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This research is based on the incorporation of the methanolic extract of the Usnea ghattensis into poly (caprolactone) (PCL) nanofibers (NFs) to investigate the capacity in reducing reactive oxygen species (ROS). PCL-NFs were fabricated by the electrospinning technique and are investigated as potential dressing material focused on the release of usnic acid (PCL-USNIC NFs), and its encapsulation efficiency and kinetic release were analyzed by high performance liquid chromatography (HPLC). This investigation was performed by analyzing the usnic acid concentration as a function of the distance from the mat center point. The kinetic release analysis is also developed with the usnea ghattensis extract (PCL-USNEA NFs), performing a metabolomic analysis of the released molecules as a function of time by nuclear magnetic resonance (NMR). Usnic acid was revealed as the most relevant compound together with other molecules, such as sucrose, mannitol, arabitol or glycerol that generate a positive matrix effect on the release of usnic acid. Finally, we analize the cytotoxicity and the neuroprotective effect of PCL-USNEA and PCL-USNIC NFs using a human neuroblastoma cell line model. Negligible toxicity was appreciated for both polymeric systems, showing high protective effects in presence of highly oxidative environment (e.g. in presence of H 2 O 2 )., 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 Elsevier B.V. All rights reserved.)

Targeting epigenetic mechanisms has emerged as a potential therapeutic approach for the treatment of kidney diseases. Specifically, inhibiting the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1 has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, its clinical translation faces challenges due to issues with poor pharmacokinetics and side effects. Here, we developed engineered liposomes loaded with JQ1 with the aim of enhancing kidney drug delivery and reducing the required minimum effective dose by leveraging cargo protection. These liposomes efficiently encapsulated JQ1 in both the membrane and core, demonstrating superior therapeutic efficacy compared to freely delivered JQ1 in a mouse model of kidney ischemia-reperfusion injury. JQ1-loaded liposomes (JQ1-NPs) effectively targeted the kidneys and only one administration, one-hour after injury, was enough to decrease the immune cell (neutrophils and monocytes) infiltration to the kidney-an early and pivotal step to prevent damage progression. By inhibiting BRD4, JQ1-NPs suppress the transcription of pro-inflammatory genes, such as cytokines (il-6) and chemokines (ccl2, ccl5). This success not only improved early the kidney function, as evidenced by decreased serum levels of BUN and creatinine in JQ1-NPs-treated mice, along with reduced tissue expression of the damage marker, NGAL, but also halted the production of extracellular matrix proteins (Fsp-1, Fn-1, α-SMA and Col1a1) and the fibrosis development. In summary, this work presents a promising nanotherapeutic strategy for AKI treatment and its progression and provides new insights into renal drug delivery., 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 Masson SAS.)

The COVID-19 pandemic has taught us valuable lessons, especially the urgent need for a widespread, rapid and sensitive diagnostic tool. To this, the integration of bidimensional nanomaterials, particularly graphene, into point-of-care biomedical devices is a groundbreaking strategy able to potentially revolutionize the diagnostic landscape. Despite advancements in the fabrication of these biosensors, the relationship between their surface biofunctionalization and sensing performance remains unclear. Here, we demonstrate that the combination of careful sensor fabrication and its precise surface biofunctionalization is crucial for exalting the sensing performances of 2D biosensors. Specifically, we have biofunctionalized Graphene Field-Effect Transistor (GFET) sensors surface through different biochemical reactions to promote either random/heterogeneous or oriented/homogeneous immobilization of the Anti-SARS-CoV-2 spike protein antibody. Each strategy was thoroughly characterized by in-silico simulations, physicochemical and biochemical techniques and electrical characterization. Subsequently, both biosensors were tested in the label-free direct titration of SARS-CoV-2 virus in simulated clinical samples, avoiding sample preprocessing and within short timeframes. Remarkably, the oriented GFET biosensor exhibited significantly enhanced reproducibility and responsiveness, surpassing the detection sensitivity of conventional non-oriented GFET by more than twofold. This breakthrough not only involves direct implications for COVID-19 surveillance and next pandemic preparedness but also clarify an unexplored mechanistic dimension of biosensor research utilizing 2D-nanomaterials., 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.)

Among the most harmful tumors detected in the human body, such as breast, colon, brain or pancreas, breast (BC) and colorectal cancer (CRC) are the first and third most frequent cancer worldwide, respectively. The current existing chemotherapeutic treatments present serious side effects due to their intravenous administration can induce cytotoxicity in healthy cells. Thus, new treatment methods based on drug-loaded polymeric nanofibers (NFs) have gained significant potential for their use in localized cancer chemotherapy. Here, a deep in vitro comparative analysis between maslinic acid (MA) and a tyramine-maslinic acid (TMA) derivative is initially performed. This analysis includes a proliferation, and a cell cycle assay, and a genotoxicity, antiangiogenic and apoptosis study. Then, the TMA derivative has been incorporated into electrospun polymeric NFs obtaining an implantable dressing material with antitumor activity. Two types of patches containing TMA-loaded polymeric NFs of poly(caprolactone) (PCL), and a mixture of polylactic acid/poly(4-vinylpyridine) (PLA/PVP) were fabricated by the electrospinning technique. The characterization of the drug-loaded NFs showed an encapsulation capacity of 0.027 mg TMA/mg PCL and 0.024 mg TMA/mg PLA/PVP. Then, the cytotoxic activity of both polymeric systems was tested in CRC (T84), BC (MCF-7) and a no tumor (L929) cell lines exposed to TMA-loaded NFs and blank NFs for 48 h. Moreover, cell cycle assay, genotoxicity, angiogenesis and apoptosis tests were carried out to study the mechanism of action of TMA. Blank NFs showed no-toxicity in all cell lines tested and both drug-loaded NFs significantly reduced cell proliferation (relative proliferation of ≈44 % and ≈25 % respectively). Therefore, TMA was less genotoxic than maslinic acid (MA), and reduced VEGFA expression in MCF-7 cells (1.32 and 2.12-fold for MA and TMA respectively). These results showed that TMA-loaded NFs could constitute a promising biocompatible and biodegradable nanoplatform for the local treatment of solid tumors such as CRC or BC., 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.)

A new series of theranostic silica materials based on fibrous silica particles acting as nanocarriers of two different cytotoxic agents, namely, chlorambucil and an organotin metallodrug have been prepared and structurally characterized. Besides the combined therapeutic activity, these platforms have been decorated with a targeting molecule (folic acid, to selectively target triple negative breast cancer) and a molecular imaging agent (Alexa Fluor 647, to enable their tracking both in vitro and in vivo). The in vitro behaviour of the multifunctional silica systems showed a synergistic activity of the two chemotherapeutic agents in the form of an enhanced cytotoxicity against MDA-MB-231 cells (triple negative breast cancer) as well as by a higher cell migration inhibition. Subsequently, the in vivo applicability of the siliceous nanotheranostics was successfully assessed by observing with in vivo optical imaging techniques a selective tumour accumulation (targeting ability), a marked inhibition of tumour growth paired to a marked antiangiogenic ability after 13 days of systemic administration, thus, confirming the enhanced theranostic activity. The systemic nanotoxicity was also evaluated by analyzing specific biochemical markers. The results showed a positive effect in form of reduced cytotoxicity when both chemotherapeutics are administered in combination thanks to the fibrous silica nanoparticles. Overall, our results confirm the promising applicability of these novel silica-based nanoplatforms as advanced drug-delivery systems for the synergistic theranosis of triple negative breast cancer., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ag 2 S nanoparticles are near-infrared (NIR) probes providing emission in a specific spectral range (~1200 nm), and superparamagnetic iron oxide nanoparticles (SPION) are colloidal systems able to respond to an external magnetic field. A disadvantage of Ag 2 S NPs is the attenuated luminescent properties are reduced in aqueous media and human fluids. Concerning SPION, the main drawback is the generation of undesirable clusters that reduce particle stability. Here, we fabricate biocompatible hybrid nanosystems combining Ag 2 S NPs and SPION by the electrospraying technique for drug delivery purposes. These nanostructures are composed of poly(lactic-co-glycolic acid) (PLGA) as the polymeric matrix in connection with both Ag 2 S NPs and SPIONs. Initially, we fabricate a hybrid colloidal nanosystem composed of Ag 2 S NPs in connection with PLGA (PLGA@Ag 2 S) by three different routes, showing good photoluminescent (PL) properties with relatively high average decay times. Then, we incorporate SPIONs, obtaining a PLGA polymeric matrix containing both Ag 2 S NPs and SPION (PLGA@Ag 2 S@SPION). Interestingly, in this hybrid system, the location of Ag 2 S NPs and SPIONs depends on the synthesis route performed during electrospraying. After a detailed characterization, we demonstrate the encapsulation and release capabilities, obtaining the kinetic release using a model chemotherapeutic drug (maslinic acid). Finally, we perform in vitro cytotoxicity assays using drug-loaded hybrid systems against several tumor cell lines.

The treatment of skin wounds poses significant clinical challenges, including the risk of bacterial infection. In particular due to its antimicrobial and tissue regeneration abilities chitosan (a polymeric biomaterial obtained by the deacetylation of chitin) has received extensive attention for its effectiveness in promoting skin wound repair. On the other hand, due to their intrinsic characteristics, metal nanoparticles (e.g., silver (Ag), gold (Au) or iron oxide (Fe 3 O 4 )) have demonstrated therapeutic properties potentially useful in the field of skin care. Therefore, the combination of these two promising materials (chitosan plus metal oxide NPs) could permit the achievement of a promising nanohybrid with enhanced properties that could be applied in advanced skin treatment. In this work, we have optimized the synthesis protocol of chitosan/metal hybrid nanoparticles by means of a straightforward synthetic method, ionotropic gelation, which presents a wide set of advantages. The synthesized hybrid NPs have undergone to a full physicochemical characterization. After that, the in vitro antibacterial and tissue regenerative activities of the achieved hybrids have been assessed in comparison to their individual constituent. As result, we have demonstrated the synergistic antibacterial plus the tissue regeneration enhancement of these nanohybrids as a consequence of the fusion between chitosan and metallic nanoparticles, especially in the case of chitosan/Fe 3 O 4 hybrid nanoparticles.

Cancer is the second leading cause of death in the world, which is why it is so important to make an early and very precise diagnosis to obtain a good prognosis. Thanks to the combination of several imaging modalities in the form of the multimodal molecular imaging (MI) strategy, a great advance has been made in early diagnosis, in more targeted and personalized therapy, and in the prediction of the results that will be obtained once the anticancer treatment is applied. In this context, magnetic nanoparticles have been positioned as strong candidates for diagnostic agents as they provide very good imaging performance. Furthermore, thanks to their high versatility, when combined with other molecular agents (for example, fluorescent molecules or radioisotopes), they highlight the advantages of several imaging techniques at the same time. These hybrid nanosystems can be also used as multifunctional and/or theranostic systems as they can provide images of the tumor area while they administer drugs and act as therapeutic agents. Therefore, in this review, we selected and identified more than 160 recent articles and reviews and offer a broad overview of the most important concepts that support the synthesis and application of multifunctional magnetic nanoparticles as molecular agents in advanced cancer detection based on the multimodal molecular imaging approach.

Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph 3 Sn{SCH 2 CH 2 CH 2 Si(OMe) 3 } (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.