Developing neobavaisoflavone nanoemulsion suppresses lung cancer progression by regulating tumor microenvironment.
It is necessary to create novel, efficacious and harmless therapeutic strategy for lung cancer treatment. The application of nanoemulsion to specifically suppress cancer progression in the tumor microenvironment would be an effective therapy. Neobavaisoflavone (Neo) is an isoflavone isolated from Psoralea corylifolia L, possesses striking anti-inflammatory and anti-cancer effects. In our stduy, Neo significantly reduced reactive oxygen species (ROS) generation in the activated myofibroblast. Furthermore, a novel Neo nanoemulsion (nano-Neo) was prepared to improve Neo solubility and bioavailability. Nano-Neo showed more effectively anti-proliferative role in lung cancer cells. In addition, in vivo analysis further demonstrated that nano-Neo could effectively suppress tumor growth compared to the free Neo-treated mice without noticeable damage to major organs. Furthermore, nano-Neo treatment markedly reduced extracellular matrix (ECM) deposition in tumor samples by repressing transforming growth factor-β (TGF-β)/SMADs signaling pathway. Meanwhile, the activated immune microenvironment in tumor tissues was dramatically improved by nano-Neo through reducing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) infiltration, as well as improving the count of natural killer (NK) cells and M2 macrophage phenotype switch to pro-inflammatory M1. In addition, we found that the prepared nano-Neo exerted promising tumor targeting efficiency with improved pharmacokinetic properties. Therefore, the novel approach to prepare nano-Neo introduced here might provide an effective strategy for lung cancer treatment with few adverse effects.
['Ye|Hui|H|', 'He|Xiaojie|X|', 'Feng|Xu|X|']
D016475:3T3 Cells D000072283:A549 Cells D000818:Animals D000972:Antineoplastic Agents, Phytogenic D049109:Cell Proliferation D004339:Drug Compounding D004655:Emulsions D005109:Extracellular Matrix D006801:Humans D007529:Isoflavones D008175:Lung Neoplasms D016246:Lymphocytes, Tumor-Infiltrating D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D053758:Nanoparticles D017207:Rats, Sprague-Dawley D015398:Signal Transduction D047368:Tumor Burden D059016:Tumor Microenvironment D000084582:Tumor-Associated Macrophages D023041:Xenograft Model Antitumor Assays
Lung cancer ECM Immune microenvironment Nano-neobavaisoflavone TME