Figure 2. Vesicle sizes achieved by different kinds of film rehydration, controlled and uncontrolled and also using electroformation. 62 Electroformation itself is shown on the left where dome-like structures evolve with PEG−PDEA. 66 (Part (a) reproduced with permission from ref 62. Copyright (2009) Nature Publishing Group).Figure 3. Possible structures observed when using a pH guided assembly of poly((butyl)methacrylate)−poly(methacrylic acid) PBMA−PMA via 2 pathways of vesicle creation (VC1 and VC2) and the final creation of spheres (CS1 and CS2). 68 (Reproduced with permission from ref 68. Copyright (2009) Royal Society of Chemistry).
Polymeric vesicles or polymersomes are one of the supramolecular entities at the leading edge of synthetic biology. These small compartments have shown to be feasible candidates as nanoreactors, especially for enzymatic reactions. Once cross-linked and equipped with a pH sensitive material, the reaction can be switched off (pH 8) and on (pH 6) in accordance with the increased permeability of the polymersome membranes under acidic conditions. Thus cross-linked and pH sensitive polymersomes provide a basis for pH controlled enzymatic reactions where no integrated transmembrane protein is needed for regulating the uptake and release of educts and products in the polymersome lumen. This pH-tunable working tool was further used to investigate their use in sequential enzymatic reactions (glucose oxidase and myoglobin) where enzymes are loaded in one common polymersome or in two different polymersomes. Crossing membranes and overcoming the space distance between polymersomes were shown successfully, meaning that educts and products can be exchanged between enzyme compartments for successful enzymatic cascade reactions. Moreover the stabilizing effect of polymersomes is also observable by single enzymatic reactions as well as a sequence. This study is directed to establish robust and controllable polymersome nanoreactors for enzymatic reactions, describing a switch between an off (pH 8) and on (pH 6) state of polymersome membrane permeability with no transmembrane protein needed for transmembrane exchange.
Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions.
In recent years, scientists have created artificial microscopic and nanoscopic self-propelling particles, often referred to as nano-or microswimmers, capable of mimicking biological locomotion and taxis. This active diffusion enables the engineering of complex operations that so far have not been possible at the micro-and nanoscale. One of the most promising tasks is the ability to engineer nanocarriers that can autonomously navigate within tissues and organs, accessing nearly every site of the human body guided by endogenous chemical gradients. We report a fully synthetic, organic, nanoscopic system that exhibits attractive chemotaxis driven by enzymatic conversion of glucose. We achieve this by encapsulating glucose oxidase alone or in combination with catalase into nanoscopic and biocompatible asymmetric polymer vesicles (known as polymersomes). We show that these vesicles self-propel in response to an external gradient of glucose by inducing a slip velocity on their surface, which makes them move in an extremely sensitive way toward higher-concentration regions. We finally demonstrate that the chemotactic behavior of these nanoswimmers, in combination with LRP-1 (low-density lipoprotein receptor-related protein 1) targeting, enables a fourfold increase in penetration to the brain compared to nonchemotactic systems.
Polymersomes are versatile nanoscale vesicles that can be used for
cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive
polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor
lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR)
motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering
extravasation and tumor penetration of the peptide. iRGD functionalization
increases tumor selectivity and therapeutic efficacy of systemic drug-loaded
nanoparticles in many tumor models. Here we studied whether intraperitoneally
administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the
treatment of peritoneal carcinomatosis. First, we demonstrated that the
pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR
peptide) or iRGD internalize in the cells that express NRP-1, and that
internalized polymersomes release their cargo inside the cytosol. CendR-targeted
polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells
than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric
(MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and
iRGD-polymersomes showed higher tumor-selective accumulation and penetration
than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel
showed improved efficacy in peritoneal tumor growth inhibition and in
suppression of local dissemination compared to the pristine
paclitaxel-polymersomes or Abraxane.
Our study demonstrates that iRGD-functionalization improves efficacy of
paclitaxel-polymersomes for intraperitoneal treatment of peritoneal
carcinomatosis.
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