Harnessing tumor microenvironment immunocytes: nanomedicine strategies for lung cancer therapy

Lung cancer, with high global mortality, requires more precise therapies. The tumor microenvironment (TME) promotes immune evasion, disease progression, and treatment resistance, while nanomedicine targeting immune cells provides a promising approach to reprogram the immunosuppressive TME and enhance anti-tumor immunity. Currently, nanomedicines have flourished in terms of targeting strategies, drug design, and material selection, yet systematic discussion of their mechanisms and efficacy is still lacking. Meanwhile, the clinical translation of nanotherapeutic strategies faces numerous challenges.

A medical research team led by Professor Qiang Li from Tongji University in China recently outlined the current status of research on lung cancer nanomedicines targeting immune cells to advance research progress in this field. Immune cells in the TME exhibit complex phenotypic regulation and functional crosstalk, which not only act as key drivers of lung cancer immune evasion but also serve as core breakthrough points for novel lung cancer treatment strategies. Targeting immune cells as core therapeutic targets will provide a key direction for lung cancer nanotherapeutic strategies to improve therapeutic efficacy and facilitate clinical translation.

The team published their review in Nano Research on January 22, 2026.

“In this review, we systematically summarize the design rationales, targeting mechanisms, and therapeutic merits of nanomaterials that target key immune cells in the lung cancer TME. We also dissect the challenges currently hindering the clinical translation of lung cancer nanomedicines, and aim to lay a theoretical foundation and provide practical guidance for advancing the development of nano-immunotherapy for lung cancer,” said Qiang Li, senior author of the review paper and professor of clinical medicine at the Eastern Hospital Affiliated to Tongji University. Professor Li also serves as Chairman of the Interventional Respiratory Disease Committee of the Respiratory Branch of the Chinese Medical Doctor Association and Deputy Leader of the Lung Cancer Study Group of the Respiratory Disease Branch of the Chinese Medical Association.

The research team systematically collated the functional roles of various immune cells in the lung cancer TME and their impacts on therapeutic efficacy. Antigen-presenting cells (APCs), such as dendritic cells (DCs), participate in tumor antigen presentation and T-cell activation, and exert regulatory effects on tumor cell killing mediated by cytotoxic T lymphocytes (CTLs). In contrast, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and other immunosuppressive cells inhibit the functions of anti-tumor immune cells through multiple pathways, contributing to the formation of an immunosuppressive TME and acting as key drivers of tumor immune evasion and therapeutic resistance. “Traditional therapies lack precise targeting ability and cannot selectively modulate the phenotypes and functions of immune cells in the TME, while the rise of nanomedicines has provided an effective solution to address this dilemma,” said Li Qiang.

With diverse material options and high editability, nanomedicines exert precise effects on the TME via two core targeting modes: passive targeting enrichment based on the enhanced permeability and retention (EPR) effect and active targeting recognition based on ligand modification. Their main mechanisms of action include: promoting the exposure of tumor-associated antigens and activating APC functions to further strengthen anti-tumor immunity mediated by CTLs and other effector cells; inhibiting the functions of immunosuppressive cells such as Tregs and MDSCs; and inducing the polarization of TAMs and TANs toward anti-tumor phenotypes. In addition, the organic integration of immune cells and nanomedicines is reflected in the use of immune cell internalization for delivery or immune cell membrane coating to further improve the targeted delivery efficiency of drugs.

Based on immune cell-targeting strategies, nanomedicines have not only significantly improved the precision and efficacy of anti-tumor therapy, but also served as a bridge for realizing combined regimens of traditional therapies (e.g., chemotherapy, targeted therapy) and novel therapeutic modalities (e.g., photothermal therapy, photodynamic therapy, sonodynamic therapy). However, challenges inherent to the lung cancer TME, such as cellular heterogeneity, unpredictable biological behaviors of nanocarriers, and the lack of long-term efficacy and toxicological data, still severely hinder the clinical translation of nanotherapeutic strategies.

The team systematically sorted out the regulatory mechanisms of immune cells in the TME and related nanomedicine targeting strategies, clarified the key value of immune cells as therapeutic targets, and provided a reference for breaking through the bottlenecks in the research and development and clinical translation of lung cancer nanomedicines. “Through in-depth analysis of the underlying mechanisms and efficacy of existing immune cell-targeted nanomedicine strategies, and focused efforts on addressing the key pain points in clinical translation, we believe that nanomedicines will surely bring promising outcomes to lung cancer treatment in the future,” said Li Qiang.

Other contributors include Wei Gao, Jing Gao, Yu Feng, Di Wu, Ximing Liao, Jialin Yao, Tian Li, Muyun Wang, and Kun Wang from the Eastern Hospital Affiliated to Tongji University.

This work was supported by National Natural Science Foundation of China (grant number: 82570119), the Natural Science Foundation of Shanghai (grant number: 25ZR1402443), Healthcare Talents Youth Program of Shanghai Pudong New Area (grant number: 2025PDWSYCQN-02) for Wei Gao; National Natural Science Foundation of China (grant number: 82270116) for Qiang Li; National Natural Science Foundation of China (grant number: 82470073), Shanghai science and technology development funds (grant number: 24QA2707100) for Kun Wang.

DOI Link:

https://doi.org/10.26599/NR.2025.94908300

About Nano Research

Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.