# Trojan Horse Strategy: How Biomimetic Nanomedicine Remodels the Tumor Microenvironment

## TL;DR

This review explores how biomimetic nanomedicine can reshape the tumor environment to improve cancer treatments by mimicking biological systems.

## Contribution

The paper systematically reviews the design, types, and mechanisms of biomimetic nanomedicines for tumor microenvironment remodeling.

## Key findings

- Biomimetic nanomedicines offer targeted delivery and reduced toxicity in tumor therapies.
- They enhance the effectiveness of immunotherapy by reprogramming immune cells in the tumor microenvironment.
- Challenges remain in clinical translation, including biosafety and scalable manufacturing.

## Abstract

Biomimetics is an interdisciplinary field that involves studying the structures, functions, principles, and behaviors of biological systems to draw inspiration and apply this knowledge to technological innovation and engineering design, thereby addressing complex challenges. ​​Biomimetic nanomedicine​​ represents a specific application of biomimetics within the realm of nanomedicine, where biological components are mimicked to construct sophisticated nanodrug delivery systems. These biomimetic nanosystems exhibit multiple unique advantages, including ​​targeted delivery to cells within the tumor microenvironment (TME)​​, ​​prolonged in vivo circulation time​​, ​​enhanced antigen/adjuvant loading capacity​​, and ​​high biocompatibility​​. These properties collectively ​​enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and photodynamic therapy (PDT)​​ by improving tumor‐specific targeting and reducing off‐target toxicity, thereby establishing biomimetic nanomedicines as ​​a promising platform for reprogramming the TME​​. This review highlights the ​​categorization​​, ​​design principles​​, and ​​manufacturing strategies​​ of biomimetic nanodrugs, providing a ​​systematic review​​ of the interplay between the TME and ​​biomimetic nanomedicines​​, and elucidating how their interaction potentiates tumor‐killing efficacy​​. Despite encouraging progress in biomimetic nanomedicines, challenges remain in their clinical translation, including biosafety concerns, scalable manufacturing processes, and optimal drug delivery efficiency. Advances in nanotechnology and precision engineering offer promising avenues for developing personalized biomimetic nanomedicines.

This review focuses on biomimetic nanomedicines for tumor microenvironment (TME) remodeling, covering their diverse biomimetic types, design principles, and mechanisms of immune cell reprogramming and reversal of immunosuppressive microenvironments, with particular emphasis on their application in synergistic immunotherapy. Given the current key clinical translation barriers for nanomedicines, new insights are proposed for future research directions.