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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
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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.

Keywords:
Biological barriersDeep penetrationNanomotorRod-shaped nanoparticleStimuli-responsive transformability

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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.