Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer.

Chengzhi Huang,Minjia Wang,Qing Zhang,Yue Zhou,Xueqing Yao

doi:10.3389/fonc.2022.827891

Abstract

Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC.

Highlights

The rapid development of cancer therapeutic methods, colorectal cancer (CRC) is still the third most common cancer in the world [1]
CRC patients benefit from the chemotherapy, while patients suffered from chemotherapy resistance
Chemotherapy failure or resistance was the major cause of recurrence and poor prognosis in CRC patients

Summary

Introduction

The rapid development of cancer therapeutic methods, colorectal cancer (CRC) is still the third most common cancer in the world [1]. The early-stage CRC patients may benefit from radical surgical resection with a higher disease-free survival (DFS) rate of nearly 90% [2, 3]. The advanced or metastatic CRC patients might not have the chance to accept the radical surgical resection [3, 4]. Chemotherapy, targeted therapy, or immunotherapy might be a better preferable therapeutic method for those patients. Oxaliplatin (OXA), a Pt-based chemotherapy drug, combined with 5-fluorouracil (5-Fu) or capecitabine was introduced for first-line chemotherapy methods for advanced CRC patients [5, 6]. The overall survival (OS) or DFS for advanced CRC patients remained low.

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Results

Conclusion