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Transformable "Bullet Train"-like Nanomotors for Sequentially Overcoming Tumor Delivery Barriers
Yuan Liu1,2, Jie Meng1, Wenxiong Cao1
1Institute of Biomedical Engineering, College of Medicine, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, China.
Nano Letters
|December 18, 2025
Summary
This study introduces a novel transformable nanomotor designed to overcome chemotherapy delivery barriers. This "bullet train"-like nanomotor enhances tumor penetration and drug delivery for improved cancer treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery Systems
Background:
- Chemotherapeutics face significant delivery challenges, leading to low efficacy and adverse effects.
- Overcoming biological barriers in tumors is crucial for effective cancer treatment.
- Nanomaterials offer potential solutions for targeted drug delivery and improved therapeutic outcomes.
Purpose of the Study:
- To design and evaluate a "bullet train"-like transformable nanomotor, (f-JSN-u)n, for sequential tumor delivery barrier overcoming.
- To investigate the nanomotor's ability to enhance drug penetration, cellular uptake, and antitumor efficacy.
- To compare the performance of (f-JSN-u)3 nanomotor with its non-transformable counterpart (f-JSN-u).
Main Methods:
- Design of rod-shaped (f-JSN-u)n nanomotor assemblies inspired by bullet trains.
- Utilizing near-infrared (NIR) irradiation to trigger nanomotor transformation from rod-shaped to spherical.
- Employing folate-mediated endocytosis and glutathione-triggered drug release mechanisms within the tumor microenvironment.
- Evaluating nanomotor circulation time, tumor accumulation, penetration depth, cellular uptake, and antitumor efficacy in vivo.
Main Results:
- The rod-shaped (f-JSN-u)n nanomotors demonstrated long circulation and enhanced diffusion across tumor vasculature.
- NIR irradiation induced nanomotor dissociation into smaller spherical "carriages," facilitating deep tumor penetration and cellular uptake.
- (f-JSN-u)3 showed a 3.4-fold longer plasma half-life and over 3-fold higher tumor tissue distribution compared to f-JSN-u.
- Enhanced tumor penetration and significant antitumor efficacy were observed with the transformable nanomotor.
Conclusions:
- The "bullet train"-like transformable nanomotor (f-JSN-u)n effectively overcomes multiple tumor delivery barriers.
- The sequential transformation and motion strategies significantly improve nanomotor performance in vivo.
- This nanomotor design holds promise for enhancing chemotherapy efficacy and reducing side effects in cancer treatment.
