect than free Cur and PMB at equivalent concentrations. Thus, 0.1 µg/mL of MSNs-Cur-PMB eliminates a bacterial concentration of about 10 5 CFU/mL of E. coli, while 1 µg/mL of MSNs-Cur-PMB is required for P. aeruginosa and S. epidermidis. In addition, antibiofilm activity against the selected bacteria was also tested. We found that 0.1 mg/mL of MSNs-Cur-PMB inhibited 99 % biofilm formation for E. coli, and 1 mg/mL of MSNs-Cur-PMB achieved 90 % and 100 % inhibition of biofilm formation for S. epidermidis and P. aeruginosa, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Engineering chemical communication between micro/nanosystems (via the exchange of chemical messengers) is receiving increasing attention from the scientific community. Although a number of micro- and nanodevices (e.g., drug carriers, sensors, and artificial cells) have been developed in the last decades, engineering communication at the micro/nanoscale is a recent emergent topic. In fact, most of the studies in this research area have been published within the last 10 years. Inspired by nature─where information is exchanged by means of molecules─the development of chemical communication strategies holds wide implications as it may provide breakthroughs in many areas including nanotechnology, artificial cell research, biomedicine, biotechnology, and ICT. Published examples rely on nanotechnology and synthetic biology for the creation of micro- and nanodevices that can communicate. Communication enables the construction of new complex systems capable of performing advanced coordinated tasks that go beyond those carried out by individual entities. In addition, the possibility to communicate between synthetic and living systems can further advance our understanding of biochemical processes and provide completely new tailored therapeutic and diagnostic strategies, ways to tune cellular behavior, and new biotechnological tools. In this Account, we summarize advances by our laboratories (and others) in the engineering of chemical communication of micro- and nanoparticles. This Account is structured to provide researchers from different fields with general strategies and common ground for the rational design of future communication networks at the micro/nanoscale. First, we cover the basis of and describe enabling technologies to engineer particles with communication capabilities. Next, we rationalize general models of chemical communication. These models vary from simple linear communication (transmission of information between two points) to more complex pathways such as interactive communication and multicomponent communication (involving several entities). Using illustrative experimental designs, we demonstrate the realization of these models which involve communication not only between engineered micro/nanoparticles but also between particles and living systems. Finally, we discuss the current state of the topic and the future challenges to be addressed.

Mesoporous silica nanoparticles (MSNs) are amongst the most used nanoparticles in biomedicine. However, the potentially toxic effects of MSNs have not yet been fully evaluated, being a controversial matter in research. In this study, bare MSNs, PEGylated MSNs (MSNs-PEG), and galacto-oligosaccharide-functionalized MSNs (MSNs-GAL) are synthesized and characterized to assess their genotoxicity and transforming ability on human lung epithelial BEAS-2B cells in short- (48 h) and long-term (8 weeks) exposure scenarios. Initial short-term treatments show a dose-dependent increase in genotoxicity for MSNs-PEG-treated cells but not oxidative DNA damage for MSNs, MSNs-PEG, or for MSNs-GAL. In addition, after 8 weeks of continuous exposure, neither induced genotoxic nor oxidative DNA is observed. Nevertheless, long-term treatment with MSNs-PEG and MSNs-GAL, but not bare MSNs, induces cell transformation features, as evidenced by the cell's enhanced ability to grow independently of anchorage, to migrate, and to invade. Further, the secretome from cells treated with MSNs and MSNs-GAL, but not MSNs-PEG, shows certain tumor-promoting abilities, increasing the number and size of HeLa cell colonies formed in the indirect soft-agar assay. These results show that MSNs, specifically the functionalized ones, provoke some measurable adverse effects linked to tumorigenesis. These effects are in the order of other nanomaterials, such as carbon nanotubes or cerium dioxide nanoparticles, but they are lower than those provoked by some approved drugs, such as doxorubicin or dexamethasone.

Mesoporous silica nanoparticles (MSNs) have attracted the attention of chemists, who have developed numerous systems for the encapsulation of a plethora of molecules, allowing the use of mesoporous silica nanoparticles for biomedical applications. MSNs have been extensively studied for their use in nanomedicine, in applications such as drug delivery, diagnosis, and bioimaging, demonstrating significant in vivo efficacy in different preclinical models. Nevertheless, for the transition of MSNs into clinical trials, it is imperative to understand the characteristics that make MSNs effective and safe. The biosafety properties of MSNs in vivo are greatly influenced by their physicochemical characteristics such as particle shape, size, surface modification, and silica framework. In this review, we compile the most relevant and recent progress in the literature up to the present by analyzing the contributions on biodistribution, biodegradability, and clearance of MSNs. Furthermore, the ongoing clinical trials and the potential challenges related to the administration of silica materials for advanced therapeutics are discussed. This approach aims to provide a solid overview of the state-of-the-art in this field and to encourage the translation of MSNs to the clinic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Glioblastoma is the most common and lethal brain cancer. New treatments are needed. However, the presence of the blood-brain barrier is limiting the development of new treatments directed toward the brain, as it restricts the access and distribution of drugs to the CNS. Materials & methods: In this work, two different nanoparticles (i.e., mesoporous silica nanoparticles and magnetic mesoporous silica nanoparticles) loaded with ponatinib were prepared. Results & conclusion: Both particles were characterized and tested in vitro and in vivo , proving that they are not toxic for blood-brain barrier cells and they increase the amount of drug reaching the brain when administered intranasally in comparison with the results obtained for the free drug.

Despite advances in breast cancer treatment, it remains the leading cause of cancer-related death in women worldwide. In this context, microRNAs have emerged as potential therapeutic targets but still present some limitations for in vivo applications. Particularly, miR-200c-3p is a well-known tumor suppressor microRNA that inhibits tumor progression and metastasis in breast cancer through downregulating ZEB1 and ZEB2 . Based on the above, we describe the design and validation of a nanodevice using mesoporous silica nanoparticles for miR-200c-3p delivery for breast cancer treatment. We demonstrate the biocompatibility of the synthesized nanodevices as well as their ability to escape from endosomes/lysosomes and inhibit tumorigenesis, invasion, migration, and proliferation of tumor cells in vitro . Moreover, tumor targeting and effective delivery of miR-200c-3p from the nanoparticles in vivo are confirmed in an orthotopic breast cancer mouse model, and the therapeutic efficacy is also evidenced by a decrease in tumor size and lung metastasis, while showing no signs of toxicity. Overall, our results provide evidence that miR-200c-3p-loaded nanoparticles are a potential strategy for breast cancer therapy and a safe and effective system for tumor-targeted delivery of microRNAs.

The need for non-invasive therapies capable of conserving drug efficiency and stability while having specific targetability against colorectal cancer (CRC), has made nanoparticles preferable vehicles and principal building blocks for the development of complex and multi-action anti-tumoral approaches. For that purpose, we herein report the production of a combinatory anti-tumoral nanotherapy using the production of a new targeting towards CRC lines. To do so, Magneto-fluorescent NANO3 nanoparticles were used as nanocarriers for a combination of the drugs doxorubicin (DOX) and ofloxacin (OFLO). NANO3 nanoparticles' surface was modified with two different targeting agents, a newly synthesized (anti-CA IX acetazolamide derivative (AZM-SH)) and a commercially available (anti-epidermal growth factor receptor (EGFR), Cetuximab). The cytotoxicity revealed that only DOX-containing nanosystems showed significant and even competitive cytotoxicity when compared to that of free DOX. Interestingly, surface modification with AZM-SH promoted an increased cellular uptake in the HCT116 cell line, surpassing even those functionalized with Cetuximab. The results show that the new target has high potential to be used as a nanotherapy agent for CRC cells, surpassing commercial targets. As a proof-of-concept, an oral administration form of NANO3 systems was successfully combined with Eudragit ® enteric coating and studied under extreme conditions.

The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.

Cancer-related opportunistic bacterial infections are one major barrier for successful clinical therapies, often correlated to the production of genotoxic factors and higher cancer incidence. Although dual anticancer and antimicrobial therapies are a growing therapeutic fashion, they still fall short when it comes to specific delivery and local action in in vivo systems. Nanoparticles are seen as potential therapeutic vectors, be it by means of their intrinsic antibacterial properties and effective delivery capacity, or by means of their repeatedly reported modulation and maneuverability. Herein we report on the production of a biocompatible, antimicrobial magneto-fluorescent nanosystem (NANO3) for the delivery of a dual doxorubicin-ofloxacin formulation against cancer-related bacterial infections. The drug delivery capacity, rendered by its mesoporous silica matrix, is confirmed by the high loading capacity and stimuli-driven release of both drugs, with preference for tumor-like acidic media. The pH-dependent emission of its surface fluorescent SiQDs, provides an insight into NANO3 surface behavior and pore availability, with the SiQDs working as pore gates. Hyperthermia induces heat generation to febrile temperatures, doubling drug release. NANO3-loaded systems demonstrate significant antimicrobial activity, specifically after the application of hyperthermia conditions. NANO3 structure and antimicrobial properties confirm their potential use in a future dual anticancer and antimicrobial therapeutical vector, due to their drug loading capacity and their surface availability for further modification with bioactive, targeting species.

We report herein the design of a strip-based rapid test utilizing bio-inspired hybrid nanomaterials for the in situ and at site detection of the drug scopolamine (SCP) using a smartphone for readout, allowing SCP identification in diluted saliva down to 40 nM in less than 15 min. For this purpose, we prepared a nanosensor based on mesoporous silica nanoparticles loaded with a fluorescent reporter (rhodamine B) and functionalized with bethanechol, a potent agonist of recombinant human muscarinic acetylcholine receptor M 2 (M 2 -AChR). M 2 -AChR interaction with the anchored bethanechol derivative leads to capping of the pores. The sensing mechanism relies on binding of SCP to M 2 -AChR resulting in pore opening and delivery of the entrapped rhodamine B reporter. Moreover, the material was incorporated into strips for lateral-flow assays coupled to smartphone readout, giving fast response time, good selectivity, and exceptional sensitivity. In an attempt to a mobile analytical test system for law enforcement services, we have also developed a dualplex lateral flow assay for SCP and 3,4-methylenedioxypyrovalerone (MDPV) also known as the so-called "cannibal drug".

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., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v / v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.

Among different hollow nanostructures, the preparation of hollow mesoporous silica nanoparticles (HMSNs) is still a hotspot research field due to their unique properties e.g., large pore sizes and volumes, high drug loading capacity, ease of surface modification, large surface area, and biodegradability. Herein, novel uniform HMSNs are prepared for the first time by a combination of heterogeneous oil-water biphase stratification and simple mono-, di-, and tri-valent etching reactions. The biphase stratification reaction allows self-assembly of reactants at the oil-water interface, while the subsequent step is designed for the efficient selective silica etching under mild conditions. We have studied the effect of cation's valence (NH 4 + , Ca 2+ , and Al 3+ ) on the silica etching reaction coupled with the biphase stratification reaction both in the absence and presence of the auxiliary pore expanded agent 1, 3, 5 trimethylbenzene (TMB). In the absence of TMB, the Brunauer-Emmett-Teller (BET) analysis confirms that Al 3+ creates materials with the largest pore size (18.0 nm), whereas the use of NH 4 + results in the largest pore volume (2.30 cm 3 /g). The pores generated using Ca 2+ and Al 3+ as silica etching agents have a volume 2.01 cm 3 /g and 2.05 cm 3 /g, respectively. Similar experiments in the presence of TMB leads to the formation of HMSN with larger pore sizes (24 nm and 21.5 nm) and volumes (2.70 cm 3 /g and 2.12 cm 3 , respectively, as etching agents. Drug loading capacity using Langmuir adsorption model indicate our hollow MSN material exhibit the high adsorbing DOX up to 558.23 mg per gram of nanoparticles in pH of 7.2. Furthermore, synthetized NPs exhibited high loading capacity for large protein and biomolecules such as BSA. Our findings confirmed that the charge density of cation has a critical role on selective silica etching in the preparation of HMSNs.3+ and Ca 2+ , respectively, as etching agents. Drug loading capacity using Langmuir adsorption model indicate our hollow MSN material exhibit the high adsorbing DOX up to 558.23 mg per gram of nanoparticles in pH of 7.2. Furthermore, synthetized NPs exhibited high loading capacity for large protein and biomolecules such as BSA. Our findings confirmed that the charge density of cation has a critical role on selective silica etching in the preparation of HMSNs., Competing Interests: Declaration of Competing Interest All the authors mentioned that there is no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

This work describes the assembly of a novel enzyme-controlled nanomachine operated through an AND Boolean logic gate for on-command delivery. The nanodevice was constructed on Au-mesoporous silica Janus nanoparticles capped with a thiol-sensitive gate-like molecular ensemble on the mesoporous face and functionalized with glutathione reductase on the gold face. This autonomous nanomachine employed NADPH and glutathione disulfide as input chemical signals, leading to the enzymatic production of reduced glutathione that causes the disruption of the gating mechanism on the mesoporous face and the consequent payload release as an output signal. The nanodevice was successfully used for the autonomous release of doxorubicin in HeLa cancer cells and RAW 264.7 macrophage cells.

Over the last years, respiratory diseases represent a clinical concern, being included among the leading causes of death in the world due to the lack of effective lung therapies, mainly ascribed to the pulmonary barriers affecting the delivery of drugs to the lungs. In this way, nanomedicine has arisen as a promising approach to overcome the limitations of current therapies for pulmonary diseases. The use of nanoparticles allows enhancing drug bioavailability at the target site while minimizing undesired side effects. Despite different approaches have been developed for pulmonary delivery of drugs, including the use of polymers, lipid-based nanoparticles, and inorganic nanoparticles, more efforts are required to achieve effective pulmonary drug delivery. This review provides an overview of the clinical challenges in main lung diseases, as well as highlighted the role of nanomedicine in achieving efficient pulmonary drug delivery. Drug delivery into the lungs is a complex process limited by the anatomical, physiological and immunological barriers of the respiratory system. We discuss how nanomedicine can be useful to overcome these pulmonary barriers and give insights for the rational design of future nanoparticles for enhancing lung treatments. We also attempt herein to display more in detail the potential of mesoporous silica nanoparticles (MSNs) as promising nanocarrier for pulmonary drug delivery by providing a comprehensive overview of their application in lung delivery to date while discussing the use of these particles for the treatment of respiratory diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1β cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1β levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

Benzene is a highly toxic aromatic hydrocarbon. Inhaling benzene can cause dizziness, vertigo, headaches, aplasia, mutations and, in the most extreme cases, cancer. Trans,trans-muconic acid (t,t-MA) is one of the metabolization products of benzene. Although different analytical methods have been reported for the determination of t,t-MA, these are often expensive, require trained personnel, are not suitable for on-site measurements, and use hazardous organic solvents. For these reasons, the development of reliable, selective and sensitive methods for rapid and in situ detection of t,t-MA are of importance. Addressing this challenge, a nanodevice for the selective and sensitive quantification of t,t-MA in urine is reported. The nanodevice used is achieved using mesoporous silica nanoparticles loaded with a dye reporter and capped with a dicopper(II) azacryptand. Pore opening and payload release is induced rapidly (10 min) and selectively with t,t-MA in urine, using a simple fluorimeter without sample pretreatment., (© 2020 Wiley-VCH GmbH.)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. In the last years, navitoclax has emerged as a possible treatment for TNBC. Nevertheless, rapid navitoclax resistance onset has been observed thorough Mcl-1 overexpression. As a strategy to overcome Mcl-1-mediated resistance, herein we present a controlled drug co-delivery system based on mesoporous silica nanoparticles (MSNs) targeted to TNBC cells. The nanocarrier is loaded with navitoclax and the Mcl-1 inhibitor S63845 and capped with a MUC1-targeting aptamer (apMUC1-MSNs(Nav/S63845)). The apMUC1-capped nanoparticles effectively target TNBC cell lines and successfully induce apoptosis, overcoming navitoclax resistance. Moreover, navitoclax encapsulation protects platelets against apoptosis. These results point apMUC1-gated MSNs as suitable BH3 mimetics nanocarriers in the targeted treatment of MUC1-expressing TNBC., (© 2020 Wiley-VCH GmbH.)

A bio-inspired nanodevice for the selective and sensitive fluorogenic detection of 3,4-methylenedioxypyrovalerone (MDPV), usually known as Cannibal drug, is reported. The sensing nanodevice is based on mesoporous silica nanoparticles (MSNs), loaded with a fluorescent reporter (rhodamine B), and functionalized on their external surface with a dopamine derivative ( 3 ), which specifically interacts with the recombinant human dopamine transporter (DAT), capping the pores. In the presence of MDPV, DAT detaches from the MSNs consequently, causing rhodamine B release and allowing drug detection. The nanosensor shows a detection limit of 5.2 μM, and it is able to detect the MDPV drug both in saliva and blood plasma samples.

A biocomputing strategy implemented in hybrid nanocarriers for controlled cargo delivery is described. The nanodevice consists of enzyme-functionalized Janus Au-mesoporous silica nanoparticles, which behave as an electronic demultiplexer (DEMUX). The nanocarrier is capable of reading molecular information from the environment (lactose) and selecting one of two possible outputs (galactose production or 4-methylumbellilferone release and activation) depending on the presence of an addressing input (NAD + ).

The characteristics and electromechanical properties of conductive polymers together to their biocompatibility have boosted their application as a suitable tool in regenerative medicine and tissue engineering. However, conducting polymers as drug release materials are far from being ideal. A possibility to overcome this drawback is to combine conducting polymers with on-command delivery particles with inherent high-loading capacity. In this scenario, we report here the preparation of conduction polymers containing gated mesoporous silica nanoparticles (MSN) loaded with a cargo that is delivered on command by electro-chemical stimuli increasing the potential use of conducting polymers as controlled delivery systems. MSNs are loaded with Rhodamine B (Rh B), anchored to the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)], functionalized with a bipyridinium derivative and pores are capped with heparin (P3) by electrostatic interactions. P3 releases the entrapped cargo after the application of -640 mV voltage versus the saturated calomel electrode (SCE). Pore opening in the nanoparticles and dye delivery is ascribed to both (i) the reduction of the grafted bipyridinium derivative and (ii) the polarization of the conducting polymer electrode to negative potentials that induce detachment of positively charged heparin from the surface of the nanoparticles. Biocompatibility and cargo release studies were carried out in HeLa cells cultures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nanoparticle-cell-nanoparticle communication by stigmergy was demonstrated using two capped nanodevices. The first community of nanoparticles (i.e.S(RA)IFN) is loaded with 9-cis-retinoic acid and capped with interferon-γ, whereas the second community of nanoparticles (i.e.S(sulf)PIC) is loaded with sulforhodamine B and capped with poly(I:C). The uptake of S(RA)IFN by SK-BR-3 breast cancer cells enhanced the expression of TLR3 receptor facilitating the subsequent uptake of S(sulf)PIC and cell killing.

A novel nanomachine for dual and sequential delivery of two different compounds was developed by grafting a thiol group and a pH sensitive β-cyclodextrin-based gate-like ensemble on acetylcholinesterase-modified Au-mesoporous silica Janus nanoparticles.

One appealing concept in the field of hybrid materials is related to the design of gated materials. These materials are prepared in such a way that the release of chemical or biochemical species from voids of porous supports to a solution is triggered upon the application of external stimuli. Such gated materials are mainly composed of two subunits: i) a porous inorganic scaffold in which a cargo is stored, and ii) certain molecular or supramolecular entities, grafted onto the external surface, that can control mass transport from the interior of the pores. On the basis of this concept, a large number of examples are developed in the past ten years. A comprehensive overview of gated materials used in drug delivery applications in in vivo models from 2016 to date is thus given here., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

: Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN ) , of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.

Here we report functional stimulus-responsive nanomotors based on Janus Au-mesoporous silica nanoparticles capable of self-propelling via the biocatalytic conversion of chemical fuel, that read information from the environment (the presence of glutathione) and accordingly deliver a cargo.

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy) 3 ]Cl 2 (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy) 3 ]Cl 2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to "sense" the environment and deliver the payload on demand in response to predefined stimuli.

The construction of communication models at the micro-/nanoscale involving abiotic nanodevices and living organisms has the potential to open a wide range of applications in biomedical and communication technologies. However, this area remains almost unexplored. Herein, we report, as a proof of concept, a stimuli-responsive interactive paradigm of communication between yeasts (as a model microorganism) and enzyme-controlled Janus Au-mesoporous silica nanoparticles. In the presence of the stimulus, the information flows from the microorganism to the nanodevice, and then returns from the nanodevice to the microorganism as a feedback., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 ± 8.1 nm). From the isotherm curve, a specific surface area of 872 m 2 /g was estimated along with a pore volume of 0.85 cm 3 /g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The use of nanosystems as diagnosing and therapy systems is increasing each year. There are several nanosystems available and the most prominent ones are: mesoporous silica, nanoemulsion and polymeric nanoparticles. With characteristics like low toxicology, and easy-producing process they have advantages when compared with the traditional system used, as they show specific targeting, controlled release, and higher penetration. In this study we tested three different nanocarriers (polymeric nanoparticles, nanoemulsion and mesoporous silica) containing phthalocyanineas possible PDT drugs (nanodrugs). They were tested in vitro and in vivo: cells and healthy mice, respectively, in order to understand the biological behavior and reach the initial conclusions. The results in cells showed that a dose response was observed with different concentrations of the three nanocarriers. The results in animal showed that all nanosystems have potential for application in PDT, since they were able to produce a visible effect in healthy animals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O and the external surface was functionalized with an azo derivative 1 (bearing a carbamate linkage) yielding solid S1 . Aqueous suspensions of S1 at pH 7.4 showed negligible safranin O release due to the presence of the bulky azo derivative attached onto the external surface of the inorganic scaffold. However, in the presence of sodium dithionite (azoreductive agent), a remarkable safranin O delivery was observed. At acidic pH, a certain safranin O release from S1 was also found. The pH-triggered safranin O delivery was ascribed to the acid-induced hydrolysis of the carbamate moiety that linked the bulky azo derivatives onto the mesoporous inorganic magnetic support. The controlled release behavior of S1 was also tested using a model that simulated the gastro intestinal tract., Competing Interests: The authors declare no conflict of interest.

Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Acα interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Acα interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safranin O (S2) or with C9h peptide (S4) and functionalized with ϵ-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safranin O or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50 %) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Acα interaction., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Breast cancer is women's most common type of cancer, with a global rate of over 522,000 deaths per year. One of the main problems related to breast cancer relies in the early detection, as the specialized treatment. In this direction was developed, characterized and tested in vivo a smart delivery system, based on radiolabelled magnetic core mesoporous silica doped with trastuzumab as intralesional nanodrug for breast cancer imaging and possible therapy. The results showed that nanoparticles had a size of 58.9 ± 8.1 nm, with specific surface area of 872 m 2 /g and pore volume of 0.85 cm 3 /g with a pore diameter of 3.15 nm. The magnetic core mesoporous silica was efficiently labelled with 99mTc (97.5% ±0.8) and doped >98%. The cytotoxicity assay, demonstrated they are safe to use. The data were corroborated with the IC50 result of: 829.6 µg ± 43.2. The biodistribution showed an uptake by the tumour of 7.5% (systemic via) and 97.37% (intralesional) with less than 3% of these nanoparticles absorbed by healthy tissues. In a period 6-h post-injection, no barrier delimited by the tumour was crossed, corroborating the use as intralesional nanodrug.

Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.

Whether in the cosmetic or as therapeutic, the use of nanoparticles has been increasing and taking on global proportion. However, there are few studies about the physical potential of long-term use or use in special conditions such as chronic, AIDS, pregnant women and other special health circumstances. In this context, the study of the mutagenicity and the transplacental passage represents an important and reliable model for the primary evaluation of potential health risks, especially maternal and child health. In this study we performed mutagenicity, cytotoxic and transplacental evaluation of magnetic core mesoporous silica nanoparticles, radiolabeled with 99m Tc for determination of toxicogenic and embryonic/fetuses potential risk in animal model. Magnetic core mesoporous silica nanoparticles were produced and characterized by obtaining nanoparticles with a size of (58.9 ± 8.1 nm) in spherical shape and with intact magnetic core. The 99 m Tc radiolabeling process demonstrated high efficacy and stability in 98% yield over a period of 8 hours of stability. Mutagenicity assays were performed using Salmonella enteric serovar Typhimurium standard strains TA98, TA100 and TA102. Cytotoxicity assays were performed using WST-1. The transplacental evaluation assays were performed using the in vivo model with rats in two periods: embryonic and fetal stage. The results of both analyzes corroborate that the nanoparticles can i) generate DNA damage; ii) generate cytotoxic potential and iii) cross the transplantation barrier in both stages and bioaccumulates in both embryos and fetuses. The results suggest that complementary evaluations should be conducted in order to attest safety, efficacy and quality of nanoparticles before unrestricted approval of their use.

Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with 99m Tc (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The development of easy and affordable methods for the detection of cyanide is of great significance due to the high toxicity of this anion and the potential risks associated with its pollution. Herein, optical detection of cyanide in water has been achieved by using a hybrid organic-inorganic nanomaterial. Mesoporous silica nanoparticles were loaded with [Ru(bipy) 3 ] 2+ , functionalized with macrocyclic nickel(II) complex subunits, and capped with a sterically hindering anion (hexametaphosphate). Cyanide selectively induces demetallation of nickel(II) complexes and the removal of capping anions from the silica surface, allowing the release of the dye and the consequent increase in fluorescence intensity. The response of the capped nanoparticles in aqueous solution is highly selective and sensitive towards cyanide with a limit of detection of 2 μm., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Two different acetylcholinesterase (AChE)-capped mesoporous silica nanoparticles (MSNs), S1-AChE and S2-AChE, were prepared and characterized. MSNs were loaded with rhodamine B and the external surface was functionalized with either pyridostigmine derivative P1 (to yield solid S1) or neostigmine derivative P2 (to obtain S2). The final capped materials were obtained by coordinating grafted P1 or P2 with AChE's active sites (to give S1-AChE and S2-AChE, respectively). Both materials were able to release rhodamine B in the presence of diisopropylfluorophosphate (DFP) or neostigmine in a concentration-dependent manner via the competitive displacement of AChE through DFP and neostigmine coordination with the AChE's active sites. The responses of S1-AChE and S2-AChE were also tested with other enzyme inhibitors and substrates. These studies suggest that S1-AChE nanoparticles can be used for the selective detection of nerve agent simulant DFP and paraoxon., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Acute inflammation is a protective response of the body to harmful stimuli, such as pathogens or damaged cells. However, dysregulated inflammation can cause secondary damage and could thus contribute to the pathophysiology of many diseases. Inflammasomes, the macromolecular complexes responsible for caspase-1 activation, have emerged as key regulators of immune and inflammatory responses. Therefore, modulation of inflammasome activity has become an important therapeutic approach. Here we describe the design of a smart nanodevice that takes advantage of the passive targeting of nanoparticles to macrophages and enhances the therapeutic effect of caspase-1 inhibitor VX-765 in vivo. The functional hybrid systems consisted of MCM-41-based nanoparticles loaded with anti-inflammatory drug VX-765 (S2-P) and capped with poly-L-lysine, which acts as a molecular gate. S2-P activity has been evaluated in cellular and in vivo models of inflammation. The results indicated the potential advantage of using nanodevices to treat inflammatory diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cargo delivery from mesoporous silica nanoparticles loaded with sulforhodamine B and capped with a difluoroboron-dipyrromethene (BODIPY) derivative was triggered by a NO 2 -induced oxidative process.

Mesoporous silica nanoparticles (MSNs) are highly attractive as supports in the design of controlled delivery systems that can act as containers for the encapsulation of therapeutic agents, overcoming common issues such as poor water solubility and poor stability of some drugs and also enhancing their bioavailability. In this context, we describe herein the development of polyglutamic acid (PGA)-capped MSNs that can selectively deliver rhodamine B and doxorubicin. PGA-capped MSNs remain closed in an aqueous environment, yet they are able to deliver the cargo in the presence of pronase because of the hydrolysis of the peptide bonds in PGA. The prepared solids released less than 20% of the cargo in 1 day in water, whereas they were able to reach 90% of the maximum release of the entrapped guest in ca. 5 h in the presence of pronase. Studies of the PGA-capped nanoparticles with SK-BR-3 breast cancer cells were also undertaken. Rhodamine-loaded nanoparticles were not toxic, whereas doxorubicin-loaded nanoparticles were able to efficiently kill more than 90% of the cancer cells at a concentration of 100 μg/mL.

We report herein the design of a stimulus-programmed pulsatile delivery system for sequential cargo release based on the use of a lactose-modified esterase as a capping agent in phenylboronic acid functionalized mesoporous silica nanoparticles. The dual-release mechanism was based on the distinct stability of the cyclic boronic acid esters formed with lactose residues and the long naturally occurring glycosylation chains in the modified neoglycoenzyme. Cargo delivery in succession was achieved using glucose and ethyl butyrate as triggers.

Multidisciplinary research at the forefront of the field of hybrid materials has paved the way to the development of endless examples of smart devices. One appealing concept in this fertile field is related to the design of gated materials. These are constructed for finely tuning the delivery of chemical or biochemical species from voids of porous supports to a solution in response to predefined stimuli. Such gated materials are composed mainly of two subunits: (i) a porous inorganic support in which a cargo is loaded and (ii) certain molecular or supramolecular entities, generally grafted onto the external surface, which can control mass transport from pores. On the basis of this concept, a large number of imaginative examples have been developed. This review intends to be a comprehensive analysis of papers published until 2014 on hybrid mesoporous gated materials. The molecules used as gates, the opening mechanisms, and controlled release behavior are detailed. We hope this review will not only help researchers who work in this field but also may open the minds of related ones to develop new advances in this fertile research area.

We describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. Our results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)