<p>Multifunctional Nanoparticles Encapsulating Astragalus Polysaccharide and Gold Nanorods in Combination with Focused Ultrasound for the Treatment of Breast Cancer</p>

Abstract

Purpose: Focused ultrasound (FUS) is a noninvasive method to produce thermal and mechanical destruction along with an immune-stimulatory effect against cancer. However, FUS ablation alone appears insufficient to generate consistent antitumor immunity. In this study, a multifunctional nanoparticle was designed to boost FUS-induced immune effects and achieve systemic, long-lasting antitumor immunity, along with imaging and thermal enhancement. Materials and Methods: PEGylated PLGA nanoparticles encapsulating astragalus polysaccharides (APS) and gold nanorods (AuNRs) were constructed by a simple double emulsion method, characterized, and tested for cytotoxicity. The abilities of PA imaging and thermal-synergetic ablation efficiency were analyzed in vitro and in vivo. The immunesynergistic effect on dendritic cell (DC) differentiation in vitro and the immune response in vivo were also evaluated. Results: The obtained APS/AuNR/PLGA-PEG nanoparticles have an average diameter of 255.00±0.1717 nm and an APS-loading efficiency of 54.89±2.07%, demonstrating their PA imaging capability and high biocompatibility both in vitro and in vivo. In addition, the asprepared nanoparticles achieved a higher necrosis cell rate and induced apoptosis rate in an in vitro cell suspension assay, greater necrosis area and decreased energy efficiency factor (EEF) in an in vivo rabbit liver assay, and remarkable thermal-synergic performance. In particular, the nanoparticles upregulated the expression of MHC-II, CD80 and CD86 on cocultured DCs in vitro, followed by declining phagocytic function and enhanced interleukin (IL)-12 and interferon (INF)-γ production. Furthermore, they boosted the production of tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, and IgG1 (P< 0.001) but not IgG2a. Immune promotion peaked on day 3 after FUS in vivo. Conclusion: The multifunctional APS/AuNR/PLGA-PEG nanoparticles can serve as an excellent synergistic agent for FUS therapy, facilitating real-time imaging, promoting thermal ablation effects, and boosting FUS-induced immune effects, which have the potential to be used for further clinical FUS treatment.

Metallic Nanoparticles for the Modulation of Tumor Microenvironment; A New Horizon

“…CeNPs have presented a powerful redox property through witching the oxidation state of Ce3+ and Ce4+ ( Wang et al, 2009 ; Tsai et al, 2013 ). According to previous studies CeNPs can modulate ROS state through catalase- and superoxide dismutase (SOD)-like activity ( Choi et al, 2007 ; Xiong et al, 2020 ). Filippi et al have reported that CeNPs exert high ·OH scavenging activity in both phosphate buffered saline and surrogate lung fluid ( Shanmugam et al, 2014b ).…”

Green synthesis and characterization of gold nanoparticles from Pholiota adiposa and their anticancer effects on hepatic carcinoma

“…Numerous studies have demonstrated the green synthesis of AuNPs using TCM polysaccharides and extracts such as Marsdenia tenacissima , Ulva intestinalis L. aqueous, and Encapsulating Astragalus, among others, can inhibit tumor cell proliferation (Li et al., 2019 ; González-Ballesteros et al., 2019 ; Xiong et al., 2020 ). Because PAP-1a regulates the immune system and has indirect anticancer actions in liver cancer, AuNPs may enhance PAP-1a's biocompatibility.…”

Inhibitory Effects of Astragalus Polysaccharide on Proliferation of Human Lung Adenocarcinoma H1299 Cells via the Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Signaling Pathway

“…With advocating the modernization of traditional Chinese medicine nowadays, as the main active constituent of Astragalus, APS with anti-virus, anti-tumor, anti-aging, anti-radiation, anti-stress and anti-oxidation effects has been paid more attention [10,11] . APS-assisted chemotherapy, as reported, can enhance tumor suppression, reduce toxic and side effects, reinforce the body's cellular immune function and improve the quality of life of patients with tumors [12] . This study aimed to verify the inhibitory effect of APS on tumor cell invasion and metastasis and to explore its molecular mechanism.…”