RESUMO
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.
RESUMO
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.
Assuntos
Quitosana/química , Enzimas Imobilizadas/química , Nanopartículas de Magnetita/química , Movimento (Física) , Armoracia/enzimologia , Compostos Azo/química , Compostos Azo/efeitos da radiação , Catalase/química , Quitosana/efeitos da radiação , Peroxidase do Rábano Silvestre/química , Peróxido de Hidrogênio/química , Lacase/química , Fenômenos Magnéticos , Nanopartículas de Magnetita/efeitos da radiação , Platina/química , Platina/efeitos da radiação , Raios UltravioletaRESUMO
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.
RESUMO
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.