# All‐PEG‐Like Block Copolymers Self‐Assemble into Stealth Nanocarriers for Drug Delivery

## TL;DR

Researchers created stealth drug delivery nanoparticles using a PEG-like polymer that avoids immune detection and improves drug effectiveness.

## Contribution

A fully POEGMA-based stealth nanoparticle platform with tunable thermal responsiveness and high drug encapsulation efficiency is introduced.

## Key findings

- POEGMA nanoparticles self-assemble above room temperature with a block length ratio of at least 0.25.
- POEGMA-encapsulated doxorubicin showed enhanced in vivo efficacy and evaded anti-PEG antibodies.
- The nanoparticles can encapsulate diverse hydrophobic drugs with high loading efficiency.

## Abstract

Poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) is a stealth polymer that does not exhibit polyethylene glycol (PEG) antigenicity. Herein, we engineered self‐assembling nanoparticles composed entirely of POEGMA by designing AB diblock copolymers with varying oligo(ethylene glycol) (EG) side chains. We found that a one‐unit difference between di‐ and tri‐ethylene glycol side chains is sufficient to induce amphiphilicity and enables temperature‐triggered self‐assembly above room temperature when the block length ratio is at least 0.25. To broaden the temperature stability window, we increased amphiphilicity by incorporating mono‐ethylene glycol into the hydrophobic block via random copolymerization, yielding nanoparticles stable between 20°C–40°C. These POEGMA nanoparticles effectively encapsulate diverse hydrophobic drugs with high loading efficiency. Notably, POEGMA‐encapsulated doxorubicin retained the drug's in vitro activity and exhibited enhanced in vivo efficacy compared to free doxorubicin due to improved pharmacokinetics. Furthermore, these nanoparticles demonstrated stealth behavior by evading recognition by anti‐PEG antibodies. This study introduces a versatile, fully POEGMA‐based platform for stealth drug delivery with tunable thermal responsiveness and high therapeutic potential.

Self‐assembling nanoparticles composed entirely of POEGMA are engineered by exploiting side‐chain–dependent amphiphilicity and tunable thermoresponsive behavior. These single‐material nanocarriers encapsulate diverse hydrophobic drugs with high efficiency, retain therapeutic activity, improve in vivo efficacy, and evade anti‐PEG antibodies. The work establishes a versatile stealth alternative for next‐generation drug delivery.