Novel Peptide-Modified Zeolitic Imidazolate Framework-8 Nanoparticles with pH-Sensitive Release of Doxorubicin for Targeted Treatment of Colorectal Cancer

• Published in: Pharmaceutics Vol. 17; no. 2; p. 246
• Main Authors: Gong, Liming, Zhao, Heming, Chen, Liqing, Liu, Yanhong, Wu, Hao, Liu, Chao, Feng, Jing, Liu, Chenfei, Xiao, Congcong, Wang, Qiming, Jin, Mingji, Gao, Zhonggao, Huang, Wei, Guan, Youyan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2025; MDPI
• Subjects: Adjuvant treatment; Apoptosis; Biocompatibility; Cancer; Cell culture; Colorectal cancer; doxorubicin; Drug delivery systems; Drug therapy; Gastrointestinal diseases; Hemodialysis; Hydrogen-ion concentration; Ligands; LT peptide; Nanoparticles; NMR; Nuclear magnetic resonance; Particle size; Peptides; pH-sensitive release; Polyethylene glycol; targeted tumor therapy; Toxicity; Tumors; zeolitic imidazolate framework-8; Zinc; Massachusetts; China; California; Beijing China; United States > US; Shanghai China; LT peptide; colorectal cancer; doxorubicin; zeolitic imidazolate framework-8; targeted tumor therapy; pH-sensitive release
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics17020246

: Colorectal cancer (CRC) is one of the common malignant tumors. Chemotherapeutic agents represented by doxorubicin (DOX) are common adjuvant therapies for patients with advanced CRC. However, DOX suffers from dose-dependent cardiotoxicity and myelosuppression due to a lack of targeting and specificity, which severely limits its clinical application. : Herein, we constructed a zeolitic imidazolate framework-8 (ZIF-8) modified by a novel peptide (LT peptide) to deliver the chemotherapeutic drug doxorubicin (DOX) for the targeted treatment of CRC. : In this study, LT-PEG@DOX@ZIF-8 nanoparticles were prepared by a simple method with suitable particle size and zeta potential, which were also capable of pH-responsive drug release. In vitro assays exhibited that LT-PEG@DOX@ZIF-8 nanoparticles were effectively taken up by C26 cells, significantly inhibited cell proliferation, and induced apoptosis. Furthermore, in mice models with colorectal tumors, LT-PEG@DOX@ZIF-8 nanoparticles also displayed specific tumor aggregation and exerted anti-tumor effects to prolong the survival of the mice. : In conclusion, LT-PEG@DOX@ZIF-8 provides a promising strategy for the delivery of DOX to effectively treat CRC.