Cancer immune therapy using engineered ‛tail-flipping' nanoliposomes targeting alternatively activated macrophages

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Immunotherapy

Background:

• Alternatively-activated, M2-like tumor-associated macrophages (TAMs) promote tumor progression, invasiveness, and metastasis.
• Targeting pro-tumorigenic TAM functions is a key strategy in cancer immunotherapy research.

Purpose of the Study:

• To develop engineered nanoliposomes capable of specifically targeting and delivering payloads to M2-like TAMs.
• To investigate the mechanism of nanoliposome uptake by M2 macrophages via scavenger receptors.

Main Methods:

• Designing nanoliposomes with specific phospholipid compositions to mimic peroxidated phospholipids.
• Utilizing molecular dynamics simulations and molecular docking to predict lipid bilayer behavior and receptor interactions.
• In vivo administration of engineered nanoliposomes loaded with therapeutic agents (STAT6 inhibitor, zoledronic acid, muramyl tripeptide) in a pre-clinical cancer model.

Main Results:

• Engineered nanoliposomes were specifically internalized by M2 macrophages through scavenger receptors, particularly SR-B1.
• The nanoliposomes effectively delivered payloads to M2-like TAMs in vivo.
• Treatment with loaded nanoliposomes led to the reduction of the premetastatic niche and/or tumor growth.

Conclusions:

• Demonstrated the efficacy and versatility of "tail-flipping" nanoliposomes for targeting M2-like TAMs.
• This nanotechnology platform shows promise for developing novel cancer immunotherapeutics.