Optomagnetic nanofluids for controlled brain hyperthermia: a critical study.

Optomagnetic nanofluids (OMNFs) are colloidal dispersions of nanoparticles (NPs) with combined magnetic and optical properties. They are especially appealing in biomedicine since they can be used as minimally invasive platforms for controlled hyperthermia treatment of otherwise difficultly accessible tumors such as intracranial ones. On the one hand, magnetic NPs act as heating mediators when subjected to alternating magnetic fields or light irradiation. On the other hand, suitably tailored luminescent NPs can provide a precise and remote thermal readout in real time. The combination of heating and thermometric properties allows, in principle, to precisely monitor the increase in the temperature of brain tumors up to the therapeutic level, without causing undesired collateral damage. In this work we demonstrate that this view is an oversimplification since it ignores the presence of relevant interactions between magnetic (γ-Fe2O3 nanoflowers) and luminescent nanoparticles (Ag2S NPs) that result in a detrimental alteration of their physicochemical properties. The magnitude of such interactions depends on the interparticle distance and on the surface properties of nanoparticles. Experiments performed in mouse brains (phantoms and ex vivo) revealed that OMNFs cannot induce relevant heating under alternating magnetic fields and fail to provide reliable temperature reading. In contrast, we demonstrate that the use of luminescent nanofluids (containing only Ag2S NPs acting as both photothermal agents and nanothermometers) stands out as a better alternative for thermally monitored hyperthermia treatment of brain tumors in small animal models.

Clickable Albumin Nanoparticles for Pretargeted Drug Delivery toward PD-L1 Overexpressing Tumors in Combination Immunotherapy.

We present a simple methodology to design a pretargeted drug delivery system, based on clickable anti-programmed death ligand 1 (anti-PD-L1) antibodies (Abs) and clickable bovine serum albumin (BSA) nanoparticles (NPs). Pretargeted drug delivery is based on the decoupling of a targeting moiety and a drug-delivering vector which can then react in vivo after separate injections. This may be key to achieve active targeting of drug-delivering NPs toward cancerous tissue. In pretargeted approaches, drug-delivering NPs were observed to accumulate in a higher amount in the targeted tissue due to shielding-related enhanced blood circulation and size-related enhanced tissue penetration. In this work, BSA NPs were produced using the solvent precipitation methodology that renders colloidally stable NPs, which were subsequently functionalized with a clickable moiety based on chlorosydnone (Cl-Syd). Those reactive groups are able to specifically react with dibenzocyclooctyne (DBCO) groups in a click-type fashion, reaching second-order reaction rate constants as high as 1.9 M-1·s-1, which makes this reaction highly suitable for in vivo applications. The presence of reactive Cl-Syd was demonstrated by reacting the functionalized NPs with a DBCO-modified sulfo-cyanine-5 dye. With this reaction, it was possible to infer the number of reactive moieties per NPs. Finally, and with the aim of demonstrating the suitability of this system to be used in pretargeted strategies, functionalized fluorescent NPs were used to label H358 cells with a clickable anti-PD-L1 Ab, applying the reaction between Cl-Syd and DBCO as corresponding clickable groups. The results of these experiments demonstrate the bio-orthogonality of the system to perform the reaction in vitro, in a period as short as 15 min.

Sensors and bioassays powered by upconverting materials.

In recent years, considerable efforts have been done to better understand the peculiar emission properties of upconverting materials due to their widespread applications in different and important technological fields such as upconversion-based photoactivated cancer therapies, photoactivated drug-delivery, magnetic resonance imaging contrast agents, bioimaging. However, one of the most promising applications of upconverting materials concerns the field of sensing, due to their unique emission properties. In fact, the minimal autofluorescence, blinking, photo-bleaching, and high photostability makes them an excellent alternative to organic dyes or quantum dots. This article reviews the state-of-the-art, design, and sensing strategies of upconversion-based sensing platforms, with special attention to upconverting nanoparticles, as well as how the incorporation of these materials into pre-existing diagnostic tests and bioassays have improved their capabilities for the detection of different kinds of analytes.

Synthesis, Characterization, and Application in HeLa Cells of an NIR Light Responsive Doxorubicin Delivery System Based on NaYF4:Yb,Tm@SiO2-PEG Nanoparticles.

Herein, we present a phototriggered drug delivery system based on light responsive nanoparticles, which is able to release doxorubicin upon NIR light illumination. The proposed system is based on upconversion fluorescence nanoparticles of ß-NaYF4:Yb,Tm@SiO2-PEG with a mean diameter of 52±2.5 nm that absorb the NIR light and emit UV light. The UV radiation causes the degradation of photodegradable ortho-nitrobenzyl alcohol derivates, which are attached on one side to the surface of the nanoparticles and on the other to doxorubicin. This degradation triggers the doxorubicin release. This drug delivery system has been tested "in vitro" with HeLa cells. The results of this study demonstrated that this system caused negligible cytotoxicity when they were not illuminated with NIR light. In contrast, under NIR light illumination, the HeLa cell viability was conspicuously reduced. These results demonstrated the suitability of the proposed system to control the release of doxorubicin via an external NIR light stimulus.