Systemically Applicable Glutamine-Functionalized Polymer Exerting Multivalent Interaction with Tumors Overexpressing...

Area of Science:

• Biomaterials Science
• Cancer Biology
• Drug Delivery

Background:

• The amino acid transporter ASCT2 (alanine, serine, cysteine transporter 2) is frequently overexpressed in various cancer types.
• Targeting ASCT2 presents a promising strategy for cancer diagnosis and therapeutic interventions.

Purpose of the Study:

• To design and evaluate glutamine-modified polymers for ASCT2-mediated tumor targeting.
• To investigate the influence of polymer architecture and molecular weight on tumor accumulation and cellular uptake.

Main Methods:

• Synthesis of poly(l-lysine) (PLys) homopolymers and PEG-PLys block copolymers modified with glutamine (Gln).
• Assessment of cellular uptake via multivalent interactions with ASCT2.
• Evaluation of tumor targeting and accumulation following systemic administration in vivo.

Main Results:

• Increased degree of polymerization in PLys(Gln) homopolymers enhanced cellular uptake through multivalent ASCT2 interactions.
• PEG-PLys(Gln) block copolymers demonstrated controllable blood circulation and tumor accumulation by adjusting polyethylene glycol (PEG) molecular weight.
• Successful tumor targeting was achieved through ASCT2/PLys(Gln) molecular recognition.

Conclusions:

• Glutamine-modified polymers effectively target ASCT2-overexpressing cancer cells.
• The developed polymers show potential for systemic tumor diagnosis and therapy.
• Molecular recognition strategies offer a viable pathway for targeted cancer treatment.