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Multistage signal-interactive nanoparticles improve tumor targeting through efficient nanoparticle-cell

Feng Zhang1, Yiran Zhang2, Li Kong3

  • 1Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki 00014, Finland; Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, P.R. China.

Cell Reports
|May 26, 2021
PubMed
Summary

Researchers developed novel signal-interactive nanoparticles (NPs) that improve communication with cells. These "smart" NPs enhance tumor targeting and suppression while reducing liver accumulation and injury.

Keywords:
multistage signal interactionnanoparticle-cell communicationreversible self-mimickingtumor targeting

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery

Background:

  • Biological component communication is vital for homeostasis.
  • Therapeutic nanoparticles (NPs) often lack communication, leading to clearance and limited tumor accumulation.
  • Existing NPs struggle with cellular interaction, impacting therapeutic efficacy.

Purpose of the Study:

  • To engineer a multistage signal-interactive system for therapeutic nanoparticles.
  • To enhance NP communication with the cellular environment for improved homeostasis and therapeutic outcomes.
  • To overcome limitations of current NPs, including macrophage-mediated clearance and poor tumor targeting.

Main Methods:

  • Developed a signal-interactive system on porous silicon particles.
  • Integrated Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide for a hierarchical chimeric signaling interface.
  • Incorporated "don't eat me" and "eat me" signals for controlled cellular interaction.
  • Utilized amantadine for NP transformation and signal conversion via reversible self-mimicking.

Main Results:

  • Signal-interactive NPs demonstrated improved tumor targeting (2.8-fold increase).
  • Enhanced tumor suppression was observed (6.5-fold increase) compared to non-interactive controls.
  • Reduced liver accumulation (51%) and restricted hepatic injury were noted with the novel NPs.

Conclusions:

  • The developed biochemical transceiver system effectively enhances NP-cellular communication.
  • Signal-interactive NPs show significant potential for improved cancer therapy by optimizing drug delivery and minimizing side effects.
  • This approach offers a new strategy for designing autonomous therapeutic nanoparticles with enhanced targeting and reduced toxicity.