DOX-loaded pH-sensitive mesoporous silica nanoparticles coated with PDA and PEG induce pro-death autophagy in breast cancer

The development of multifunctional nano drug delivery carriers has been one of the most effective and prevailing approaches to overcome drug non-selectivity, low cell uptake efficiency and various side effects of traditional chemotherapy drugs. Herein, we report a novel doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and polyethylene glycol (PEG) (MSNs-DOX@PDA-PEG) for the treatment of breast cancer. In this system, PDA functions as a pH-sensitive gatekeeper to control the release of DOX from MSNs in response to pH-stimulus and PEG was further grafted on the surface of PDA to increase the stability and biocompatibility under physiological conditions. The in vitro release results suggested that MSNs-DOX@PDA-PEG exhibits a high sensitivity to low pH. A cellular uptake assay showed a high cellular uptake efficiency of MSNs-DOX@PDA-PEG compared to free DOX. Furthermore, MSNs-DOX@PDA-PEG also demonstrated an improved anti-cancer efficacy compared to free DOX both in vivo and vitro breast cancer experiments. Mechanistic studies revealed that MSNs-DOX@PDA-PEG causes a stronger pro-death autophagy compared to free DOX via inhibition of the AKT-mTOR-p70S6K signaling pathway. Taken in concert, our results suggest that the novel material MSNs-DOX@PDA-PEG may represent a promising nanoformulation for breast cancer treatment.