The nanomotor starts with bowl\u2011shaped 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\u20117 breast cancer cell membrane.<\/p>\n
“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.”<\/p>\n
When exposed to an 808\u2011nm NIR laser, PFB@CM exhibits a strong photothermal effect. A 100\u2011ppm suspension heats up by 21.7\u202f\u00b0C in 10\u202fminutes, reaching around 49\u202f\u00b0C. This localized heat not only kills cancer cells directly but also drives self\u2011thermophoretic propulsion. As the laser power increases from 0.5 to 1.5\u202fW\/cm\u00b2, the nanomotor’s speed rises from 3.2 to 8.7\u202f\u03bcm\/s, converting random Brownian motion into directed movement that enhances cellular uptake.<\/p>\n
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\u2011like reaction, generating highly toxic hydroxyl radicals (\u00b7OH)-the basis of chemodynamic therapy. Second, the same heat decomposes BNN6, releasing NO in a precisely controlled, on\u2011demand fashion. “NO alone is potent, but its short half\u2011life 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 \u00b7OH and NO react to form peroxynitrite (ONOO\u207b), a reactive nitrogen species even more cytotoxic than either parent molecule.<\/p>\n
Experiments confirmed each step. Extracellular assays showed that PFB efficiently oxidizes TMB (colour change to blue) in the presence of H\u2082O\u2082, confirming \u00b7OH generation. NO release, measured by Griess assay, reached 8.8\u202f\u03bcM after laser irradiation and stopped when the laser was turned off, demonstrating excellent controllability. Using a peroxynitrite\u2011specific fluorescent probe, the team observed strong fluorescence only when PFB was combined with both H\u2082O\u2082 and NIR-clear evidence of ONOO\u207b formation.<\/p>\n
In MCF\u20117 breast cancer cells, PFB@CM alone achieved 36.8% growth inhibition at 100\u202fppm. Adding NIR laser irradiation raised inhibition to 87.2%, as shown by live\/dead staining and CCK\u20118 assays. The homologous targeting was validated by loading the nanomotors with doxorubicin: MCF\u20117 cells took up significantly more drug than control HUVEC cells, and NIR irradiation further boosted uptake through active propulsion.<\/p>\n
Moving to MCF\u20117 tumor\u2011bearing nude mice, the team divided animals into six groups. The PFB@CM + NIR group received two 10\u2011min laser sessions at 6 and 24\u202fhours after intravenous injection. Thermal imaging showed tumor temperatures rising to 50.7\u202f\u00b0C, sufficient for both direct ablation and NO release. After 14\u202fdays, the PFB@CM + NIR group had a final tumor volume of only 20.6\u202fmm\u00b3 and tumor weight of 11.4\u202fmg-reductions of 98.0% and 97.6% compared to controls. Histological analysis (H&E, TUNEL, and Ki\u201167 staining) confirmed extensive apoptosis and suppressed proliferation in the triple\u2011therapy 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.<\/p>\n
Professor Hu acknowledges that the current 808\u2011nm laser penetration depth (1\u20132\u202fcm) limits the platform to superficial tumors. “We are exploring NIR\u2011II 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\u2011tumour effects that low NO concentrations can sometimes cause.” Nevertheless, PFB@CM represents a major step forward: a light\u2011driven, membrane\u2011cloaked nanomotor that actively homes to tumours, penetrates barriers, and unleashes a coordinated photothermal\u2013chemodynamic\u2013gas 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.<\/p>\n
Authors of the paper include Ming Yang, Jian Hu, Zerui Li, Hanhan Xie, Hongri Gu, and Chengzhi Hu.<\/p>\n
Source:<\/p>\n
Beijing Institute of Technology<\/a><\/p>\n Journal reference:<\/p>\n