Synthesis of doxorubicin-loaded PBMA-b-POEGMA micelles and assessment of its anticancer activity against breast cancer cells (4T1)

Doxorubicin (DOX) is a chemotherapy drug that possesses many side effects. This study aimed to synthesize PBMA-b-POEGMA [poly (butyl methacrylate)-b-poly (oligo ethylene glycol methacrylate)] diblock copolymer as a nanocarrier for loading of DOX, promoting anticancer efficacy of the drug, and decreasing its side effects. Hence, PBMA-b-POEGMA diblock copolymer was first synthesized by the RAFT method and then DOX encapsulated into the micellar nanocarrier. Self-assembly behavior of copolymers and physicochemical/biological properties of nanocarriers were assessed. DLS and TEM images showed nanocarriers possessed spherical-uniform structure with the mean size and polydispersity of 27 +/- 1.34 nm and 0.13 +/- 0.21 for blank-micelles as well as, 45 +/- 2.32 nm and 0.18 +/- 0.18 for DOX-loaded micelles, respectively. Synthesized micelles also provided high drug encapsulation efficiency (>80%) with a drug loading content of 4.53%. Moreover, the maximum released amount of drug was reported at 69%, with the Korsmeyer-Peppas model, as a more suitable model to describe the release behavior of DOX from nanocarriers. Biologically, block copolymers were biocompatible against COS-7 and 4T1 cell lines, in addition, free-DOX showed higher cytotoxicity than DOX-loaded micelles. Furthermore, 0.5 mu g/mL concentration of drug-loaded micelle led to growth inhibition of more than 60% of cancerous cells, during 48 h, so that higher level of cellular uptake of drug and apoptosis in 4T1 cells was induced by drug-loaded micelles.

Automated summary

This study synthesized a nanocarrier for the chemotherapy drug doxorubicin (DOX) to enhance its anticancer efficacy while reducing side effects. The nanocarrier, made of PBMA-b-POEGMA diblock copolymer, demonstrated good physicochemical and biological properties. It efficiently encapsulated DOX and released the drug using the Korsmeyer-Peppas model. The DOX-loaded micelles showed high cellular uptake and induced apoptosis in cancer cells.