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Covalently assembled dual-functional triple-helix lentinan-Au for cervical cancer therapy
Xinjian Lu1, Lei Feng1, Li Zhang1
1State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, 330047, China.
Abstract:
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.
Insights
A novel lentinan-gold cluster complex (LNT-Au) shows promise for cervical cancer therapy. This dual-functional agent enhances tumor cell apoptosis and inhibits growth by combining polysaccharide benefits with gold cluster activity.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Cervical cancer necessitates advanced therapeutic strategies.
- Polysaccharides offer anti-cancer potential but have limited efficacy.
- Gold clusters possess peroxidase-like activity but suffer from rapid clearance.
Purpose of the Study:
- To develop a dual-functional lentinan-gold cluster complex (LNT-Au) for enhanced cervical cancer therapy.
- To leverage the biocompatibility and peroxidase-like activity of gold clusters conjugated with lentinan.
- To improve the tumor-targeting and therapeutic efficacy of anti-cancer agents.
Main Methods:
- Covalent conjugation of lentinan (LNT) with glutathione-capped gold clusters (Au-GSH) to form LNT-Au.
- Evaluation of LNT-Au biocompatibility and peroxidase-like (POD-like) activity.
- In vivo studies in tumor-bearing nude mice to assess therapeutic outcomes.
Main Results:
- LNT-Au demonstrated excellent biocompatibility and enhanced POD-like activity.
- The complex promoted pro-apoptotic gene expression (Bax) and suppressed anti-apoptotic genes (Bcl-2), activating Caspase-3.
- Elevated reactive oxygen species (ROS) levels were observed, contributing to tumor cell apoptosis and significant tumor growth inhibition.
Conclusions:
- LNT-Au effectively targets and treats cervical cancer by synergizing lentinan's anti-tumor effects with gold clusters' ROS-generating capability.
- The developed complex offers a promising therapeutic strategy for cervical cancer, enhancing tumor cell apoptosis and growth inhibition.
- This work provides a foundation for advancing polysaccharide-based multi-functional combination therapies in oncology.
