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.
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).
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.
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