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Chiral Polyproline Enables Functional Stealth for Simultaneous Long Circulation and Endoplasmic Reticulum-Targeted

Mingdi Hu1,2, Yahui He3, Liyuan Wu4

  • 1New Cornerstone Science Laboratory, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

ACS Nano
|February 21, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces functional stealth polymers using chiral polyproline (PP) to improve nanomedicine circulation and targeting. L-type polyproline (PLP) modified nanoparticles evade immune clearance and enhance nanovaccine efficacy by targeting the endoplasmic reticulum (ER).

Keywords:
chiral nanovaccinechiral polyprolineendoplasmic reticulum targetingfunctional stealthprotein corona

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Immunology

Background:

  • Traditional stealth polymers for nanomedicine offer passive antifouling but lack functionality.
  • This limits their ability to actively control nanoparticle behavior in vivo.

Purpose of the Study:

  • To develop a "functional stealth" strategy using chiral polyproline (PP) to enhance nanomedicine circulation and intracellular targeting.
  • To engineer gold nanoparticles (AuNPs) with l-polyproline (PLP) for improved stealth and endoplasmic reticulum (ER) targeting.

Main Methods:

  • Engineered AuNPs modified with l-polyproline (PLP) and d-polyproline (PDP).
  • Investigated nanoparticle interaction with blood components and macrophage clearance.
  • Assessed ER targeting capability via HSP47 chaperone interaction.
  • Developed chiral nanovaccines by loading tumor antigen peptides onto PLP-AuNPs.

Main Results:

  • L-type AuNPs exhibited superior stealth performance by recruiting dysopsonins and inhibiting opsonin adsorption, evading rapid clearance.
  • PLP-modified nanoparticles selectively targeted the ER by interacting with HSP47.
  • Chiral nanovaccines demonstrated enhanced antigen presentation via ER accumulation and improved MHC I pathway entry.
  • PLP-AuNPs significantly suppressed tumor growth by eliciting potent antigen-specific cellular immunity.

Conclusions:

  • Surface chiral topology can program nanoparticle fate and immune function.
  • Polyproline (PP) represents a "functional stealth" polymer capable of evading clearance and activating targeted intracellular functions.
  • This approach offers a new paradigm for designing advanced nanomedicines and nanovaccines.