Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies
Abstract
1. Introduction
1.1. Current Status and Challenges of Lung Cancer Treatment
1.2. Therapeutic Potential of SPIONs
1.3. Innovative Value of Biomimetic Strategies
2. Literature Search Strategy
- Studies investigating biomimetic SPIONs (e.g., cell-membrane-camouflaged or other biomimetic strategies) for lung cancer diagnosis or therapy;
- Reports including in vitro cellular or in vivo animal experiments;
- Detailed description of fabrication protocols, mechanisms of action, or therapeutic efficacy;
- Original research articles, reviews, or meta-analyses.
- Conference abstracts, patents, editorials, commentaries, or news reports;
- Studies unrelated to lung cancer or SPIONs;
- Full text unavailable or duplicate publications.
3. Cell-Membrane Camouflage Technology
3.1. Technical Principles
3.2. Preparation and Characterization
3.3. Major Membrane Types and Their Applications
3.3.1. Macrophage Membrane
3.3.2. Neutrophil Membrane
3.3.3. Cancer-Cell Membrane (CCM)
3.3.4. Formulation–Process–Performance Nexus: Toward Reproparable, Scale-Ready Manufacturing
3.4. Tumor Heterogeneity: A Touchstone for Cell-Membrane Camouflage
3.4.1. The Challenge of Heterogeneity—Why “One-Size-Fits-All” No Longer Works
3.4.2. Multi-Receptor Synergy—How Membrane Camouflage Can Fight Back
3.5. Cell-Membrane Camouflage in the Metastatic Cascade: Mechanisms Beyond Homotypic Targeting
4. Strategies for Enhanced Pulmonary Retention
4.1. Pulmonary Vascular Architecture and the Air–Blood Barrier: Biological Constraints on SPIONs Targeting
4.2. Optimization of Magnetic Targeting Systems
4.3. Respiratory-Compensated Magnetic Targeting: Overcoming Lung Motion for Precision SPIONs Accumulation
4.4. Multifunctional Surface Engineering Strategies
5. Therapeutic Applications and Mechanisms
5.1. Strategies and Mechanisms for Overcoming Physiological Barriers
5.2. Synergistic Immunotherapy
6. Translational Medicine Challenges
7. Narrative Comparison: Biomimetic SPIONs vs. Pegylated Liposomes vs. PLGA-PEG Nanoparticles
8. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| CDT | hemodynamic therapy |
| SPIONs | Superparamagnetic iron-oxide nanoparticles |
| MHT | magnetic hyperthermia therapy |
| MRI | magnetic resonance imaging |
| MPI | magnetic particle imaging |
| EPR | enhanced permeability and retention |
| MDR | multidrug resistance |
| NETs | neutrophil extracellular traps |
| GMP | Good Manufacturing Practice |
| PLA-PEG | poly(lactic acid)-poly(ethylene glycol) |
| Tf | transferrin |
| ICD | immunogenic cell death |
| TAMs | tumor-associated macrophages |
| iPSC | induced pluripotent stem cell |
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| Membrane Type | Major Membrane-Protein Components | Targeting Characteristics | Immune-Evasion Capability | Circulation Time | Preparation Difficulty | Application Scenarios | References |
|---|---|---|---|---|---|---|---|
| Macrophage membrane | PSGL-1, LFA-1, VLA-4 | VCAM-1-mediated inflammation/tumor-targeting | Moderate (retains partial self-recognition signals) | Moderate (days) | Moderate | Inflammatory sites, tumor microenvironment targeting | [40,41] |
| Neutrophil membrane | CD11b/CD18, CD62L | Integrin-ICAM-1-mediated blood-air barrier penetration | Strong (natural immune-evasion properties) | Short (hours) | Difficult | Lung targeting, acute inflammation therapy | [42,43,44,45] |
| Cancer-cell membrane | Tumor-specific antigens (e.g., EGFR), integrin αvβ3 | Homologous targeting (same tumor type) | Strong (expresses “don’t-eat-me” signals) | Moderate (days) | Moderate | Primary tumor and metastasis therapy | [49,51] |
| Cell-Membrane Type | Functional Modification | Therapeutic Mechanism | Model | Key Findings | Conclusion | References |
|---|---|---|---|---|---|---|
| Neutrophil membrane | poly(sialic acid)-octadecylamine | Neutrophil-mediated delivery | Mouse lung cancer model | Enhanced drug delivery to lung tumor site | Neutrophil membrane improves lung targeting | [45] |
| Cancer-cell membrane | Curcumin + DOX co-loading | Homologous targeting + MDR reversal | Esophageal cancer model (extensible to lung) | Effective inhibition of drug-resistant tumor growth | CCM enhances tumor-specific accumulation | [51] |
| No membrane (MnO2 shell) | Ce6 photosensitizer + O2 generation | Self-oxygenated PDT + MRI/PA imaging | Mouse lung cancer model | Alleviated hypoxia, enhanced ROS production | Overcomes hypoxia-induced PDT resistance | [56] |
| Neutrophil exosome hybrid | Transferrin (Tf) conjugation | Magnetic targeting + exosome homing | Mouse lung-metastasis model | Enhanced lung accumulation via Tf and neutrophil tropism | Dual targeting improves lung retention | [57] |
| Lung cancer cell membrane | Tumor-associated antigens preserved | Homologous targeting + immune evasion | Mouse lung cancer model | Enhanced tumor enrichment, evaded immune clearance | Cancer membrane improves tumor-specific targeting | [65] |
| Mesoporous silica shell | Fe3O4@mSiO2 core–shell | High paclitaxel loading via mesopores | In vitro/vivo tumor models | Improved hydrophobic drug-loading and release | Mesoporous shell enhances drug compatibility | [66] |
| Hollow SPIONs | Hematoporphyrin + US-triggered H2O2 decomposition | SDT + MHT synergy | Mouse tumor model | Overcame light penetration limit, enhanced deep tumor therapy | Combined SDT-MHT effective for deep tumors | [67] |
| T-cell membrane | SPIONs loaded into human T-cells | T-cell function preservation + magnetic navigation | Human T-cells in vitro | T-cell activation and cytotoxicity unaffected | SPIONs can serve as T-cell carriers for immunotherapy | [68] |
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Liu, Q.; Jiang, L.; Wang, K.; Dai, J.; Liu, X. Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies. Pharmaceutics 2025, 17, 1301. https://doi.org/10.3390/pharmaceutics17101301
Liu Q, Jiang L, Wang K, Dai J, Liu X. Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies. Pharmaceutics. 2025; 17(10):1301. https://doi.org/10.3390/pharmaceutics17101301
Chicago/Turabian StyleLiu, Quanxing, Li Jiang, Kai Wang, Jigang Dai, and Xiaobing Liu. 2025. "Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies" Pharmaceutics 17, no. 10: 1301. https://doi.org/10.3390/pharmaceutics17101301
APA StyleLiu, Q., Jiang, L., Wang, K., Dai, J., & Liu, X. (2025). Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies. Pharmaceutics, 17(10), 1301. https://doi.org/10.3390/pharmaceutics17101301

