Ultrasound-visualized nanocarriers with siRNA for targeted inhibition of M2-like TAM polarization to enhance photothermal therapy in NSCLC
Wenhao Lv, Xu Chen, Hao Wu, Yangyang Zhu, Ozioma Udochukwu Akakuru, Hui Du, Fang Nie, Aiguo Wu, Juan Li
Abstract
Photothermal therapy (PTT) has received a lot of attention as a promising strategy for eliminating tumors quickly. However, the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages (TAMs), increasing the risk of tumor recurrence and metastasis. To address this problem, gold-based nanocarriers (PGMP-small interfering RNA (siRNA) nanoparticles (NPs)) containing STAT6siRNA, that inhibited M2-like TAM polarization, were designed and investigated for PTT and gene therapy of non-small cell lung cancer (NSCLC). In an NSCLC model, the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90% in macrophages, thus inhibiting the polarization of about 87% of M2-like TAMs and effectively suppressing the invasion and metastasis of NSCLC. Meanwhile, the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging, thus contributing to the efficient elimination and real-time monitoring of the tumor tissues. These nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment, and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.