Antitumor activity of anti-miR-21 delivered through lipid nanoparticles.

The ability of lipid nanoparticles (LNPs) to deliver nucleic acids had shown a great therapeutic potential to treat a variety of diseases. Here, an optimized formulation of QTsome lipid nanoparticle (QTPlus) was utilized to deliver an anti-miR-21 (AM21) against cancer. The miR-21 downstream gene regulation and antitumor activity was evaluated using mouse and human cancer cells and macrophages. The antitumor activity of QTPlus encapsulating AM21 (QTPlus-AM21) was further evaluated in combination with erlotinib and atezolizumab (ATZ). QTPlus-AM21 demonstrated a superior miR-21-dependent gene regulation and eventually inhibited A549 non-small cell lung cancer growth in vitro. QTPlus-AM21 further induced chemo-sensitization of A549 cells to erlotinib with a combination index of 0.6 in inhibiting A549 cell growth. When systemically administered to MC38 tumor-bearing mouse model, QTPlus-AM21 exhibited an antitumor immune response with over 80% tumor growth inhibition (TGI%) and over 2-fold and 4-fold PD-1 and PD-L1 upregulation in tumors and spleens. The combination therapy of QTPlus-AM21 and ATZ further showed a higher antitumor response (TGI% over 90%) and successfully increased M1 macrophages and CD8 T cells into TME. This study provides new insights into the antitumor mechanism of AM21 and showed great promise of QTPlus-AM21 in combination with chemotherapies and immunotherapies. This article is protected by copyright. All rights reserved.