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Niclosamide Encapsulated pH-Responsive Polyzwitterionic Block Copolymers for Cancer Therapy.

Monu Pandey1,2, Debojit Chakraborty3, Shubhra Goel3

  • 1Centre for Biomedical Engineering, Indian Institute of Technology Delhi, India.

Macromolecular Bioscience
|January 20, 2026
PubMed
Summary
This summary is machine-generated.

This study developed pH-responsive polyzwitterionic nanoparticles to improve the delivery of niclosamide (NIC), an anticancer drug. The novel nanoparticles effectively delivered NIC to cancer cells, showing promising anti-cancer efficacy and potential for systemic disease treatment.

Keywords:
block copolymerscancer therapypH‐responsivezwitterionic micelles

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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.