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用于乳腺癌治疗中阿霉素和CpG共递送的新型聚乙二醇化壳聚糖纳米载体:制备、表征及免疫治疗潜力

Innovative PEGylated chitosan nanocarriers for co-delivery of doxorubicin and CpG in breast cancer therapy: Preparation, characterization, and immunotherapeutic potential.

作者信息

Alharthi Sitah, Alrashidi Amal Abdullah, Ziora Zyta, Ebrahimi Shahmabadi Hasan, Alavi Seyed Ebrahim

机构信息

Department of Pharmaceutics, College of Pharmacy, Shaqra University, Al-Dawadmi Campus, 11961, Al-Dawadmi, Saudi Arabia.

Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, 11671, Riyadh, Saudi Arabia.

出版信息

Med Oncol. 2025 Apr 23;42(5):176. doi: 10.1007/s12032-025-02714-4.

DOI:10.1007/s12032-025-02714-4
PMID:40266471
Abstract

This study aimed to design polyethylene glycol (PEG)ylated chitosan (CS, PEG-CS) nanoparticles for the co-delivery of doxorubicin (DOX), cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and ovalbumin (OVA) to enhance breast cancer therapy. PEG-CS nanoparticles were synthesized using the ionotropic gelation method and characterized for size, zeta potential (ZP), entrapment efficiency, and drug release. In vitro and in vivo studies were conducted to assess cytotoxicity, immune activation, and antitumor efficacy. The optimized nanoparticles had a mean diameter of 156.4 ± 8.9 nm, a ZP of +18 mV, and demonstrated 75.3% DOX and 68.3% CpG release over 72 h. PEG-CS-DOX/CpG/OVA enhanced tumor reduction by 2.6-fold in vivo, with no significant toxicity. PEG-CS-DOX/CpG/OVA nanoparticles showed promise as a co-delivery platform for cancer therapy, combining cytotoxic and immune-stimulating effects with minimal toxicity.

摘要

本研究旨在设计聚乙二醇(PEG)化壳聚糖(CS,PEG-CS)纳米颗粒,用于共递送阿霉素(DOX)、胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸(CpG)和卵清蛋白(OVA),以增强乳腺癌治疗效果。采用离子凝胶法合成PEG-CS纳米颗粒,并对其粒径、zeta电位(ZP)、包封率和药物释放进行表征。进行体外和体内研究以评估细胞毒性、免疫激活和抗肿瘤疗效。优化后的纳米颗粒平均直径为156.4±8.9nm,ZP为+18mV,在72小时内DOX释放率为75.3%,CpG释放率为68.3%。PEG-CS-DOX/CpG/OVA在体内使肿瘤缩小增强了2.6倍,且无明显毒性。PEG-CS-DOX/CpG/OVA纳米颗粒有望作为一种癌症治疗的共递送平台,将细胞毒性和免疫刺激作用相结合,同时毒性最小。

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