Functionalizing Sgc8-Paclitaxel Conjugates with F-Base Modifications: Targeted Drug Delivery with Optimized Cardiac...

Area of Science:

• Biochemistry
• Nanotechnology
• Cardiology

Background:

• Chemotherapy-induced cardiotoxicity is a significant challenge in cancer treatment.
• Targeted drug delivery systems aim to improve efficacy and reduce side effects.

Purpose of the Study:

• To evaluate the cardiotoxicity and efficacy of F-base-modified aptamer-paclitaxel conjugates (Sgc8-F23-PTX) as a targeted drug delivery system.
• To compare Sgc8-F23-PTX with nanoparticle albumin-bound paclitaxel (Nab-PTX) regarding cardiac safety.

Main Methods:

• Synthesis of F-base-functionalized Sgc8 aptamer and conjugation with paclitaxel (PTX).
• Assessment of cardiac function using echocardiography in a myocardial infarction model.
• Analysis of cardiomyocyte apoptosis and autophagy.
• Evaluation of ion channel effects (hERG, hNav1.5, hCav1.2).

Main Results:

• Sgc8-F23-PTX demonstrated prolonged circulation time and enhanced anticancer efficacy.
• No cardiotoxicity, pathological changes, or increased apoptosis were observed in non-infarcted cardiac regions.
• Sgc8-F23-PTX did not induce significant autophagy or apoptosis in cardiomyocytes, unlike Nab-PTX.
• No inhibitory effects on key cardiac ion channels were detected.

Conclusions:

• F-base-modified Sgc8 aptamers represent a safe and effective platform for targeted anticancer drug delivery.
• This approach shows potential for reducing chemotherapy-induced cardiotoxicity in clinical applications.
• Further research is needed for clinical translation and exploring other drug carriers.