CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis...

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Cancer Research

Background:

• Tumor neovascularization drives cancer progression, necessitating antiangiogenic therapies.
• Current antiangiogenesis treatments alone are insufficient for effective tumor therapy.
• Polysaccharides offer potential as drug carriers for modified drug delivery.

Purpose of the Study:

• To develop a novel redox and acid-sensitive nanodrug (CCEA) for enhanced tumor treatment.
• To evaluate the antiangiogenic and antitumor properties of CCEA in vitro and in vivo.
• To elucidate the mechanism of CCEA-induced tumor cell apoptosis.

Main Methods:

• Synthesis of a nanodrug (CCEA) comprising cisplatin (CDDP), chondroitin sulfate (CS), and endostatin2-alft1 (EA).
• In vitro assessment of CCEA's redox/acid sensitivity, hemocompatibility, tumor targeting (CD44-mediated endocytosis), antiangiogenesis, and antitumor effects.
• In vivo evaluation of CCEA's antitumor activity and toxicity in B16 xenograft mice, including apoptosis pathway analysis.

Main Results:

• CCEA demonstrated redox and acid responsiveness, excellent hemocompatibility (hemolysis < 5%), and CD44-mediated tumor targeting.
• In vitro studies showed strong antiangiogenesis and antitumor characteristics.
• In vivo studies revealed significant antitumor activity with low toxicity in B16 xenograft mice, inducing apoptosis via Bax/Bcl-2 modulation and caspase activation.

Conclusions:

• The developed CCEA nanodrug exhibits promising antiangiogenic and antitumor efficacy.
• CCEA effectively induces tumor cell apoptosis through intrinsic and extrinsic pathways.
• This study provides a foundation for developing advanced nanodrugs for cancer therapy.