Cytotoxicity of PMMA-Based Nanoparticles Synthesized Adopting SDS and Tween 80 Claudio Colombo, 1 Monica Lupi, 2 Paolo Ubezio, 2 Davide Moscatelli * 1 Summary: in this work the cytotoxicity of PMMA-based nanoparticles against mouse mammary cancer cells (4T1) has been investigated. NPs have been synthesized using either monomer starved semi-batch emulsion polymerization (MSSEP) or standard batch emulsion polymerization (BEP) processes adopting potassium persulfate (KPS) as initiator and two different emulsifiers: sodium dodecyl sulfate (SDS) and Tween 80. The toxicity of NPs produced using SDS has been confirmed in in vitro experiments while it has been found that NPs stabilized with Tween 80 show a good biocompatibility. Moreover, the absence of toxicity of NPs in which the SDS is substituted with Tween 80 adopting ion exchange resins (IER) has been proved. Finally the biocompatibility of the sulfate chain end groups coming from the adopted initiator has been assessed. Keywords: biocompatibility; nanoparticles; PMMA; SDS; surfactants Introduction Polymeric materials have been studied extensively in the last years for their biomedical applications ranging from resorbable sutures to scaffolds and from tissue engineering to vectors for drug delivery applications. Therapeutics nano- particles (NPs) have many potential advan- tages such as the ability to target specific tissues or cells and the possibility to deliver drugs through biological barriers. [1] Among all the possible synthetic routes, the most common processes adopted to obtain poly- meric NPs are the nanoprecipitation, [2] the solvent evaporation, [3] and the emulsion polymerization, which has the advantage of being an organic solvent-free process. Emulsion polymerization requires the use of a surfactant in order to stabilize the NPs that can cause serious toxicity issues. [4] In particular, sodium dodecyl sulfate (SDS) which is one of the most used surfactants, was demonstrated to be toxic to cells because of its capacity to bind to various bioactive macromolecules such as proteins, peptides and DNA or to insert into various cell fragments (i.e. phospholipid mem- branes) causing misfunction. [5,6] On the other hand, the use of SDS in both monomer starved semi-batch emulsion polymerization (MSSEP), in which the monomer is slowly fed in the reactor in order to ensure starved condition, [7] and batch emulsion polymerization (BEP) pro- cesses, allows obtaining well defined mono- dispersed NPs tunable in terms of dimension and z potential. [8] Recently, the possibility to synthesize tunable fluorescent PMMA- based NPs for imaging applications has been reported in literature. [9] In the latter publication Dossi et al. synthesized poly- mer NPs using KPS as initiator, SDS and Tween 80 as surfactants and adopting both MSSEP and BEP processes. In this work the toxicity of PMMA-based NPs has been investigated starting from the results reported by Dossi et al.. In particular the cytotoxicity of the NPs obtained adopting SDS and Tween 80 has been evaluated along with the effects of the SDS substitu- tion with Tween 80 using ion exchange resins (IER) as reported in Scheme 1. The Macromol. Symp. 2013, 324, 134–139 DOI: 10.1002/masy.201200078 134 1 Department of Chemistry, Materials and Chemical Engineering ‘‘Giulio Natta’’, Politecnico di Milano, Via Luigi Mancinelli 7 -20131 Milano, Italy E-mail: davide.moscatelli@polimi.it 2 Department of Oncology, Mario Negri Institute for Pharmacological Research, Via La Masa 19–20156 Milano, Italy Copyright ß 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com