Phenyl boronic acid -PEG-stearic acid biomaterial-based and sialic acid targeted nanomicelles for colon cancer treatment

This study aims to develop and evaluate a sialic acid receptor-targeting biomaterial for an effective delivery of usnic acid (UA). The novel biomaterial system is composed of three different parts; (1) stearic acid (SA) a hydrophobic core for encapsulation of UA, (2) PEG spacer to make conjugate amphiphilic, and (3) at the periphery phenylboronic acid (PBA) for cancer cell targeting. The synthesized PBA-PEG-SA biomaterial was characterized by FTIR NMR, and MALDI-TOF analysis. An average molecular weight of PBA-PEG-SA was about 3896 Da. The PBA-PEG-SA biomaterial was self-assembled into the nanomicelles with a 460 μg/mL CMC value. The UA-loaded PBA-PEG-SA nanomicelles (UPNM) were analysed by DLS, TEM, FTIR NMR, DSC and XRD techniques. The average particle size of UPNM was about 160 nm and its spherical nature was confirmed by TEM analysis. The synthesized biomaterial provided a pH-sensitive and controlled release of encapsulated UA with < 10% release at gastric pH 1.2 while > 90% release at intestinal pH 6.8. In vitro cytotoxicity potential of developed UPNM was investigated against HCT116 human colon cancer cells. The in vitro results proved that the synthesized PBA-PEG-SA biomaterial had good biocompatibility and PBA decorated nanomicelles could be successfully uptaken by HCT116 cancer cells. The observed IC50 value for UPNM (5.37 ± 0.78 μg/mL) was significantly lower (p < 0.01) than pure UA (8.57 ± 0.26 μg/mL) or non-targeted UA-loaded nanomicelles (8.36 ± 0.63 μg/mL). Further, the targeted nanomicelles showed higher apoptosis and greater control over the colony formation ability of HCT116 cells than pure drug or non-targeted UA-loaded nanomicelles.