Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard.

Optimized Synthesis of Poly(Lactic Acid) Nanoparticles for the Encapsulation of Flutamide.

Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.

Dual-Crosslinked Dynamic Hydrogel Incorporating {Mo154 } with pH and NIR Responsiveness for Chemo-Photothermal Therapy.

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo154 } is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo154 } and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo154 }. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo154 }-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.

Cellulose Nanocrystals/Chitosan-Based Nanosystems: Synthesis, Characterization, and Cellular Uptake on Breast Cancer Cells.

Cellulose nanocrystals (CNCs) are elongated biobased nanostructures with unique characteristics that can be explored as nanosystems in cancer treatment. Herein, the synthesis, characterization, and cellular uptake on folate receptor (FR)-positive breast cancer cells of nanosystems based on CNCs and a chitosan (CS) derivative are investigated. The physical adsorption of the CS derivative, containing a targeting ligand (folic acid, FA) and an imaging agent (fluorescein isothiocyanate, FITC), on the surface of the CNCs was studied as an eco-friendly methodology to functionalize CNCs. The fluorescent CNCs/FA-CS-FITC nanosystems with a rod-like morphology showed good stability in simulated physiological and non-physiological conditions and non-cytotoxicity towards MDA-MB-231 breast cancer cells. These functionalized CNCs presented a concentration-dependent cellular internalization with a 5-fold increase in the fluorescence intensity for the nanosystem with the higher FA content. Furthermore, the exometabolic profile of the MDA-MB-231 cells exposed to the CNCs/FA-CS-FITC nanosystems disclosed a moderate impact on the cells' metabolic activity, limited to decreased choline uptake and increased acetate release, which implies an anti-proliferative effect. The overall results demonstrate that the CNCs/FA-CS-FITC nanosystems, prepared by an eco-friendly approach, have a high affinity towards FR-positive cancer cells and thus might be applied as nanocarriers with imaging properties for active targeted therapy.

Multifunctional hybrid structures made of open-cell aluminum foam impregnated with cellulose/graphene nanocomposites.

This work focuses on exploring combinations of disintegrated bacterial cellulose nanofibres (BC) with graphene oxide (GO) (reduced and non-reduced) and phase change materials (PCMs) prepared in the form of foam-like structures. The presence of GO remarkable improves the fire-retardancy and provides dimensional stability to the foams while PCMs gives thermal energy storage capacity. The foams were exposed to methyltrimethoxysilane (MTMS) vapour to become hydrophobic which was confirmed by measuring water absorption capacity and water contact angle. To extend the multifunctionality of these nanocomposite foams, a selected composition was impregnated into an open-cell aluminium foam creating a hybrid structure (Al-BC/GO) with higher mechanical properties (increase in stress of 100 times) and high sound absorption coefficient (near 1 between 1000-4000 Hz). The low thermal conductivity confirms that this hybrid structure is a thermal insulator. These advantages highlight the potential applications of the proposed materials e.g. construction, automotive and aeronautical sectors.

One-Minute Synthesis of Size-Controlled Fucoidan-Gold Nanosystems: Antitumoral Activity and Dark Field Imaging.

Gold nanoparticles (AuNPs) are one of the most studied nanosystems with great potential for biomedical applications, including cancer therapy. Although some gold-based systems have been described, the use of green and faster methods that allow the control of their properties is of prime importance. Thus, the present study reports a one-minute microwave-assisted synthesis of fucoidan-coated AuNPs with controllable size and high antitumoral activity. The NPs were synthesized using a fucoidan-enriched fraction extracted from Fucus vesiculosus, as the reducing and capping agent. The ensuing monodispersed and spherical NPs exhibit tiny diameters between 5.8 and 13.4 nm for concentrations of fucoidan between 0.5 and 0.05% (w/v), respectively, as excellent colloidal stability in distinct solutions and culture media. Furthermore, the NPs present antitumoral activity against three human tumor cell lines (MNT-1, HepG2, and MG-63), and flow cytometry in combination with dark-field imaging confirmed the cellular uptake of NPs by MG-63 cell line.

NMR Metabolomics Reveals Metabolism-Mediated Protective Effects in Liver (HepG2) Cells Exposed to Subtoxic Levels of Silver Nanoparticles.

The expansion of biomedical and therapeutic applications of silver nanoparticles (AgNPs) raises the need to further understand their biological effects on human cells. In this work, NMR metabolomics has been applied to reveal the metabolic effects of AgNPs toward human hepatoma (HepG2) cells, which are relevant with respect to nanoparticle accumulation and detoxification. Cellular responses to widely disseminated citrate-coated AgNPs (Cit30) and to emergent biogenic AgNPs prepared using an aqueous plant extract as reducing and stabilizing agent (GS30) have been compared with a view to assess the influence of nanoparticle coating on the metabolic effects produced. Subtoxic concentrations (IC5 and IC20) of both nanoparticle types caused profound changes in the cellular metabolome, suggesting adaptations in energy production processes (glucose metabolism and the phosphocreatine system), antioxidant defenses, protein degradation and lipid metabolism. These signatures were proposed to reflect mainly metabolism-mediated protective mechanisms and were found to be largely common to Cit30 and GS30 AgNPs, although differences in the magnitude of response, not captured by conventional cytotoxicity assessment, were detected. Overall, this study highlights the value of NMR metabolomics for revealing subtoxic biological effects and helping to understand cell-nanomaterial interactions.