Covalently assembled dual-functional triple-helix lentinan-Au for cervical cancer therapy
The aggressive nature of cervical cancer urgently calls for effective therapeutic scenarios. Polysaccharides show great potential for anti-cervical cancer therapies, while their efficacy is limited. Gold clusters exhibit strong peroxidase-like (POD-like) activity that promotes tumor cell apoptosis, but rapid renal clearance hinders their potential for cancer therapy. Herein, lentinan (LNT) was covalently conjugated with glutathione-capped gold clusters (Au-GSH), forming a dual-functional triple-helix complex (LNT-Au) with excellent biocompatibility and POD-like activity. Owing to the mild reaction conditions and the relatively large molecular weight, LNT-Au preserved the inherent anti-tumor effects of LNT and enhanced the delivery of gold clusters to the tumor site. Following intravenous injection into tumor-bearing nude mice, the polysaccharide component promoted pro-apoptosis Bax expression, suppressed anti-apoptosis Bcl-2 expression, and subsequently activated Caspase-3. These effects were further amplified by elevated levels of reactive oxygen species (ROS) generated through the POD-like catalytic activity of the conjugated gold clusters. These features contributed to a satisfactory therapeutic outcome toward cervical cancer, as evidenced by enhanced tumor cell apoptosis and significant inhibition of tumor growth. Overall, LNT-Au developed here provides a promising and effective therapeutic strategy for cervical cancer, laying a strong foundation for the advancement of polysaccharide-based multi-functional combination therapies.
Journal
Carbohydrate PolymersAuthors
Funding
National Natural Science Foundation of China Grant 32372322State Key Laboratory of Food Science and Resources FundingNanchang University FundingJiangxi Provincial Natural Science Foundation Grant 20224ACB215009Jiangxi Provincial Natural Science Foundation Grant 20232ACB205024State Key Laboratory of Food Science & Resources Grant SKLF-KF-202214