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Nanosystems often require different surface coatings to improve their biocompatibility, circulating time, the intracellular uptake and reduce toxic side effects. A pre-understanding and a simple controlling of the surface coatings' interactions with biological systems are of vital importance. Herein, we successfully modified model nanoparticles (NPs) with three surface modifiers: bovine serum albumin (BSA), poly-L-lysine (PLL) and polyethylene glycol (PEG) simply and uniformly via polydopamine (pD). Following, the serum stability, drug release profile, pharmacokinetics, in vivo biodistribution and interactions with tumor cells of these modified nanoparticles were systematically evaluated for further applications. According to the in vitro and in vivo results, BSA coated NPs could inhibit the plasma proteins' adsorption thus prolong their circulation time to some extent. In addition, the BSA shell showed good biocompatibility, non-toxicity and a delayed drug release. Interestingly, PLL coated NPs exhibited higher and pH-dependent intracellular uptake and antitumor activity in an acidic tumor micro environment. Nonetheless, the PLL coating did not exhibit particularly high toxicity due to its low positive charge density. PEG coated NPs displayed good pharmacokinetic profiles as expected. In the light of the successful application of the above pD–surface modifier compound shells (pD–BSA, pD–PLL, pD–PEG), diverse particles can be modified to selectively optimize their nature and achieve the goal such as improved pharmacokinetic profiles, enhanced cellular internalization ability and lower toxicity. This strategy that can selectively alter the biological fate of NPs simply by tunable coatings provides great potential for controllable drug delivery systems for cancer and other therapeutic or diagnostic applications.

Simple and tunable surface coatings via polydopamine for modulating pharmacokinetics, cell uptake and biodistribution of polymeric nanoparticles