A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy

Taiying Chen; Ngalei Tam; Yu Mao; Chengjun Sun; Zekang Wang; Yuchen Hou; Wuzheng Xia; Jia Yu; Linwei Wu

doi:10.1016/j.mtbio.2022.100338

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy

Mater Today Bio. 2022 Jun 23:16:100338. doi: 10.1016/j.mtbio.2022.100338. eCollection 2022 Dec.

Authors

Taiying Chen^{1

2

3}, Ngalei Tam⁴, Yu Mao^{1

2

3}, Chengjun Sun^{1

2}, Zekang Wang^{1

2}, Yuchen Hou⁵, Wuzheng Xia^{1

2

3}, Jia Yu⁶, Linwei Wu^{1

2

3}

Affiliations

¹ Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
² School of Medicine, South China University of Technology, Guangzhou, 510006, China.
³ Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
⁴ Office of Organ Transplant Management, The Fifth Affiliated Hospital of Sun Yat- Sen University, Zhuhai, 519099, China.
⁵ Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai, 200127, China.
⁶ Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Abstract

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O₂ generation by catalyzing tumor over-expressed H₂O₂, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Keywords: Dual-modal imaging; Hepatocellular carcinoma; In situ oxygen supplement; Stimuli-responsive drug release; Tumor microenvironments.