# From Nanoparticle Design to Clinical Translation in Cancer Therapy

**Authors:** Jordi Puiggalí

PMC · DOI: 10.3390/ijms27052253 · International Journal of Molecular Sciences · 2026-02-27

## TL;DR

This review explores how nanoparticles are being designed and used in cancer therapy to improve drug delivery and immune responses, with a focus on clinical translation.

## Contribution

The paper provides a comprehensive overview of nanoparticle platforms and strategies for cancer treatment, emphasizing their design and clinical translation.

## Key findings

- Nanoparticles can actively target tumors and respond to the tumor microenvironment.
- Nanoparticle-based immunotherapy, including mRNA delivery, is a promising approach.
- Translational challenges like safety and regulatory issues remain significant barriers.

## Abstract

Nanoparticle-based strategies have emerged as a versatile and powerful approach for cancer therapy, enabling the integration of material science, molecular biology, and immunology into multifunctional therapeutic platforms. Over the past decade, significant advances in nanoparticle design have expanded their potential beyond passive drug carriers toward systems capable of active targeting, microenvironment-responsive behavior, and immune modulation. This review provides a comprehensive and up-to-date overview of the major nanoparticle platforms developed for cancer treatment, including lipid-based, polymeric, inorganic, and bioinspired nanomaterials, with particular emphasis on their structure–property relationships and biological interactions. We discuss key targeting strategies, spanning passive, active, stimuli-responsive, and cellular or immune-mediated approaches, and analyze how nanoparticles can overcome biological barriers imposed by the tumor microenvironment, such as abnormal vasculature, dense extracellular matrix, hypoxia, and immunosuppression. Special attention is given to nanoparticle-enabled cancer immunotherapy, including vaccine delivery, mRNA–lipid nanoparticle systems, and combination strategies that integrate immunotherapy with conventional treatments. Finally, we critically examine safety, toxicity, and translational challenges that continue to limit the clinical impact of cancer nanomedicine, highlighting the importance of biologically informed design, manufacturing robustness, and regulatory considerations. By synthesizing current advances and identifying emerging trends, this review aims to provide a framework for the rational development of next-generation nanoparticle-based cancer therapies with improved clinical relevance.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Diseases:** toxicity (MESH:D064420), hypoxia (MESH:D000860), Cancer (MESH:D009369)
- **Chemicals:** lipid (MESH:D008055)

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12984760/full.md

## References

126 references — full list in the complete paper: https://tomesphere.com/paper/PMC12984760/full.md

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Source: https://tomesphere.com/paper/PMC12984760