# Recent progress of non-linear topological structure polymers: synthesis, and gene delivery

## TL;DR

This review discusses the synthesis and gene delivery applications of non-linear polymers, highlighting their advantages and challenges in nanomedicine.

## Contribution

The paper provides a comprehensive review of synthetic methods and performance of non-linear polymers for gene delivery.

## Key findings

- Non-linear polymers offer better gene delivery efficiency and targeting due to their complex structures.
- Synthetic methods like RAFT and click chemistry are effective but face challenges in complexity.
- Topological effects significantly enhance the transfection performance of polymeric vectors.

## Abstract

Currently, many types of non-linear topological structure polymers, such as brush-shaped, star, branched and dendritic structures, have captured much attention in the field of gene delivery and nanomedicine. Compared with linear polymers, non-linear topological structural polymers offer many advantages, including multiple terminal groups, broad and complicated spatial architecture and multi-functionality sites to enhance gene delivery efficiency and targeting capabilities. Nevertheless, the complexity of their synthesis process severely hampers the development and applications of nonlinear topological polymers. This review aims to highlight various synthetic approaches of non-linear topological architecture polymers, including reversible-deactivation radical polymerization (RDRP) including atom-transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, click chemistry reactions and Michael addition, and thoroughly discuss their advantages and disadvantages, as well as analyze their further application potential. Finally, we comprehensively discuss and summarize different non-linear topological structure polymers for genetic materials delivering performance both in vitro and in vivo, which indicated that topological effects and nonlinear topologies play a crucial role in enhancing the transfection performance of polymeric vectors. This review offered a promising guideline for the design and development of novel nonlinear polymers and facilitated the development of a new generation of polymer-based gene vectors.