Enhanced Antitumor Efficacy and Reduced Toxicity in Colorectal Cancer Using a Novel Multifunctional Rg3- Targeting Nanosystem Encapsulated with Oxaliplatin and Calcium Peroxide

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Date 2025 Jan 29

PMID 39877588

Authors

Yizhuo Xie

Ming Zhu

Han Bao

Kejia Chen

Shanshan Wang

Jingwen Dai

Hongzhu Chen

He Li

Qi Song

Xinlu Wang

Liangping Yu

Jin Pei

Affiliations

Soon will be listed here.

Abstract

Purpose: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Oxaliplatin (OXA) is currently the primary chemotherapeutic agent for CRC, but its efficacy is limited by the tumor microenvironment (TME). Here, we present a combined approach of chemotherapy and TME modulation for CRC treatment. A multifunctional nanosystem (Rg3-Lip-OXA/CaO) was established using Ginsenoside Rg3 liposomes targeting glucose transporter 1 overexpressed on the surface of CRC cells to co-deliver OXA and calcium peroxide (CaO).

Methods: The CaO nanoparticles were synthesized via the CaCl-HO reaction under alkaline conditions and characterized using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). Rg3-Lip-OXA/CaO was prepared through a thin-film hydration approach and characterized; additionally, its stability and release behavior were studied. The O, HO, and Ca generation ability of Rg3-Lip-OXA/CaO in solution and HCT116 cells were measured. The in vitro cellular uptake was observed via fluorescence microscope and flow cytometry. In vitro cytotoxicity was evaluated using the CCK-8 assay, flow cytometry, and live/dead cell staining. The in vivo targeting effect as well as antitumor efficacy were determined in HCT116 tumor-bearing mice. Finally, the acute toxicity of Rg3-Lip-OXA/CaO was investigated in ICR mice to explore its safety.

Results: The XRD and XPS analyses confirmed the successful synthesis of CaO nanoparticles. The Rg3-Lip-OXA/CaO exhibited an average particle size of approximately 92.98 nm with good stability and sustained release behavior. In vitro and in vivo studies confirmed optimal targeting by Rg3-Lip and demonstrated that the nanosystem effectively produced O, HO and Ca, resulting in significant cytotoxicity. Additionally, in vivo studies revealed substantial tumor growth suppression and reduced tumor-associated fibroblasts (TAFs) and collagen. Acute toxicity studies indicated that Rg3-Lip-OXA/CaO markedly reduced the toxicity of chemotherapeutic drugs.

Conclusion: This multifunctional nanosystem enhances chemotherapy efficacy and reduces toxicity, offering a promising approach for optimizing CRC treatment and potential clinical application.

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