A Universal Chemotactic Targeted Delivery Strategy for Inflammatory Diseases

Abstract

Above 50% of deaths can be attributed to chronic inflammatory diseases; thus, the construction of drug delivery systems based on effective interaction of inflammatory factors with chemotactic nanoparticles is meaningful. Herein, a zwitterion‐based artificial chemotactic nanomotor is proposed for universal precise targeting strategy in vivo, where the high level of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in inflammatory sites are used as a chemoattractant. Multidimensional static models, dynamic models, and in vivo models are established to evaluate chemotactic performance. The results show that the upregulated ROS and iNOS can induce the chemotaxis of nanomotors to diseased tissues in inflammation‐related disease models. Further, mesoscale hydrodynamics simulations are performed to explain the chemotactic behavior of the nanomotors. Such a chemotactic delivery strategy is expected to improve delivery efficiency and may be applicable to a variety of inflammatory diseases.

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

“…In order to solve the above problems, we report multifunctional near-infrared (NIR)-driven bowl-shaped polydopamine (PDA)-hemin-PEG-ferrocene (Fc) (PHPF) nanomotors (PHPF NMs) (Scheme ). The asymmetric bowl-shaped PDA can self-propel under NIR radiation, − which is conducive to the deep penetration of these therapeutic nanoagents into tumor. − Furthermore, polydopamine is highly adhesive due to its molecular structure with a high content of primary and secondary amines and catechol (3,4-dihydroxybenzene). These chemical groups also provide reactive sites for the functionalization of polydopamine, making it easy to bind a number of drugs.…”

Chemotactic NO/H2S Nanomotors Realizing Cardiac Targeting of G-CSF against Myocardial Ischemia-Reperfusion Injury

“…Accordingly, the NO/H 2 S nanomotors were designed and constructed using N -methacryl- l -arginine (M-Arg) and N -methacryloyl- l -cysteine (M-Cys) as monomers, respectively, and a polymeric shell layer wrapped around the outside of G-CSF by a radical polymerization reaction under reaction with a degradable cross-linking agent (Figure ). The M-Arg and M-Cys components of the shell layer react with ROS/iNOS and cystathionine gamma-lyase (CSE) present in the IRI microenvironment to produce nitric oxide (NO) and hydrogen sulfide (H 2 S), − respectively, forming the NO/H 2 S nanomotors. Subsequently, superoxide dismutase (SOD) is covalently cross-linked in the polymer shell layer to convert the surplus O 2 •– at the IRI site into H 2 O 2 , which can be further consumed by the nanomotors to yield NO, constituting a cascade effect that both converts ROS into nontoxic components and increases the motion efficiency of the nanomotors.…”

“…The nanomotors can use the specific affinity interaction (enzyme–substrate interaction) between the M-Arg in its component and the highly expressed iNOS in the IRI microenvironment to form a chemotactic effect to the IRI site, enabling effective targeting and retention in the IRI area . The nanomotors retained at the IRI site can effectively eliminate the high levels of ROS already present by exploiting the cascade effect between the SOD and M-Arg in their components.…”

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections

“…Artificial micro-/nanomotors capable of harvesting and converting surrounding energy into motive power have been the research interest of current studies. − Given their autonomous and controllable motion ability, these peculiar mobile platforms have been widely used in fields ranging from biomedical to environmental science, such as drug delivery, − minimally invasive surgery, , biosensing, , and environmental remediation. , Therefore, it is self-evident that diverse antimicrobial micromotors loaded with antibiotics, lysozymes, antimicrobial peptides, or metal components are devised to achieve active treatment of bacterial infections. ,,− Nevertheless, these man-made assembled robots inevitably face two major problems: limited loading capability and possible premature release of antibacterial payload once introduced into a complex biological environment, which would deleteriously affect their antibacterial efficacy. Indeed, NIR-II light-mediated photodynamic and photothermal therapies are promising for an in vivo antibacterial effect not only because of the preferred synergistic antimicrobial efficiency but also because of the advantages of NIR-II light (e.g., deep penetration, low optical absorption, minimal scattering from tissue, and maximum permissible exposure). − Hence, our pursued aptitudes are the development of NIR-II light-stimulated multifunctional nanomotors that are capable of photocatalytic and photothermal synergistic antimicrobial activities and that possess rapid motion properties, thus achieving controllable, safe, highly efficient, and thorough bacteria killing.…”

“…Currently, micro-/nanomotors have been developed with different propulsion mechanisms, including self-thermophoresis/diffusiophoresis, chemotactic effects, and bubble propulsion manner. ,− NIR-II light-mediated self-thermophoresis-driven motors are satisfactory in the treatment of bacterial infections because of their high spatial-temporal control, fast motion behavior, and deep-tissue photoactivation capability. , Two necessary criteria that have to be strictly met in constructing self-thermophoresis-driven antibacterial nanomotors are as follows: (1) Janus nanostructure to enable an asymmetric heat field gradient and consequent directional navigation and (2) enhanced photocatalytic activity and photothermal performance to impart a synergistic antibacterial effect. The most commonly studied plasmonic Au nanorods (NRs) and plasmonic semiconductor nanocrystals of nonstoichiometric copper chalcogenides (Cu 2–x E, E = S, Se, Te) support localized surface plasmon resonance (LSPR) in the NIR-II spectrum, resulting in strong optical absorption. − Owing to the plasmon coupling, which causes a remarkably improved electromagnetic field, many heteronanocrystals constituting Au NRs and copper chalcogenides are constructed and applied in the photocatalytic field .…”