Wet Nanoscale Imaging and Testing of Polymersomes

Polymeric vesicles, a.k.a. “polymersomes”, are enclosed membranes formed by the self-assembly of amphiphilic block copolymers in water.[1] In recent years polymersomes have attracted much attention due to their unique features, such as improved mechanical properties, high stability, and long circulation half-lives in the body compared to liposomes, as well as their ability to incorporate both hydrophilic compounds in the aqueous core and hydrophobic compounds in the membrane.[1a] Furthermore, amphiphilic block copolymers can be designed to be noncytotoxic, efficiently internalized by cells, etc.[2] Polymersomes can be decorated with proteins and/or antibodies, either by chemically attaching the active moieties to the hydrophilic brushes[3] or by inserting membrane proteins across the hydrophobic membrane.[4] Recently, fine control over polymersome surface topology and its consequences on cell internalization kinetics has been demonstrated by the authors.[5] Thus the ability to examine the surface properties of polymersomes, as well as other water-borne nanoparticles, in situ on the nanoscale is becoming increasingly important in several fields. Imaging of wet nanoparticles is normally performed by transmission or scanning electron microscopy (EM). However, the high vacuum conditions necessary for such imaging require either dried or frozen (e.g., cryogenic EM) samples, potentially causing artefacts. Wet imaging can be performed by optical microscopy and recently the problem of diffraction-limited spatial resolution has been overcome by new fluorescence-based microscopy, such as scanning near-field optical microscopy (SNOM), photo-activated localization microscopy (PALM), stimulated emission depletion microscopy (STED), and structured illumination microscopy (SIM).[6] Atomic force microscopy (AFM) is another valuable analytical tool that has been used for both imaging and also for assessing mechanical, electrical, and surface properties.[7]