Light-driven nanomotors improve multimodal breast cancer treatment efficacy

The nanomotor starts with bowl‑shaped mesoporous polydopamine (PDA) nanoparticles. These biocompatible bowls are loaded with two key payloads: Fe(II) ions as a Fenton catalyst, and BNN6, a thermally sensitive NO donor. The resulting PFB nanoparticles are then cloaked with a fragment of MCF‑7 breast cancer cell membrane.

"This membrane camouflage does two things," says Professor Hu. "It helps the nanomotor evade immune clearance, and it provides homologous targeting-the membrane proteins recognize and bind specifically to the same type of cancer cells."

When exposed to an 808‑nm NIR laser, PFB@CM exhibits a strong photothermal effect. A 100‑ppm suspension heats up by 21.7 °C in 10 minutes, reaching around 49 °C. This localized heat not only kills cancer cells directly but also drives self‑thermophoretic propulsion. As the laser power increases from 0.5 to 1.5 W/cm², the nanomotor's speed rises from 3.2 to 8.7 μm/s, converting random Brownian motion into directed movement that enhances cellular uptake.

The photothermal effect triggers three simultaneous processes. First, heat accelerates the release of Fe(II) ions from the PDA matrix. In the acidic tumor microenvironment, these Fe(II) ions catalyze endogenous hydrogen peroxide via a Fenton‑like reaction, generating highly toxic hydroxyl radicals (·OH)-the basis of chemodynamic therapy. Second, the same heat decomposes BNN6, releasing NO in a precisely controlled, on‑demand fashion. "NO alone is potent, but its short half‑life and narrow therapeutic window require spatiotemporal precision," notes Professor Hu. "Here, NO is released only inside the tumor and only when the laser is on." Third, the ·OH and NO react to form peroxynitrite (ONOO⁻), a reactive nitrogen species even more cytotoxic than either parent molecule.

Experiments confirmed each step. Extracellular assays showed that PFB efficiently oxidizes TMB (colour change to blue) in the presence of H₂O₂, confirming ·OH generation. NO release, measured by Griess assay, reached 8.8 μM after laser irradiation and stopped when the laser was turned off, demonstrating excellent controllability. Using a peroxynitrite‑specific fluorescent probe, the team observed strong fluorescence only when PFB was combined with both H₂O₂ and NIR-clear evidence of ONOO⁻ formation.

In MCF‑7 breast cancer cells, PFB@CM alone achieved 36.8% growth inhibition at 100 ppm. Adding NIR laser irradiation raised inhibition to 87.2%, as shown by live/dead staining and CCK‑8 assays. The homologous targeting was validated by loading the nanomotors with doxorubicin: MCF‑7 cells took up significantly more drug than control HUVEC cells, and NIR irradiation further boosted uptake through active propulsion.

Moving to MCF‑7 tumor‑bearing nude mice, the team divided animals into six groups. The PFB@CM + NIR group received two 10‑min laser sessions at 6 and 24 hours after intravenous injection. Thermal imaging showed tumor temperatures rising to 50.7 °C, sufficient for both direct ablation and NO release. After 14 days, the PFB@CM + NIR group had a final tumor volume of only 20.6 mm³ and tumor weight of 11.4 mg-reductions of 98.0% and 97.6% compared to controls. Histological analysis (H&E, TUNEL, and Ki‑67 staining) confirmed extensive apoptosis and suppressed proliferation in the triple‑therapy group. Importantly, no significant body weight loss or organ damage was observed in any treatment group. H&E staining of heart, liver, spleen, lungs, and kidneys revealed no structural abnormalities, confirming the excellent biocompatibility of PFB@CM.

Professor Hu acknowledges that the current 808‑nm laser penetration depth (1–2 cm) limits the platform to superficial tumors. "We are exploring NIR‑II windows and magnetothermal triggering to reach deeper lesions," he says. "Also, while the cascade chemistry works, we need to optimize the NO/ROS ratio to avoid the pro‑tumour effects that low NO concentrations can sometimes cause." Nevertheless, PFB@CM represents a major step forward: a light‑driven, membrane‑cloaked nanomotor that actively homes to tumours, penetrates barriers, and unleashes a coordinated photothermal–chemodynamic–gas therapy cascade. "This design philosophy-integrating active motility, homologous targeting, and multimodality in one nanoparticle-could be adapted for other cancers and other therapeutic agents," concludes Professor Hu.

Authors of the paper include Ming Yang, Jian Hu, Zerui Li, Hanhan Xie, Hongri Gu, and Chengzhi Hu.

Source:

Beijing Institute of Technology

Journal reference: