Berberine-loaded Janus gold mesoporous silica nanocarriers for chemo/radio/photothermal therapy of liver cancer and radiation-induced injury inhibition

Abstract

Background:

The combination of chemotherapy with radiotherapy serves as a common therapeutic strategy in clinics. However, it is unsatisfactory due to its poor therapeutic efficiency and severe side-effects originating from chemotherapy-exerted systemic toxicity as well as radiation-induced injury.

Purpose:

Hence, Berberine (Ber), an isoquinolin alkaloid with low toxicity and protective effects against radiotherapy, was used as a novel chemotherapeutic agent for chemo-radiotherapy of liver cancer.

Patients and methods:

We preloaded Ber into folic acid targeting Janus gold mesoporous silica nanocarriers (FA-JGMSNs) for overcoming the poor bioavailability of Ber. Furthermore, FA-JGMSNs were not only employed as radiosensitizers for expanding radiotherapeutic effect, but also used as photothermal agents for supplementing chemo-radiotherapeutic effect by local photothermal therapy.

Results:

In vitro and in vivo experiemtal results demonstrated the highly efficient anti-tumor effect, good biosafety as well as the effective protection of normal tissue of this nanoplatform.

Conclusion:

Based on its superb performance, we believe our work provided a feasible strategy for triple-therapies of liver cancer.

Keywords:

• Berberine
• chemotherapy
• radio-sensitization
• Au MSNs
• Janus
• photothermal therapy

Acknowledgments

This work was supported by the National Key R&D Program of China (Grant no. 2017YFF0108600, 2017YFC0211900 and 2016YFF0103800), the National Natural Science Foundation of China (Grant no. 81771982, 61535010, 8160071152 and 21803075), Key Research Program of the Chinese Academy of Sciences (No. KFZD-SW-210), the Natural Science Foundation of Jiangsu Province (No. BE2015601), and the Natural Science Foundation of Jiangsu Province (Grant no BK20181236).

Disclosure

The authors report no conflicts of interest in this work.

Supplementary Materials

Tetrachloroauric acid (HAuCl₄·3H₂O), cetyltrimethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), Sulforhodamine B (SRB), Hoechst 33,258, 3-Aminopropyltriethoxysilane (APS), sodium borohydride (NaBH₄), and fluorescein isothiocyanate (FITC) were obtained from Sigma-Aldrich Inc (St. Louis, MO, USA). Sodium hydroxide (NaOH), ammonium hydroxide (NH₄OH, 28%), ammonium Nitrate (NH₄NO₃), anhydrous ethanol, hydrochloric acid and succinic anhydride were obtained from Beijing Chemical Reagent Co. (Beijing, People's Republic of China). Bernerine (>99%) was purchased from Shanghai Hualan Chemical Co. (Shanghai, People's Republic of China). FA-PEG-NH2 (MW =3400) were purchased from Xi’an Ruixi (Xi’an, China). RPMI-1640 medium was purchased from GIBCO (Carlsbad, CA, USA). Fetal bovine serum (FBS) were obtained from Beyotime Institute of Biotechnology (Jiangsu, People's Republic of China). Diagnostic kits for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CRE) were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, People's Republic of China). DAO ELISA Kit and iFABP ELISA Kit were purchased from Shanghai Chunmai biotechnology co. (Shanghai, People's Republic of China). All reagents were commercially available products with analytical grade purity and used without further purification.