Niclosamide Encapsulated pH-Responsive Polyzwitterionic Block Copolymers for Cancer Therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Niclosamide (NIC) exhibits significant antitumor activity by targeting key signaling pathways like STAT3, Wnt/β-catenin, and NF-κB.
• The therapeutic potential of NIC is severely limited by its poor aqueous solubility and low bioavailability, hindering its use in systemic disease treatment.

Purpose of the Study:

• To synthesize novel pH-responsive block copolymers for enhanced delivery of niclosamide (NIC).
• To develop polyzwitterionic nanoparticles for improved bioavailability and targeted delivery of anticancer agents.

Main Methods:

• Synthesis of a pH-responsive block copolymer, poly(L-lactide)-block-poly(2-(dimethylamino)ethyl methacrylate) (PLLA-b-PDMAEMA), via ring-opening polymerization and atom transfer radical polymerization.
• Quaternization of PLLA-b-PDMAEMA to yield PLLA-b-PDMAEMA-Q, followed by conversion to a polyzwitterionic analogue (PLLA-b-PDMAEMA-ZIP) in PBS buffer.
• Encapsulation of NIC into PLLA-b-PDMAEMA-ZIP nanoparticles (ZIP-NIC) and evaluation of their morphology, size, cellular uptake in HCT116 cells, and in vitro anti-cancer efficacy.

Main Results:

• The synthesized PLLA-b-PDMAEMA-Q copolymers self-assembled into micelles (79-107 nm) in aqueous solution.
• NIC-loaded polyzwitterionic nanoparticles (ZIP-NIC) exhibited a spherical morphology (230 ± 15.81 nm) and demonstrated significant uptake in HCT116 cancer cells.
• ZIP-NIC showed comparable anti-cancer efficacy to free NIC in the HCT116 cell line, indicating successful drug delivery.

Conclusions:

• Polyzwitterionic nanoparticles represent a promising platform for the effective delivery of poorly soluble anticancer drugs like niclosamide.
• The developed nanoparticle system demonstrates potential for overcoming bioavailability challenges and improving the therapeutic outcomes of systemic cancer treatments.