pH‐Responsive Motors and their Interaction with RAW 264.7 Macrophages

Abstract

sues. Exploring the benefit of motors over their passively diffusing counterparts in cell culture or in animal models attracted substantial attention in the past years. [5,6] Early examples focused on externallydriven motors that made use of physical stimuli to propel in low-density media. Recent examples include the use of nearinfrared (NIR) light-activated motors to penetrate a 3D cell tumor culture, which selectively induced cell apoptosis upon NIR irradiation or resulted in depleted amyloid aggregation. [7] Similarly, magnetically driven motors made of CaCO 3 and Fe 3 O 4 showed an increased cellular uptake since their mobility allowed for more efficient approaching of the target area. [8] The decomposition of the core particle in the acidic environment of the lysosomes assisted cargo release. In a different approach, Shen et al. employed Zn-doped iron oxide rods that swarmed and eventually spun under a rotating magnetic field, inducing cell death. [9] This effect was also assessed in vivo, where the size of tumors generated in mice decreased 4× upon magnetic therapy. Further, ultrasound-powered motors used for antigen delivery showed a 5-7-fold increase in cell penetration compared to passive particles. [10] Alternatively, motors that harvest energy from their local environment are a powerful option to design truly autonomous motors. There are examples of motors that showed locomotion in simple 2D cell models as well as more complex 3D cultures and even in animal models. Mesoporous silica particles [11] or liposomes [12,13] were chosen to assess cellular uptake in 2D cultures, showing promising results. For instance, Llopis-Lorente et al. engineered a mesoporous silica motor that moved due to the conversion of urea into ammonia and CO 2 . [14] After entrapment in the lysosomes, a 4× lower motor concentration was needed to release the same amount of cargo as their passive particle counterparts, an aspect that was attributed to the enhanced diffusion of the motors. Further, Wilson and co-workers designed a drug-loaded liposome-based motor that gained locomotion in the acidic pH generated in the surroundings of HeLa cells. [15] These motors showed a chemo tactic behavior towards acidic environments where they reached speeds up to ≈9 µm s −1 at pH 4.6.Other motors were able to penetrate 3D cell environments or tissues. For example, we showed that collagenase-propelled motors posed velocities up to 22 µm s −1 in collagen fiber networks, being eventually able to enhance penetration into bone Nano/micromotors are self-propelled particles that use external stimuli to gain locomotion outperforming Brownian motion. Here, three different polymers are employed that are conjugated to silica particles through a pH-labile linker. At slightly acidic pH, the linkers hydrolyze and release the polymeric chains, resulting in enhanced locomotion. The motors show a maximum velocity of ≈3 µm s −1 in cell media when poly(ethylene glycol) methyl ether methacrylate is asymmetrically distributed on the surface of the particles. Furthe...

Self‐Immolative Polymers to Initiate Locomotion in Motors

“…The current design allowed for a top average velocity of ~3 μm s À 1 . This velocity was comparable to other motors driven by disintegrating Polymer layers disassembly at basic pH (A), [7] polymer brushes disassembly at acidic pH (B), [9] the current effort (C), and surface polymerization (D). [8] polymer coatings (Figure 4, A-C).…”

“…In addition, we illustrated that Janus (asymmetrically coated) motors, which were equipped with a pH-responsive polymer coating, exhibited velocities up to 3 μm s À 1 when then the polymer chains detached due to the cleavage of the acidlabile linker. [9] Here, we aimed to explore the use of self-immolative polymers (SIP) to induce self-propelled locomotion in particles. Specifically, we i) synthesized SIP1 and SIP2 consisting of a poly(benzylcarbamate) backbone with a cap that could be triggered with BSA (bovine serum albumin) and hydrogen peroxide, respectively, ii) confirmed the disassembly of SIP1 in solution, iii) illustrated the SIP1/2 conjugation to silica particles to obtain motors, and iv) characterized their locomotion properties (Scheme 1).…”

On Nanomachines and Their Future Perspectives in Biomedicine

“…The linker was cleaved and the polymer brushes were released when exposed to acid pH or cell media, increasing the motor locomotion. [ 121 ] The motors displayed velocities up to ≈3 µm s −1 in cell media when Janus (asymmetric) motors were used with the uptake of the motors by RAW 264.7 macrophages increased up to 5 × compared to motors without the pH‐responsive linker, probably due to the enhanced diffusion of the motors.…”

“…However, when complex or less common locomotion properties are observed, more elaborate tools are needed to assess the locomotion, for instance when motors underwent deceleration. [ 121 ]…”

“…However, when complex or less common locomotion properties are observed, more elaborate tools are needed to assess the locomotion, for instance when motors underwent deceleration. [121] Theoretical predictions have also facilitated the understanding of the self-diffusiophoretic principle of Janus motors. For example, Lauga and Spagnolie [1,141] and Gaspard and Kapral [142] described and advanced several aspects of the selfdiffusiophoretic mechanisms for Janus motors.…”