A dendritic polyamidoamine supramolecular system composed of pillar[5]arene and azobenzene for targeting drug-resistant colon cancer

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2021-12, Vol.9 (46), p.9594-965
• Main Authors: Liu, Hongyu, Yang, Jie, Yan, Xiangjie, Li, Chaoqi, Elsabahy, Mahmoud, Chen, Li, Yang, Ying-Wei, Gao, Hui
• Format: Article
• Language: English
• Subjects: Ammonium; Animals; Anti-Bacterial Agents; Antibacterial activity; Antibacterial agents; Anticancer properties; Antifungal Agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Azo compounds; Azo Compounds - chemistry; Azoreductase; Biocompatibility; Cancer therapies; Cations; Cell membranes; Cell Survival; Chemotherapy; Colon; Colon cancer; Colorectal carcinoma; Cytology; Drug Design; Drug resistance; Drug Resistance, Fungal; Drug Resistance, Neoplasm; Fusobacterium nucleatum - drug effects; HT29 Cells; Humans; Male; Mice; Mice, Nude; Models, Molecular; Molecular Structure; Nanoparticles; Nanoparticles - chemistry; Neoplasms, Experimental; Polyamines - chemistry; Quaternary Ammonium Compounds - chemistry; Side effects; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb02134f

Fusobacterium nucleatum caused drug-resistant around tumor sites often leads to the failure of chemotherapy during colorectal cancer (CRC) treatment. Multifunctional cationic quaternary ammonium materials have been widely used as broad-spectrum antibacterial agents in antibacterial and anticancer fields. Herein, we design a smart supramolecular quaternary ammonium nanoparticle, namely quaternary ammonium PAMAM-AZO@CP[5]A (Q-P-A@CP[5]A), consisting of azobenzene (AZO)-conjugated dendritic cationic quaternary ammonium polyamidoamine (PAMAM) as the core and carboxylatopillar[5]arene (CP[5]A)-based switch, for antibacterial and anti-CRC therapies. The quaternary ammonium-PAMAM-AZO (Q-P-A) core endows the supramolecular system with enhanced antibacterial and anticancer properties. -N + CH 3 groups on the surface of Q-P-A are accommodated in the CP[5]A cavity under normal conditions, which significantly improves the biocompatibility of Q-P-A@CP[5]A. Meanwhile, the CP[5]A host can be detached from -N + CH 3 groups under pathological conditions, achieving efficient antibacterial and antitumor therapies. Furthermore, azoreductase in the tumor site can break the -N&z.dbd;N- bonds of AZO in Q-P-A@CP[5]A, leading to the morphology recovery of supramolecular nanoparticles and CRC therapy through inducing cell membrane rupture. Both in vitro and in vivo experiments demonstrate that Q-P-A@CP[5]A possesses good biocompatibility, excellent antibacterial effect, and CRC treatment capability with negligible side effects. This supramolecular quaternary ammonium system provides an effective treatment method to overcome chemotherapy-resistant cancer caused by bacteria. A smart supramolecular quaternary ammonium nanoparticle, namely quaternary ammonium PAMAM-AZO@CP[5]A (Q-P-A@CP[5]A) was designed to treat drug-resistant colorectal cancer (CRC) caused by Fusobacterium nucleatum.