Zwitterionic Polypeptide-Based Nanodrug Augments pH-Triggered Tumor Targeting via Prolonging Circulation Time and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Chemotherapeutic drugs cause significant side effects on healthy organs.
• There is a need for novel drug delivery systems to improve antitumor efficacy and reduce toxicity.

Purpose of the Study:

• To develop a novel albumin-mimicking nanodrug for enhanced pH-triggered tumor targeting.
• To improve circulation time and cellular internalization of chemotherapeutic agents.
• To augment antitumor efficacy while minimizing side effects.

Main Methods:

• A zwitterionic poly(glutamatyl lysine-co-cysteine) peptide scaffold was used to create the nanodrug.
• Cellular internalization was compared between the nanodrug, Doxil, and free doxorubicin (Dox) at pH 6.7.
• Circulation time and biodistribution in tumor, liver, and kidney were evaluated.
• Antitumor efficacy and impact on mouse body weight were assessed.

Main Results:

• The nanodrug exhibited faster cellular internalization in MCF-7 cells at pH 6.7 compared to Doxil and free Dox.
• Nanodrug internalization was significantly lower in RAW-264.7 cells, indicating tumor specificity.
• The nanodrug demonstrated a prolonged circulation time, comparable to Doxil.
• Higher accumulation of the nanodrug was observed in tumors versus liver and kidney.
• The nanodrug achieved a significantly higher tumor inhibition rate (93.2%) than Doxil (54.2%) with improved mouse body weight.

Conclusions:

• The albumin-mimicking nanodrug effectively enhances pH-triggered tumor targeting through prolonged circulation and accelerated cellular internalization.
• This nanodrug strategy significantly augments antitumor efficacy and reduces systemic toxicity.
• This approach holds promise for rejuvenating traditional chemotherapeutic treatments.