The treatment of diseases that affect the central nervous system (CNS) represents a great research challenge due to the restriction imposed by the blood–brain barrier (BBB) to allow the passage of drugs into the brain. However, the use of modified nanomedicines engineered with different ligands that can be recognized by receptors expressed in the BBB offers a favorable alternative for this purpose. In this work, a BBB-penetrating peptide, angiopep-2 (Ang–2), was conjugated to poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles through pre- and post-formulation strategies. Then, their ability to cross the BBB was qualitatively assessed on an animal model. Proof-of-concept studies with fluorescent and confocal microscopy studies highlighted that the brain-targeted PLGA nanoparticles were able to cross the BBB and accumulated in neuronal cells, thus showing a promising brain drug delivery system.

The accumulation of amyloid β (Aβ) triggers a cascade of toxic events in Alzheimer’s disease (AD). The KLVFF peptide can interfere with Aβ aggregation. However, the peptide suffers from poor bioavailability and the inability to cross the blood–brain barrier. In this work, we study the possibility of adopting nanomedicine to overcome KLVFF limits in biodistribution. We produced new engineered polymeric nanoparticles (NPs), and we evaluated the cellular toxicity of these NPs and validated that KVLFF peptides released by NPs show the same promising effects on AD pathology. Our results revealed the successful generation of KVLFF loaded NPs that, without significant effects on cell heath, are even more potent in reversing Aβ-induced pathologies compared to the free peptide. Therefore, NPs will significantly advance KVLFF treatment as a therapeutic option for AD.

The identification of effective pharmacological tools for Alzheimer’s disease (AD) represents one of the main challenges for therapeutic discovery. Due to the variety of pathological processes associated with AD, a promising route for pharmacological intervention involves the development of new chemical entities that can restore cellular homeostasis. To investigate this strategy, we designed and synthetized SG2, a compound related to the thyroid hormone thyroxine, that shares a pleiotropic activity with its endogenous parent compound, including autophagic flux promotion, neuroprotection, and metabolic reprogramming. We demonstrate herein that SG2 acts in a pleiotropic manner to induce recovery in a C. elegans model of AD based on the overexpression of Aβ42 and improves learning abilities in the 5XFAD mouse model of AD. Further, in vitro ADME-Tox profiling and toxicological studies in zebrafish confirmed the low toxicity of this compound, which represents a chemical starting point for AD drug development.

Cancer treatment, particularly chemotherapy, requires balancing efficacy and toxicity. Although traditional monitoring methods can lead to suboptimal outcomes, emerging implantable chemical sensors can complement them by providing precise, real-time drug monitoring at tumor sites, although the technology remains in its early stages. Here, we introduce an ultrathin, bioresorbable implantable biosensor for real-time doxorubicin monitoring in vivo with high spatiotemporal resolution. The sensor amplifies the drug’s fluorescence, enabling successful tracking of doxorubicin through the skin in live mice following intravenous injection. When paired with a reusable electronic patch, the biosensor facilitates seamless data collection and wireless transmission. A 3-month biocompatibility study, including systemic toxicity assessments, histological and blood analyses, confirms complete biodegradation with no observed toxicity. By directly measuring chemotherapeutic drug levels in tissues over time, our sensor enhances traditional monitoring methods, enabling clinicians to optimize dosing during cancer treatment and reduce the risk of locoregional recurrence following tumor removal.

Implantable sensors are redefining real‐time, continuous physiological monitoring and hold great promise for personalized medicine. Yet, their clinical application is often hindered by the lack of effective encapsulation materials that simultaneously ensure environmental exposure and protect sensor components, thereby preserving signal fidelity. Although hydrogel‐based systems offer promising features such as biological tissue‐like mechanics and biocompatibility, their use as sensor coatings remains limited. Notably, despite growing interest in bioresorbable implant technologies, few coating systems offer controlled, on‐demand degradability, which represents a key requirement to avoid possible misalignment between coating dissolution rate and sensor lifetime. Here, we present a thermoresponsive hydrogel, consisting of methylcellulose, polyethylene glycol and polyacrylic acid (MC/PEG/PAA), demonstrating its high suitability as a transient encapsulating coating. The system, assembled by physical cross‐linking without using toxic reagents, and extensively characterized in terms of thermal responsiveness, swelling behavior, stability, and mechanical performance, exhibited reversible dissolution upon a mild temperature drop (from ≈37°C to ≈25°C), which was conveniently used to easily enable its degradation under physiological conditions. The hydrogel ability to act as a coating was demonstrated via the encapsulation of a fluorescent model device, confirming its optical transparency and signal‐transmission capability. In vitro studies indicated the hydrogel potential to mitigate inflammatory response, while in vivo biocompatibility, assessed in mice, revealed no signs of systemic toxicity or behavioral changes post‐implantation. Additionally, the hydrogel exhibited safe in vivo biodegradation upon a slight local temperature decrease, completely dissolving within few minutes. The developed coating, integrating good optical transparency, ease of fabrication, and in vivo safety with on‐demand, controllable degradation upon an external low‐temperature stimulus, represents a substantial advancement toward next‐generation bioresorbable implantable devices and paves the way for driving successful transformation in the field.