A carrier-free supramolecular nano-twin-drug for overcoming irinotecan-resistance and enhancing efficacy against colorectal cancer

• Published in: Journal of nanobiotechnology 2023-10, Vol.21 (1), p.1-393, Article 393
• Main Authors: Yuan, Miaomiao, Chen, Tong, Jin, Lu, Zhang, Peng, Xie, Luoyijun, Zhou, Shuyi, Fan, Lianfeng, Wang, Li, Zhang, Cai, Tang, Ning, Guo, LiHao, Xie, Chengmei, Duo, Yanhong, Li, Ling, Shi, Leilei
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Anticancer properties; Antimitotic agents; Antineoplastic agents; Apoptosis; Cancer; Cancer therapies; Carrier-free; Cell death; Chemical properties; Chemoresistance; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Complications and side effects; Cytotoxicity; Damage; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Drug delivery systems; Drug resistance; Drug therapy; Drugs; Effectiveness; Fourier transforms; Genomes; Health aspects; Hydrogen; Hydrogen bonding; Hydrogen bonds; Investigations; Irinotecan; Irinotecan-resistance; Medicin och hälsovetenskap; Metastasis; Methods; Monosaccharides; MRP1 protein; Nano-twin-drug; Nanoparticles; Pharmaceutical research; Poly(ADP-ribose) polymerase; Repair; Ribose; Scientific equipment and supplies industry; Self-assembly; Simulation; Spectrum analysis; Sugars; Supramolecular self-assembly; Toxicity; Tumors; Vehicles
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-02157-x

Irinotecan (Ir) is commonly employed as a first-line chemotherapeutic treatment for colorectal cancer (CRC). However, tremendous impediments remain to be addressed to surmount drug resistance and ameliorate adverse events. Poly-ADP-Ribose Polymerase (PARP) participates in the maintenance of genome stability and the repair of DNA damage, thus playing a critical role in chemotherapy resistance. In this work, we introduce a novel curative strategy that utilizes nanoparticles (NPs) prepared by dynamic supramolecular co-assembly of Ir and a PARP inhibitor (PARPi) niraparib (Nir) through π-π stacking and hydrogen bond interactions. The Ir and Nir self-assembled Nano-Twin-Drug of (Nir-Ir NPs) could enhance the therapeutic effect on CRC by synergistically inhibiting the DNA damage repair pathway and activating the tumor cell apoptosis process without obvious toxicity. In addition, the Nir-Ir NPs could effectively reverse irinotecan-resistance by inhibiting the expression of multiple resistance protein-1 (MRP-1). Overall, our study underscores the distinctive advantages and potential of Nir-Ir NPs as a complementary strategy to chemotherapy by simultaneously overcoming the Ir resistance and improving the anti-tumor efficacy against CRC.