Citation: Linjie Ju, Zhongxi Huang, Qian Shen, Chan Fu, Shuanghe Li, Wenjie Duan, Chenfeng Xu, Weizhen An, Zhiqiang Zhai, Jifu Wei, Changmin Yu, Guoren Zhou. Glutathione depletion based Pt(Ⅳ) hybrid mesoporous organosilica delivery system to conquer cisplatin chemoresistance: A “one stone three birds” strategy[J]. Chinese Chemical Letters, ;2024, 35(10): 109450. doi: 10.1016/j.cclet.2023.109450 shu

Glutathione depletion based Pt(Ⅳ) hybrid mesoporous organosilica delivery system to conquer cisplatin chemoresistance: A “one stone three birds” strategy

Linjie Ju ^{a, 1} ,
Zhongxi Huang ^{b, 1} ,
Qian Shen ^b ,
Chan Fu ^b ,
Shuanghe Li ^a ,
Wenjie Duan ^a ,
Chenfeng Xu ^b ,
Weizhen An ^b ,
Zhiqiang Zhai ^d ,
Jifu Wei ^{a, *,} ,
Changmin Yu ^{b, *,} ,
Guoren Zhou ^{c, *,}

a.
Department of Pharmacy, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China
b.
Key Laboratory of Flexible Electronics (KLOFE), School of Flexible Electronics (Future Technologies) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, China
c.
Department of Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China
d.
Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, China

weijifu@njmu.edu.cn

iamcmyu@njtech.edu.cn

zhouguoren888@163.com

Received Date: 21 November 2023
Revised Date: 18 December 2023
Accepted Date: 20 December 2023
Available Online: 31 December 2023

Figures(5)

The occurrence of acquired resistance to cisplatin (DDP) that induces the toxic drug effects has always been a huge challenge and urgently needs to be resolved in the cancer treatment. The combination of anticancer drugs with different mechanisms can remarkably improve the chemotherapeutic efficiency. Given that glutathione (GSH) plays as the driving factors in the resistance of DDP, here we have firstly proposed a “three birds, one stone” based nanoplatform to achieve triple synergetic effects simultaneously addressing DDP resistance in non-small cell lung cancer (NSCLC). Specifically, we initially designed and synthesized a DDP prodrug [Pt(Ⅳ)] bridged silsesquioxane precursor (Pt-Si). Then Pt-Si and bis[3-(triethoxysilyl)propyl]diselenide (BTESePD) were integrated into the framework of mesoporous organosilica nanoparticles (MONs) to obtain a nanocarrier MON_Pt/Se. After loading with norcantharidin (NCTD) and modifying with the aptamer AS1411 based G-quadruplex (Apt), the Apt@NCTD@MON_Pt/Se exhibit impressive tumor homing capability. Once being endocytosed, (Ⅰ) the diselenide and -O-Pt(Ⅳ)-O- rich scaffold can be reduced by the excessive GSH, followed by (Ⅱ) breaking the redox homeostasis via GSH depletion and precise release of the DDP. Next, the encapsulated NCTD is also released along with the degradation of the nanocarriers thereby (Ⅲ) achieving the GSH depletion and synergistic anti-tumor effect of NCTD and DDP. Taken together, we believe this “one stone, three birds” strategy may be a promising paradigm to conquer drug resistance for clinical care.
- MON_pt/se,
- NSCLC,
- Glutathione depletion,
- Responsive biodegradation,
- Traditional Chinese medicines,
- Synergistic therapy
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