Synthetic drug-carrying nanomaterials offer great potential as targeted cellular delivery vehicles. Typically, their size, morphology, surface chemistry and stability are optimized in order to control their effect on drug release kinetics, cellular uptake pathways, efficiency and site of action. However, methods to track the carriers and their cargo independently at the micro- and nanoscale have been severely underutilized preventing the correlation between structure and function.<br/>We found that by directly polymerizing an oxaliplatin analogue containing a norbornyl moiety amenable to polymerization via ring opening metathesis polymerization (ROMP) we could generate amphiphiles, which can self-assemble into well-defined NPs in a reproducible manner. Our results demonstrate that the covalently loaded NPs are equipotent with free oxaliplatin and are taken up intact via endocytic pathways before release of the cytotoxic cargo. This was confirmed by super resolution fluorescence structured illumination microscopy (SIM) and nanoscale secondary ion mass spectrometry (NanoSIMS).<br/>We anticipate that this type of multimodal cellular tracking of NP and drug could help to bridge the knowledge gap between particle structure and performance for the vast array of currently generalizable systems in the literature.

Cellular delivery of platinum(II)-loaded nanoparticles revealed with combined optical and isotopic nanoscopy

251st National Meeting (2016)

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