Nebulized macrophage membrane-engineered triptolide liposomes for Siglec-10/CD24-mediated therapeutic targeting in
Ting Zhou1, Chuan Wang1,2, Yayuan Liu3
1State Key Laboratory of Southwestern Chinese Medicine Resources, Lab for Innovation & Effective Uses of Chinese Drug Germplasm Resources, School of Pharmacy, College of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Abstract:
Non-small cell lung cancer (NSCLC) currently stands as the predominant etiological factor underlying lung cancer-related mortality on a global scale. Conventional drug delivery methods are associated with significant toxic side effects, highlighting the necessity to develop novel targeted delivery systems to improve the therapeutic efficacy of lung cancer treatment. Here, we aimed to develop a pulmonary drug delivery system for triptolide (TP) to treat orthotopic lung cancer. Herein, triptolide-loaded liposomes (TP-lip) were prepared to reduce the toxicity and improve the solubility of triptolide. Macrophage membranes (MM), rich in Siglec-10, were engineered onto the liposomes to enhance the tumor targeting through specific binding to Cluster of differentiation 24 (CD24), a molecule overexpressed on lung tumor cells. Regardless of macrophage polarization, the high Siglec-10 expression on cell membranes ensures effective tumor cell targeting. After modifying different types of MMs on TP-lip and nebulizing them, the aerodynamic fine particle fraction (FPF) of TP formulations exceeded 50%, and the mass median aerodynamic diameter (MMAD) was below 5 μm, suitable for pulmonary delivery. MM-modified liposomes showed higher cellular uptake and stronger inhibitory effects on LLC lung tumor cells. Pharmacokinetic studies showed that intratracheal administration (aerosolized drug delivery) of MM-lip could reduce the systemic drug exposure compared to intravenous injection, while achieving effective accumulation in lung tissues. Pulmonary delivery of M0-TP-lip significantly enhanced the anti-tumor efficacy and improved the lifespan of orthotopic lung tumor-bearing mice, with no apparent systemic toxicity observed. Overall, this highlights the potential of inhalable, biomimetic triptolide loaded liposomes for pulmonary tumor treatment through Siglec-10-mediated targeting.
Insights
This study developed inhalable liposomes loaded with triptolide (TP) for non-small cell lung cancer (NSCLC). Macrophage membranes enhanced targeting, improving anti-tumor efficacy and reducing systemic toxicity in mice.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
- Conventional treatments for NSCLC often cause severe side effects.
- Targeted drug delivery systems are needed to improve NSCLC treatment efficacy.
Purpose of the Study:
- To develop an inhalable drug delivery system for triptolide (TP) to treat orthotopic lung cancer.
- To engineer triptolide-loaded liposomes (TP-lip) with macrophage membranes (MM) for enhanced tumor targeting.
- To evaluate the efficacy and safety of pulmonary TP delivery for NSCLC.
Main Methods:
- Triptolide-loaded liposomes (TP-lip) were prepared and modified with macrophage membranes (MM).
- The aerodynamic properties of the MM-modified TP-lip were assessed for pulmonary delivery.
- In vitro cellular uptake and anti-tumor effects on lung cancer cells were evaluated.
- Pharmacokinetic studies and in vivo anti-tumor efficacy in orthotopic lung tumor-bearing mice were conducted.
Main Results:
- MM-modified TP-lip formulations exhibited suitable aerodynamic properties (FPF >50%, MMAD <5 μm) for pulmonary delivery.
- MM-modified liposomes demonstrated enhanced cellular uptake and potent inhibitory effects on lung tumor cells.
- Intratracheal administration of MM-lip reduced systemic drug exposure while increasing lung tissue accumulation.
- Pulmonary delivery of M0-TP-lip significantly improved anti-tumor efficacy and survival in mice with no observed systemic toxicity.
Conclusions:
- Inhalable, biomimetic triptolide-loaded liposomes show promise for pulmonary NSCLC treatment.
- Siglec-10 mediated targeting via macrophage membranes enhances anti-tumor activity.
- This novel delivery system offers a potentially safer and more effective approach to NSCLC therapy.
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