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

Abstract

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 μg/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.