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A combined "RAFT" and "Graft From" polymerization strategy for surface modification of mesoporous silica nanoparticles: towards enhanced tumor accumulation and cancer therapy efficacy.

A novel modification route integrating the copolymers of positive charged quaternary amines and polyethylene glycol (PEG) units using a combination of reversible addition-fragmentation chain-transfer polymerization (RAFT) and "Graft From" strategy, has been proposed and developed, for the first time, to decorate the surface of mesoporous silica nanoparticles (MSNs). These MSNs are shown to have a greatly reduced hydrodynamic particle size in physiological solution. It is demonstrated that such an efficient copolymer surface modification strategy, resulting in PEG coating with high positive zeta potential, can achieve a nearly 2-fold enhanced permeability and retention (EPR) effect, and longer blood half-life compared to coating with PEG only. Besides, the in vivo results demonstrated that this surface modification strategy could lead to a higher efficacy of doxorubicin (DOX) drug delivery and greater suppression of side effects compared to the free drug. Based on this novel strategy of combining "RAFT" and "Graft From" polymerization, it is anticipated that this efficient modification of tumor-specific targeting of MSNs can be widely used in future nanomedicine research.