Apoferritin-Encapsulated Jerantinine A for Transferrin Receptor Targeting and Enhanced Selectivity in Breast Cancer...

Area of Science:

• Biochemistry
• Nanotechnology
• Oncology

Background:

• Jerantinine A (JAa), an Aspidosperma alkaloid derivative, exhibits anti-tumor properties by targeting microtubule dynamics.
• Breast cancer cells often overexpress transferrin receptor 1 (TfR1), a potential target for drug delivery.
• Apoferritin (AFt) is a biocompatible protein cage that can be engineered for drug encapsulation and targeted delivery.

Purpose of the Study:

• To develop an AFt-based drug delivery vehicle for JAa to enhance tumor targeting and reduce systemic toxicity.
• To investigate the efficacy of AFt-encapsulated JAa (AFt-JAa) in TfR1-expressing breast cancer cells.
• To evaluate the anti-cancer effects of AFt-JAa compared to naked JAa.

Main Methods:

• JAa was encapsulated into AFt via pH-mediated reassembly, with approximately 120 JAa molecules per AFt particle.
• TfR1 expression was confirmed in cancer cell lines using Western blot and flow cytometry.
• Cellular uptake, intracellular drug levels, cytotoxicity, cell cycle progression, apoptosis, and protein expression were assessed.

Main Results:

• AFt demonstrated enhanced internalization in SKBR3 and MDA-MB-231 breast cancer cells compared to fibroblasts.
• AFt-JAa delivered significantly higher intracellular JAa levels to cancer cells than naked JAa.
• AFt-JAa exhibited enhanced growth inhibition (2.5-14-fold increase in potency), reduced clonal survival, increased G2/M arrest, and augmented apoptosis compared to naked JAa.

Conclusions:

• AFt serves as an effective and biocompatible vehicle for targeted delivery of JAa to TfR1-expressing breast cancer cells.
• AFt-JAa significantly enhances the anti-tumor activity of JAa while potentially minimizing systemic toxicity.
• This targeted nanodelivery system holds promise for improved therapeutic outcomes in TfR1-positive tumors.