Molecular bottlebrush with pH-responsive cleavable bonds as a unimolecular vehicle for anticancer drug delivery

Drug delivery systems with targeted and smart properties have emerged as an efficient strategy to overcome the challenges of cancer chemotherapy such as toxic side effects and the development of multidrug resistance. In this study, a biocompatible bottlebrush polymer poly((3-(2-bromo-2-methylpropionate)propyldimethylsilyloxy)ethyl methacrylate)-graft-poly(2-methacryloyloxyethyl phosphorylcholine) P(BIBS-EMA)-g-PMPC with pH-responsive silanol cleavable bond was designed and developed for delivery of doxorubicin. A549 cell line of human lung carcinoma was tested. The synthesized bottlebrush polymer was analyzed and characterized via Fourier transform infrared spectroscopy, FTIR, nuclear magnetic resonance spectroscopy, ¹H NMR, gel permeation chromatography, GPC, dynamic laser light scattering, DLS, and static laser light scattering, SLS, techniques. The cleavage process was also precisely studied to confirm the pH-responsiveness of such bottlebrush polymers. In vitro loading and release studies of doxorubicin as a model drug were examined and the results showed a pH-dependent release manner with a twice higher release rate under cancerous tissue conditions compared to standard physiological conditions. MTT cytotoxicity assay was also performed to prove the biocompatibility of the designed polymeric platform on healthy human cells. Due to the presence of bio-inspired poly(2-methacryloyloxyethyl phosphorylcholine) side chains in the prepared bottlebrush polymer, the formed polymer-drug complex could also exhibit effective internalization into tumor cells. These facts further support the potential use of this carrier in drug delivery applications and for further in vivo studies.