Breast cancer stands as the primary cancer affecting women and the second most prevalent cause of cancer-related fatalities in developed nations. Consequently, there is a pressing demand for the advancement of therapeutic strategies that can be seamlessly integrated into clinical applications. We investigated the effectiveness of an encapsulation and decoration strategy employing biodegradable and biocompatible carriers together with 3D collagen-based culture models. Envisioning the use of nano delivery systems for localized regional release, we explored the feasibility of a light-controlled drug release, assisted by optical fibers. PLGA nanoparticles loaded or decorated with trastuzumab (TZ) were synthesized via a double emulsion protocol and characterized by dynamic light scattering, surface plasmon resonance, transmission electron microscopy, atomic force microscopy, and Fourier transform infrared spectroscopy. In vitro biological evaluation was then performed on HER2-positive breast cancer cell line BT-474, examining the effect of nanoformulations on cell viability in 2D and 3D collagen scaffold culture models. Cell cycle, apoptosis, cell morphology and distribution and protein expression were analyzed. Finally, a core-offset optical fiber was fabricated and particles release was studied in vitro using light in batch and microfluidic tests. The nanoparticles displayed uniform and spherical shape, maintaining stability in DMEM for up to seven days. The successful immobilization of TZ was verified. In vitro trials with BT-474 cells in 2D and 3D models revealed that poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with TZ demonstrated similar or superior biological activity compared to free TZ. Notably, PLGA functionalized with TZ both internally and on the surface exhibited the highest effectiveness in terms of cell viability, increase of apoptosis markers, and inducing cell quiescence. This affirms the pivotal role of PLGA nanoparticles in preserving the integrity of TZ and enhancing its targeted delivery. Furthermore, we propose a breakthrough fiber-optic technology for the less invasive local delivery of PLGA-based nanocarriers that can be effectively used in clinical practice. In conclusion our studies lay the foundation for future advancements in alternative therapeutic tools for localized breast cancer treatment. The integration of advanced carriers, optical fibers, and microfluidics opens up new possibilities for innovative and targeted therapeutic approaches.
Introduction:Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.Methods:Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release.Results:PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.Conclusion:The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.
In-fiber core-to-cladding coupling components for heating purposes have been well assessed in the last decades. Here we demonstrate the use of Turn-Around-Point Long Period Grating as coupling mechanism for highly efficient heating devices fabrication.
The use of in-fiber core-to-cladding coupling components for thermal heating purposes has been well assessed in the last decades within the development of fiber optic devices for flow measurements and water thermal conductivity calculation. In these devices, light travelling in the fiber core is transferred into the cladding and absorbed by a metallic layer surrounding the fiber, with the consequent resistive heating generation. Here we demonstrate the use of a Turn-Around-Point (TAP) Long Period Grating (LPG) as resonant core-to-cladding light coupling mechanism for the fabrication of a highly efficient heating device based on metallic coated Fiber Bragg Grating (FBG). A properly designed TAP LPG was fabricated by means of point-to-point UV laser and spliced to a 150 nm thick Au-coated FBG. The heating efficiency characterization of the final device was analyzed, in both air and water, by evaluating the temperature increase in the gold layer surrounding the FBG at incremental values of the injected power. Collected results confirm that the use of LPGs involving the excitation of higher order cladding modes provides an excellent transferring mechanism of the fiber core light into the cladding, which in turn guarantees very high thermal heating efficiency to the final device. Moreover, by comparing such results with the performance of other in-fiber core-to-cladding coupling components already presented in literature, it was found that the TAP LPG-based device exhibits an actuation efficiency 2.5 times greater, thus resulting the most effective and highly performing solution for energy transfer to the metallic overcoat.
Lab-on-fiber (LOF) optrodes are recently emerging not only as valid platforms for biosensing, but also as promising light-controlled actuators in drug-delivery, optical trapping and thermo-ablation systems. In this regard, the thermo-plasmonic effect has been recognized as an intriguing tool for conferring to the optical fiber the capability of interacting with the external environment through the fine control of local overheating actuated by light in the range of few mW. However, the evaluation of the thermo-plasmonic overheating on small areas such as that of a standard single mode fiber tip is not trivial, especially in liquid solutions, where these probes typically operate. Here we demonstrate that by functionalizing the metallic nanostructure of LOF devices with a thermoresponsive smart materials, it is possible to measure the light-induced overheating on the fiber tip. Specifically, we monitored the plasmonic resonance wavelength shift induced by the temperature-dependent swelling dynamics of different microgel films deposited on the nanostructure. We find a local overheating of about 8 °C mW−1, i.e. also in line with our theoretical predictions based on numerical simulations. Our results demonstrate that the proposed approach is a valid methodology for the direct and continuous monitoring of the temperature changes in LOF devices induced by the input optical power in liquid environment. Our findings lay the basis for the analysis of thermo-plasmonic optical fiber probes exploitable in many applications, especially for the life science sector.
The thermoplasmonic effect causing the local overheating in nanostructured metallic substrates has been re-cently recognized as an intriguing technological tool for the development of light-controlled active micro and nano systems. Here, we present a study of thermoplasmonic effect in Lab-on-Fiber devices, consisting in na-nostructured gold layers directly integrated onto the cleaved facet of an optical fiber tip. We analyze the effect of the metallic nanostructure parameters on the temperature distribution under different (in-fiber) illumination conditions. Heating and cooling temporal dynamics are also investigated. At the steady state, a linear re-lationship between input optical power and temperature with a linear coefficient in the order of 10 degrees C/mW is found. All the experimental results are in good agreement with numerical simulations based on a finite element method. Our findings lay the groundwork for the development of light triggered active Lab-on-Fiber probes, merging the unique characteristics of the optical fiber platform and the enormous potentiality offered by thermoplasmonics.
We present a very simple and versatile fiber optic sensor for liquid level measurements based on the Archimedes' law of buoyancy. It includes a proper mass suspended in the liquid with one end fixed to a fiber Bragg grating (FBG) strain sensor, while the remaining fiber termination is fixed to a rigid support. When the liquid level increases inside the tank, the load exerted by the suspended mass on the optical fiber is reduced as a consequence of the increase of the force acting on the immersed mass according to the Archimedes' law of buoyancy, leading to a reduction of the strain applied to the FBG. The proposed device is able to perform real time and continuous liquid level measurements, and is characterized by sensing features (such as sensitivity and operating range) that exclusively depend on the geometrical characteristics (e.g., shape, diameter, and length) of the suspended mass. Therefore, by a judicious selection of its geometrical features, the proposed device can be customized so as to suit the requirements for the specific application. In addition, the constitutive material of the attached mass can be properly selected in order to confer to the proposed platform the capability to operate in any kind of liquid. Here, as proof of principle, we exploited an aluminium cylindrical mass having a radius of 8 mm and a length of 30 cm, and experimentally demonstrated the capability of the realized device to measure the water level inside a beaker over a range of 25 cm with a sensitivity of similar to 27 pm/cm, a resolution of similar to 0.04 cm, and a repeatability error of similar to 0.1% of the full scale reading. We also demonstrated, both theoretically and experimentally, the possibility to largely tune the sensing performances by acting on the cylinder radius. Obtained results pave the way for the exploitation of the proposed platform for accurate liquid level monitoring in large-scale storage tanks, useful both for petrochemical industry and for agricultural/residential applications.
We present a very simple and versatile fiber optic sensing platform for real time and continuous liquid level measurement. It includes a proper mass suspended in the liquid with one end fixed to a Fiber Bragg Grating (FBG) strain sensor, while the other fiber termination is fixed to a rigid support. When the liquid level increases inside the tank, the load exerted by the suspended mass on the optical fiber is reduced as a consequence of the increase of the buoyant force acting on the immersed mass, thus leading to a reduction of the strain applied to the FBG. Here, just as proof of principle, we exploited an aluminum cylindrical mass having a radius of 8mm, and experimentally demonstrated the capability of the realized platform to measure the water level inside a beaker over a range of 25 cm with a sensitivity of ~27pm/cm and a resolution of ~0.1% of the full scale reading (FSR).
This work deals with the fabrication, prototyping, and experimental validation of a fiber optic thermo-hygrometer-based soil moisture sensor, useful for rainfall-induced landslide prevention applications. In particular, we recently proposed a new generation of fiber Bragg grating (FBGs)-based soil moisture sensors for irrigation purposes. This device was realized by integrating, inside a customized aluminum protection package, a FBG thermo-hygrometer with a polymer micro-porous membrane. Here, we first verify the limitations, in terms of the volumetric water content (VWC) measuring range, of this first version of the soil moisture sensor for its exploitation in landslide prevention applications. Successively, we present the development, prototyping, and experimental validation of a novel, optimized version of a soil VWC sensor, still based on a FBG thermo-hygrometer, but able to reliably monitor, continuously and in real-time, VWC values up to 37% when buried in the soil.