International Journal of Nanomedicine (Mar 2021)
Self-Monitoring and Self-Delivery of Self-Assembled Fluorescent Nanoparticles in Cancer Therapy
Abstract
Hongmei Liu,1,2 Minghao Yuan,1,2 Yushi Liu,1,2 Yiping Guo,3 Haijun Xiao,4 Li Guo,1,2 Fei Liu1,2 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu, 611137, People’s Republic of China; 3Quantitative and Systems Biology Program, University of California, Merced, CA, 95343, USA; 4Centre of Polymer Systems, Tomas Bata University in Zlin, Zlin, 76001, Czech RepublicCorrespondence: Li GuoChengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of ChinaTel +86 28-61800237Email [email protected]: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer.Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity.Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions.Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles’ self-monitoring function has been developed, opening up new ideas for combined tumor therapy.Keywords: carrier-free, irinotecan hydrochloride, curcumin, multifunctional nanoparticles
