Janus Micromotors for Photophoretic Motion and Photon Upconversion Applications Using a Single Near-Infrared Wavelength.

External stimuli can trigger changes in temperature, concentration, and momentum between micromotors and the medium, causing their propulsion and enabling them to perform different tasks with improved kinetic efficiencies. Light-activated micromotors are attractive systems that achieve improved motion and have the potential for high spatiotemporal control. Photophoretic swarming motion represents an attractive means to induce micromotor movement through the generation of temperature gradients in the medium, enabling the micromotors to move from cold to hot regions. The micromotors studied herein are assembled with Fe3O4 nanoparticles, and NaGdF4:Yb3+,Er3+/NaGdF4:Yb3+ and LiYF4:Yb3+,Tm3+ upconverting nanoparticles. The Fe3O4 nanoparticles were localized to one hemisphere to produce a Janus architecture that facilitates improved upconversion luminescence with the upconverting nanoparticles distributed throughout. Under 976 nm excitation, Fe3O4 nanoparticles generate the temperature gradient, while the upconverting nanoparticles produce visible light that is used for micromotor motion tracking and triggering of reactive oxygen species generation. As such, the motion and application of the micromotors are achieved using a single excitation wavelength. To demonstrate the practicality of this system, curcumin was adsorbed to the micromotor surface and degradation of Rhodamine B was achieved with kinetic rates that were over twice as fast as the static micromotors. The upconversion luminescence was also used to track the motion of the micromotors from a single image frame, providing a convenient means to understand the trajectory of these systems. Together, this system provides a versatile approach to achieving light-driven motion while taking advantage of the potential applications of upconversion luminescence such as tracking and detection, sensing, nanothermometry, particle velocimetry, photodynamic therapy, and pollutant degradation.

Cytotoxicity and Genotoxicity of Azobenzene-Based Polymeric Nanocarriers for Phototriggered Drug Release and Biomedical Applications.

Drug nanoencapsulation increases the availability, pharmacokinetics, and concentration efficiency for therapeutic regimes. Azobenzene light-responsive molecules experience a hydrophobicity change from a polar to an apolar tendency by trans-cis photoisomerization upon UV irradiation. Polymeric photoresponse nanoparticles (PPNPs) based on azobenzene compounds and biopolymers such as chitosan derivatives show prospects of photodelivering drugs into cells with accelerated kinetics, enhancing their therapeutic effect. PPNP biocompatibility studies detect the safe concentrations for their administration and reduce the chance of side effects, improving the effectiveness of a potential treatment. Here, we report on a PPNP biocompatibility evaluation of viability and the first genotoxicity study of azobenzene-based PPNPs. Cell line models from human ventricular cardiomyocytes (RL14), as well as mouse fibroblasts (NIH3T3) as proof of concept, were exposed to different concentrations of azobenzene-based PPNPs and their precursors to evaluate the consequences on mitochondrial metabolism (MTT assay), the number of viable cells (trypan blue exclusion test), and deoxyribonucleic acid (DNA) damage (comet assay). Lethal concentrations of 50 (LC50) of the PPNPs and their precursors were higher than the required drug release and synthesis concentrations. The PPNPs affected the cell membrane at concentrations higher than 2 mg/mL, and lower concentrations exhibited lesser damage to cellular genetic material. An azobenzene derivative functionalized with a biopolymer to assemble PPNPs demonstrated biocompatibility with the evaluated cell lines. The PPNPs encapsulated Nile red and dofetilide separately as model and antiarrhythmic drugs, respectively, and delivered upon UV irradiation, proving the phototriggered drug release concept. Biocompatible PPNPs are a promising technology for fast drug release with high cell interaction opening new opportunities for azobenzene biomedical applications.

Photosensitive Polymeric Janus Micromotor for Enzymatic Activity Protection and Enhanced Substrate Degradation.

Immobilizing enzymes into microcarriers is a strategy to improve their long-term stability and reusability, hindered by (UV) light irradiation. However, in such approaches, enzyme-substrate interaction is mediated by diffusion, often at slow kinetics. In contrast, enzyme-linked self-propelled motors can accelerate this interaction, frequently mediated by the convection mechanism. This work reports on a new photosensitive polymeric Janus micromotor (JM) for UV-light protection of enzymatic activity and efficient degradation of substrates accelerated by the JMs. The JMs were assembled with UV-photosensitive modified chitosan, co-encapsulating fluorescent-labeled proteins and enzymes as models and magnetite and platinum nanoparticles for magnetic and catalytic motion. The JMs absorbed UV light, protecting the enzymatic activity and accelerating the enzyme-substrate degradation by magnetic/catalytic motion. Immobilizing proteins in photosensitive JMs is a promising strategy to improve the enzyme's stability and hasten the kinetics of substrate degradation, thereby enhancing the enzymatic process's efficiency.

Polymeric Micro/Nanocarriers and Motors for Cargo Transport and Phototriggered Delivery.

Smart polymer-based micro/nanoassemblies have emerged as a promising alternative for transporting and delivering a myriad of cargo. Cargo encapsulation into (or linked to) polymeric micro/nanocarrier (PC) strategies may help to conserve cargo activity and functionality when interacting with its surroundings in its journey to the target. PCs for cargo phototriggering allow for excellent spatiotemporal control via irradiation as an external stimulus, thus regulating the delivery kinetics of cargo and potentially increasing its therapeutic effect. Micromotors based on PCs offer an accelerated cargo-medium interaction for biomedical, environmental, and many other applications. This review collects the recent achievements in PC development based on nanomicelles, nanospheres, and nanopolymersomes, among others, with enhanced properties to increase cargo protection and cargo release efficiency triggered by ultraviolet (UV) and near-infrared (NIR) irradiation, including light-stimulated polymeric micromotors for propulsion, cargo transport, biosensing, and photo-thermal therapy. We emphasize the challenges of positioning PCs as drug delivery systems, as well as the outstanding opportunities of light-stimulated polymeric micromotors for practical applications.

Photosensitive nanocarriers for specific delivery of cargo into cells.

Nanoencapsulation is a rapidly expanding technology to enclose cargo into inert material at the nanoscale size, which protects cargo from degradation, improves bioavailability and allows for controlled release. Encapsulation of drugs into functional nanocarriers enhances their specificity, targeting ability, efficiency, and effectiveness. Functionality may come from cell targeting biomolecules that direct nanocarriers to a specific cell or tissue. Delivery is usually mediated by diffusion and erosion mechanisms, but in some cases, this is not sufficient to reach the expected therapeutic effects. This work reports on the development of a new photoresponsive polymeric nanocarrier (PNc)-based nanobioconjugate (NBc) for specific photo-delivery of cargo into target cells. We readily synthesized the PNcs by modification of chitosan with ultraviolet (UV)-photosensitive azobenzene molecules, with Nile red and dofetilide as cargo models to prove the encapsulation/release concept. The PNcs were further functionalized with the cardiac targeting transmembrane peptide and efficiently internalized into cardiomyocytes, as a cell line model. Intracellular cargo-release was dramatically accelerated upon a very short UV-light irradiation time. Delivering cargo in a time-space controlled fashion by means of NBcs is a promising strategy to increase the intracellular cargo concentration, to decrease dose and cargo side effects, thereby improving the effectiveness of a therapeutic regime.

Azopolymer based nanoparticles for phototriggered drug delivery.

Controlled release by stimulus-responsive nanoparticles is oriented to increase the specificity of drug delivery, to improve the therapy effectiveness and minimizing side effects. This work presents the synthesis of photosensitive-polymeric nanoparticles as a potential system for localized drug delivery. First, the photoisomerizable amphiphilic-copolymer poly2-[4-phenylazophenoxy]ethyl acrylate-co-acrylic acid (PPAPE), was synthesized. Then, PPAPE was employed to prepare micellar nanoparticles by the nanoprecipitation method. Characterizations of the polymer were performed by proton nuclear magnetic resonance, X-ray photoelectron spectroscopy and FTIR spectroscopy. The morphology of the nanoparticles was analyzed by dynamic light scattering and transmission electron microscopy. Also, photostimulation response was confirmed by UV-VIS spectroscopy. Results indicate that the obtained photoresponsive nanoparticles have the size and photoisomerization necessary to perform the specific release of drugs.