ABSTRACT Niclosamide (NIC) shows antitumor activity by inhibiting multiple signaling pathways, including signal transducer and activator of transcription 3, Wnt/β‐catenin, and NF‐κB. However, the poor aqueous solubility and bioavailability limit its potential in treating systemic diseases. To address this, we report here the synthesis of a pH‐responsive block copolymer PLLA‐ b ‐PDMAEMA‐Q based on poly(L‐lactide) (PLLA) and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) diblock copolymer. First, the PLLA block was prepared by ring‐opening polymerization (ROP) followed by the diblock, by atom transfer radical polymerization (ATRP) to prepare PLLA‐ b ‐PDMAEMA. Three different block copolymer compositions were synthesized by varying the molecular weight ratio of PLLA to PDMAEMA at 1:2, 1:1, and 1:0.5. PLLA‐ b ‐PDMAEMA was then quaternized by reaction with bromoacetic acid to generate PLLA‐ b ‐PDMAEMA‐Q. In aqueous solution, these copolymers were found to self‐assemble into micelles with a hydrodynamic diameter of 79–107 nm. PLLA‐ b ‐PDMAEMA‐Q was converted to its polyzwitterionic analogue PLLA‐ b ‐PDMAEMA‐ZIP in PBS buffer (pH 7.4) and used for encapsulation of NIC. The NIC‐loaded PLLA‐ b ‐PDMAEMA‐ZIP (ZIP‐NIC) showed a spherical morphology with a hydrodynamic diameter of 230 ± 15.81 nm and significant uptake in HCT116 cells. ZIP‐NIC exhibited similar anti‐cancer efficacy to free NIC in the HCT116 cell line. Our results suggest that polyzwitterionic nanoparticles constitute a promising class of materials to deliver antitumor drugs and warrant further investigation.
Pandey et al. (Thu,) studied this question.