Enzymatic Micromotors as a Mobile Photosensitizer Platform for Highly Efficient On‐Chip Targeted Antibacteria Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) functions when the light-excited photosensitizers transfer energy to oxygen molecules ( 3 O 2 ) to produce cytotoxic singlet oxygen ( 1 O 2 ) that can effectively kill cells or bacteria. However, the PDT efficacy is often reduced by the limited availability of 3 O 2 surrounding the photosensitizer and extremely short diffusion range of the photoactivated 1 O 2 . Herein, an enzymatic micromotor based on hollow mesoporous SiO 2 (mSiO 2 ) microspheres is constructed as a mobile and highly efficient photosensitizer platform. Carboxylated magnetic nanoparticles are connected with both hollow spheres and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin molecules through covalent linkage between amino and carboxylic groups within a one-step reaction. Due to the intrinsic asymmetry of the mSiO 2 spheres, the micromotors can be propelled by ionic diffusiophoresis induced by the enzymatic decomposition of urea. Via numerical simulation, the self-propulsion mechanism is clarified and the movement direction is identified. By virtue of active self-propulsion, the current system can overcome the long-standing shortcomings of PDT and significantly enhance the PDT efficacy by improving the accessibility of the photosensitizer to 3 O 2 and enlarging the diffusing range of 1 O 2 . Therefore, by proposing a new solution to the bottleneck problems of PDT, this work provides insightful perspectives to the biomedical application of multifunctional micro/nanomotors. applications, including targeted drug delivery, mini-surgery, biochemical sensing, and diagnostics. [13][14][15] In particular, MNMs as active carriers with the capability of cargo loading and controllable motion have great potentials for effective delivery of different types of cargos. [15] So far, researchers have also explored stimuli-responsive materials, [16][17][18][19] biomimetic materials, [20][21][22] and micro-organisms functionalized with nanomaterials [23] as MNMs to precisely transport cargos of drugs, [16,20,23,24] proteins, [18,22,25] and genes [19] in vitro and/or in vivo. Compared with traditional passive delivery, MNMs can perform tasks such as controlled navigation, rapid transportation, and active delivery of payloads to disease sites, and thus have paved way for on demand biomedical cargo transportation. [15] Inspired by these achievements, we envision that self-propelled MNMs can serve as a mobile photosensitizer platform to improve the availability of 3 O 2 as well as the diffusion range of 1 O 2 , which can consequently achieve highly efficient PDT process.

In vivo activation of pH-responsive oxidase-like graphitic-nanozymes for selective killing of Helicobacter pylori

“…With unique enzyme-like properties, we then investigated the antibacterial application of PtCo@G nanozymes in vitro. The effective target H. pylori capability of PtCo@G could signi cantly enhance antibacterial e cacy by increasing the concentration of ROS around the bacterial surface and reduce the damage to normal tissues 36,37 . Boronic acid is a bacteria-binding molecule, which can reversibly bind peptidoglycan from the surface of the bacterial cell wall, leading to the speci c capture of H. pylori [38][39][40] .…”

Leukocyte Membrane-Coated Liquid Metal Nanoswimmers for Actively Targeted Delivery and Synergistic Chemophotothermal Therapy

“…In particular, synthetic nanoswimmers may perform diverse operations in the biomedical field, including biosensing [ 13 , 14 ], diagnostics [ 15 , 16 ], precision surgery [ 17 ], laser tissue welding [ 18 ], and direct drug delivery [ 19 , 20 ]. In recent years, various strategies have been employed to propel such micro/nanoswimmers, including chemical reaction [ 21 , 22 ], light stimuli [ 23 – 25 ], and electric [ 26 , 27 ], magnetism [ 28 , 29 ], and acoustic [ 30 , 31 ] actuation. However, most of the nanoswimmers still rely on inorganic materials, such as SiO 2 , mesoporous silicon, and Fe 3 O 4 ; these formulations often fail to be useable in the biosystem for the systemic toxicity or poor biodegradability.…”

Biofilm Microenvironment-Responsive Nanotheranostics for Dual-Mode Imaging and Hypoxia-Relief-Enhanced Photodynamic Therapy of Bacterial Infections

“…and has been used for the treatment of cancer and bacterial infection [28,34,35]. Since it is difficult for bacteria to develop resistance to 1 O 2 , aPDT is regarded as an effective approach for the drug-resistant bacterial infection [32,36]. However, the therapeutic efficacy of aPDT would be restricted by hypoxia condition in biofilm-infected tissues [4,26] Figure S1, Supporting Information).…”