Engineered nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression

Area of Science:

• Oncology
• Nanomedicine
• Immunology

Background:

• The tumor microenvironment (TME) often suppresses anti-cancer immunity.
• Inflammation and immunosuppressive cells within the TME hinder effective cancer treatment.

Purpose of the Study:

• To engineer novel chimeric nanomicelles (NMs) combining docetaxel (DTX) and dexamethasone (DEX).
• To evaluate the efficacy of DTX-DEX NMs in altering the immunosuppressive TME and enhancing anti-cancer activity.

Main Methods:

• Self-assembly of phospholipid-DTX and PEGylated-lipid-DEX conjugates into sub-100 nm chimeric NMs.
• Assessment of anti-cancer activity in syngeneic and xenograft mouse models.
• Analysis of immune cell populations, cytokine expression, and prostaglandin synthesis within the TME.

Main Results:

• DTX-DEX NMs demonstrated superior tumor regression and enhanced mouse survival compared to other treatments.
• NMs significantly reduced myeloid-derived suppressor cells and modulated macrophage polarization.
• Accumulation of cytotoxic CD4+ and CD8+ T cells was enhanced, alongside altered cytokine profiles.
• Inhibition of prostaglandin synthesis, particularly PGE2, by targeting cyclooxygenase 2 was observed.

Conclusions:

• Lithocholic acid-derived chimeric NMs effectively reprogram the immunosuppressive TME.
• DTX-DEX NMs offer a promising strategy for cancer treatment by modulating the prostaglandin pathway and boosting anti-tumor immunity.
• This approach leads to mitigated tumor progression and improved survival outcomes.