Regulation of ferroptosis by nanotechnology for enhanced cancer immunotherapy

ABSTRACT

Introduction

This review explores the innovative intersection of ferroptosis, a form of iron-dependent cell death, with cancer immunotherapy. Traditional cancer treatments face limitations in efficacy and specificity. Ferroptosis as a new paradigm in cancer biology, targets metabolic peculiarities of cancer cells and may potentially overcome such limitations, enhancing immunotherapy.

Area Covered

This review centers on the regulation of ferroptosis by nanotechnology to augment immunotherapy. It explores how nanoparticle-modulated ferroptotic cancer cells impact the TME and immune responses. The dual role of nanoparticles in modulating immune response through ferroptosis are also discussed. Additionally, it investigates how nanoparticles can be integrated with various immunotherapeutic strategies, to optimize ferroptosis induction and cancer treatment efficacy. The literature search was conducted using PubMed and Google Scholar, covering articles published up to March 2024.

Expert Opinion

The manuscript underscores the promising yet intricate landscape of ferroptosis in immunotherapy. It emphasizes the need for a nuanced understanding of ferroptosis’ impact on immune cells and the TME to develop more effective cancer treatments, highlighting the potential of nanoparticles in enhancing the efficacy of ferroptosis and immunotherapy. It calls for deeper exploration into the molecular mechanisms and clinical potential of ferroptosis to fully harness its therapeutic benefits in immunotherapy.

KEYWORDS:

• Ferroptosis
• immunotherapy
• nanotechnology
• immune response
• immune checkpoint blockade
• vaccine

Article highlights

• This review explores the burgeoning field of ferroptosis regulation by nanotechnology in cancer immunotherapy, highlighting the potential of this approach to overcome limitations in traditional cancer treatments and enhance immunotherapeutic efficacy.

• The review underscores the importance of a comprehensive understanding of the molecular mechanisms underlying ferroptosis and its interplay with the immune system. This is crucial for the development of more effective nanotechnology-based strategies that can harness the full potential of ferroptosis in cancer immunotherapy.

• The integration of ferroptosis with immunotherapy strategies, such as immune checkpoint blockade and cancer vaccines, presents a promising avenue for synergistic cancer treatment.

• Emerging multifunctional nanoplatforms that combine ferroptosis induction with other therapeutic modalities, such as photodynamic therapy and photothermal therapy, offer a multifaceted approach to cancer treatment.

• Nanotechnology offers a versatile platform for the targeted delivery of ferroptosis inducers, enabling precise modulation of ferroptosis in cancer cells and the tumor microenvironment.

• Future research should focus on elucidating the intricate interactions between ferroptosis, nanomaterials, and the immune system, as well as developing innovative nanotechnology approaches that can effectively modulate ferroptosis for enhanced cancer immunotherapy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study is supported in parts by a fund from the Basic Research Program of Science and Technology Commission of Shanghai Municipality (21JC1401800), the National Natural Science Foundation of China (31970663, 82173028, 82141105).