Ultrafast light-activated polymeric nanomotors

Micro/nanomotors can convert energy into mechanical motion and offer promise for biomedical delivery, sensing, and therapy. Compared to passive nanocarriers, active particles can better engage with cells and even cross membranes. Prior light-driven, bubble-driven, and enzyme/bi-metallic systems demonstrate diverse propulsion mechanisms powered by chemical fuels or external fields (magnetic, ultrasound, light). Thermophoretic, light-powered systems have achieved among the highest reported velocities (up to ~86 µm s−1), offering fine spatiotemporal control. However, building fast, biodegradable polymeric nanomotors remains challenging due to difficulties in spatially controlling deposition of the active component (e.g., gold) and leveraging sub-10-nm plasmonic features on soft polymeric chassis. The study aims to design and understand an ultrafast, biodegradable, light-activated nanomotor and to demonstrate its applicability for intracellular cargo delivery.

• Light-propelled nanomotors and thermophoretic propulsion offer high control and among the highest speeds reported (~86 µm s−1) using plasmonic heating.
• Au-based nanomotors have used various morphologies (spheres, shells, rods, stars) via covalent conjugation or sputter coating, but spatially controlled deposition on soft nanomotor chassis is difficult.
• Most Au structures used exceed 10 nm; smaller Au NPs could improve energy conversion efficiency and enable more controlled deposition, benefiting nanomedical applications.
• Biodegradable polymeric stomatocytes (PEG-PDLLA) provide inherent asymmetry for directional motion and have been previously used as chassis, but achieving ultrafast, robust motion with controlled Au NP distribution remained an open challenge.

• Materials and chassis preparation: Three PEG-PDLLA block copolymers (PEG22-PDLLA95, PEG44-PDLLA95, NH2-PEG67-PDLLA95) were synthesized by ring-opening polymerization and characterized by 1H NMR and GPC. Copolymers (5:4:1 w/w) were self-assembled via solvent switch (THF/dioxane to water) to form polymersomes, followed by osmotic-induced shape transformation (dialysis against 50 mM NaCl) to generate bowl-shaped stomatocytes.
• Au NP functionalization: ~5 nm Au nanoparticles were grown in situ on the outer surface by mixing stomatocytes (3.33 mg mL−1) with PAA and HAuCl4, followed by NaBH4 reduction. Deposition relied on electrostatic and hydrogen-bond interactions. Au-coated spherical polymersomes were prepared similarly as controls.
• Characterization: DLS for hydrodynamic size/PDI; zeta potential; UV–vis extinction spectra; cryo-TEM for morphology and Au coverage; cryo-ET for 3D spatial distribution and quantitative analysis of Au NP number/density (outer surface, neck, cavity) with angular and axial density mapping.
• Photothermal measurements: Aqueous samples irradiated with 660 nm laser (0.75–1.5 W) for up to 10 min; temperature rise (ΔT) measured vs concentration and power; cyclic heating–cooling stability tested; IR thermography; post-irradiation structural integrity assessed by cryo-TEM.
• Motion analysis: Nanoparticle tracking analysis under 660 nm irradiation; MSD and velocities derived using Golestanian's model. Controls included pure stomatocytes, Au-polymersomes, and 300 nm Au NPs. Directionality was modulated by changing laser incidence; cyclic on–off tests assessed robustness; media effects tested in water, PBS, and DMEM.
• Simulations: FEM using cryo-ET-derived Au density maps to compute temperature fields and gradients (VT) around moving stomatocytes at different powers; drag force calculations vs speed; relation between VT, input power, and propulsion force Fa.
• Biocompatibility and delivery: CCK-8 viability in HeLa, 4T1, NIH/3T3. DOX loading to visualize motion and uptake. Two-photon CLSM under 800 nm irradiation to monitor interactions with HeLa. Active delivery assays for Cy5-siRNA and FITC-BSA under NIR; control groups with pure stomatocytes. Penetration studies with DOX-loaded Au-stomatocytes in 2D HeLa cultures and 3D HeLa spheroids under varied laser powers; confocal imaging and Z-stacks.

• Efficient photothermal conversion: Under 660 nm, 1.5 W for 10 min, Au-stomatocytes (3.33 mg mL−1) reached ΔT = 27.2 K, vs pure stomatocytes ΔT = 10.5 K and water ΔT = 6.8 K; heating scaled with concentration and power and was stable over ≥5 on–off cycles.
• Ultrafast, controllable motion: Directional autonomous motion opposite to the laser source (negative phototaxis) with speeds up to 124.7 ± 6.6 µm s−1 at 1.5 W in water; robust over 5 irradiation cycles; speed tunable by laser power and maintained in biological media (PBS: 109 ± 3.3 µm s−1; DMEM: 104 ± 3.7 µm s−1). Controls (Au-polymersomes, pure stomatocytes, 300 nm Au NPs) showed only enhanced Brownian motion.
• Au NP characteristics and distribution: Au NP diameter 4.5 ± 1.2 nm (n≈500). Cryo-ET revealed full outer-surface coverage with sparse Au in the neck and cavity (~6000 NPs outside, ~30 in neck, ~20 inside cavity for a representative particle). Radially homogeneous distribution in X–Y, but axial (Z) asymmetry with higher Au density at the bottom than near the opening, establishing a well-defined axial temperature gradient upon irradiation.
• Thermophoretic propulsion mechanism: FEM simulations using ET-derived maps showed an average axial temperature gradient VT ≈ −100 µK µm−1 at 1.5 W. Calculated propulsion to overcome drag at 125 µm s−1 requires ~−0.3 pN. Fa scaled linearly with VT (Fa = C·VT), supporting thermophoresis as the primary propulsion mechanism.
• Biocompatibility and active delivery: High cell viability (≈90%) across HeLa, 4T1, NIH/3T3; under 660/808 nm, 1 W, 5 min, viability remained ≥~80%. Rapid, light-assisted delivery of Cy5-siRNA and FITC-BSA into HeLa cells, with siRNA detectable intracellularly within ~6 s when using Au-stomatocytes; no uptake in controls. DOX-loaded motors showed enhanced accumulation and penetration in 2D HeLa cultures and 3D spheroids with increasing laser power (0, 1, 1.5 W).

The study addresses the challenge of creating fast, biodegradable polymeric nanomotors by leveraging densely packed sub-5-nm Au nanoparticles on asymmetric PEG-PDLLA stomatocytes. Detailed cryo-ET quantification revealed a crucial axial asymmetry in Au NP surface density that produces a strong temperature gradient under NIR irradiation. This gradient drives thermophoretic propulsion, explaining the ultrafast velocities exceeding prior reports for similar systems and the observed negative phototaxis. The motors retained high speeds in PBS and DMEM, indicating robustness for biomedical contexts. Comparative controls (Au-coated spherical polymersomes, pure stomatocytes, isolated Au NPs) confirm that both the stomatocyte geometry and the specific Au NP spatial distribution are essential for propulsion. The demonstrated rapid, light-triggered delivery of otherwise cell-impermeable cargos (siRNA, protein) and enhanced penetration in 3D spheroids underscore the relevance for intracellular delivery and tumor targeting.

The authors engineered biodegradable, light-propelled stomatocyte nanomotors by uniformly coating the outer surface with densely packed ~5 nm Au NPs via electrostatic and hydrogen-bond interactions. Upon NIR irradiation, these Au-stomatocytes achieved ultrafast, controllable motion (up to ~125 µm s−1) with excellent photothermal stability. Quantitative cryo-ET uncovered an axial asymmetry in Au NP distribution that creates a temperature gradient, yielding sub-picoNewton thermophoretic forces sufficient for propulsion. The motors enabled rapid intracellular delivery of diverse cargos and improved penetration in 3D tumor models, highlighting their potential for nanomedicine. This work provides a robust strategy for high-performance, biodegradable soft nanomotors with strong application prospects in biomedicine.