Facile Assembly of Thermosensitive Liposomes for Active Targeting Imaging and Synergetic Chemo-/Magnetic Hyperthermia Therapy.

Yanli An,Zhiyuan Zhang,Xihui Wang,Chunmei Hu,Yong Han,Dongfang Liu,Rui Yang,Gang Jia,Qiusha Tang

doi:10.3389/fbioe.2021.691091

Abstract

Cancer stem cells (CSCs) are thought to be responsible for the recurrence of liver cancer, highlighting the urgent need for the development of effective treatment regimens. In this study, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and thermosensitive magnetoliposomes (TMs) conjugated to anti-CD90 (CD90@17-AAG/TMs) were developed for temperature-responsive CD90-targeted synergetic chemo-/magnetic hyperthermia therapy and simultaneous imaging in vivo. The targeting ability of CD90@DiR/TMs was studied with near-infrared (NIR) resonance imaging and magnetic resonance imaging (MRI), and the antitumor effect of CD90@17-AAG/TM-mediated magnetic thermotherapy was evaluated in vivo. After treatment, the tumors were analyzed with Western blotting, hematoxylin and eosin staining, and immunohistochemical (IHC) staining. The relative intensity of fluorescence was approximately twofold higher in the targeted group than in the non-targeted group, while the T2 relaxation time was significantly lower in the targeted group than in the non-targeted group. The combined treatment of chemotherapy, thermotherapy, and targeting therapy exhibited the most significant antitumor effect as compared to any of the treatments alone. The anti-CD90 monoclonal antibody (mAb)-targeted delivery system, CD90@17-AAG/TMs, exhibited powerful targeting and antitumor efficacies against CD90+ liver cancer stem cells in vivo.

Highlights

Tumorigenesis and heterogeneity, progression, and recurrence of tumors are largely caused by a small subpopulation of tumor cells with stem cell properties, known as the cancer stem cells (CSCs) (Chen et al, 2013)
CD90 is an important marker for liver cancer stem cells (LCSCs), and study has shown that the expression of CD90 was related to the formation, growth, metastasis, and drug resistance of liver cancer
The fluorescence intensity reported for tumors from IgG@DiR/thermosensitive magnetoliposomes (TMs) and DiR/TMs group significantly decreased over time

Summary

INTRODUCTION

Tumorigenesis and heterogeneity, progression, and recurrence of tumors are largely caused by a small subpopulation of tumor cells with stem cell properties, known as the cancer stem cells (CSCs) (Chen et al, 2013). Rao et al (2015) developed a doxorubicin-encapsulated polymeric nanoparticle covered with chitosan to target and kill CD44+ mammary cancer stem-like cells This drug delivery system was found to be effective in eliminating cancer stem-like cells, decreasing the tumor volume, and exhibiting low systemic toxicity. The eradication of differentiated cells in tumors may provide a synergetic effect for the clearance of CSCs. CD90 is an important marker for liver cancer stem cells (LCSCs), and study has shown that the expression of CD90 was related to the formation, growth, metastasis, and drug resistance of liver cancer. CD90 is an important marker for liver cancer stem cells (LCSCs), and study has shown that the expression of CD90 was related to the formation, growth, metastasis, and drug resistance of liver cancer This makes the treatment of targeting CD90+ LCSCs of important practical significance (Liu et al, 2020). We collectively studied the targeting property of CD90@17AAG/TMs in HCC-bearing mice and explored the antitumor effect and mechanism of CD90@17-AAG/TMs against CD90+ LCSCs under hyperthermic conditions in vivo

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSION

ETHICS STATEMENT