Publications

A bottom-up approach to fabricating monodisperse, two-component polymersomes that possess phase-separated ("patchy") chemical topology is presented. This approach is compared with already-existing top-down preparation methods for patchy polymer vesicles, such as film rehydration. These findings demonstrate a bottom-up, solvent-switch self-assembly approach that produces a high yield of nanoparticles of the target size, morphology, and surface topology for drug delivery applications, in this case patchy polymersomes of a diameter of ≈50 nm. In addition, an image processing algorithm to automatically calculate polymersome size distributions from transmission electron microscope images based on a series of pre-processing steps, image segmentation, and round object identification is presented.© 2023 Wiley-VCH GmbH.

JTD Keywords: assemblies, copolymers, evolution, membranes, micelles, ph, phase separation, polymersomes, rafts, self-assembly, size, vesicles, Cell biology, Drug delivery, Phase separation, Polymersomes, Self-assembly, Vesicles

Nanosized artificial antigen-presenting cells (aAPCs), synthetic immune cell mimics that aim to activate T cells ex or in vivo, offer an effective alternative to cellular immunotherapies. However, comprehensive studies that delineate the effect of nano-aAPC topology, including nanoparticle morphology and ligand density, are lacking. Here, we systematically studied the topological effects of polymersome-based aAPCs on T cell activation. We employed an aAPC library created from biodegradable poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PDLLA) polymersomes with spherical or tubular shape and variable sizes, which were functionalized with αCD3 and αCD28 antibodies at controlled densities. Our results indicate that high ligand density leads to enhancement in T cell activation, which can be further augmented by employing polymersomes with larger size. At low ligand density, the effect of both polymersome shape and size was more pronounced, showing that large elongated polymersomes better activate T cells compared to their spherical or smaller counterparts. This study demonstrates the capacity of polymersomes as aAPCs and highlights the role of topology for their rational design.

JTD Keywords: antibody density, artificial antigen-presenting cells, biodegradable polymersomes, design, expansion, immunotherapy, nano-immunotherapy, nanoparticle morphology, t cell activation, Biodegradable polymersomes, Nanoparticle morphology, Synthetic dendritic cells

The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self-assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i-combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions. Using a range of microscopies and molecular simulations, the self-assembly of a library of combs in water is screened. It is discovered that the hydrophobic tails form the membrane's core and force the backbone into a rod conformation with nematic-like ordering confined to the interface with water. This particular organization resulted in membranes that combine the stability of classic polymersomes with the biomimetic thickness, flexibility, and lateral mobility of liposomes. Such unparalleled matching of biophysical properties and the ability to locally reconfigure the molecular topology of its constituents enable the harboring of functional components of natural membranes and fusion with living bacteria to “hijack” their periphery. This provides an almost inexhaustible palette to design the chemical and biological makeup of the i-combisomes membrane resulting in a powerful platform for fundamental studies and technological applications.

JTD Keywords: amphiphilic comb polymers, bottom-up synthetic biology, hybrid vesicles, polyelectrolyte-surfactant complexes, polymersomes, synthetic biomembranes, Amphiphilic comb polymers, Biomimetics, Bottom-up synthetic biology, Hybrid vesicles, Hydrophobic and hydrophilic interactions, Liposomes, Polyelectrolyte-surfactant complexes, Polymers, Polymersomes, Synthetic biomembranes, Vesicle fusion, Water

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JTD Keywords: cancer, cells, cellular basis, delivery, encapsulation, in-vitro, inflammation, macrophage, methotrexate, pathogenesis, polymersome, polymersomes, synoviocyte, Arthritis, Rheumatoid-arthritis

Glucocorticoid (GC) drugs are the cornerstone therapy used in the treatment of inflammatory diseases. Here, we report pH responsive poly(2-methacryloyloxyethyl phosphorylcholine)–poly(2-(diisopropylamino)ethyl methacrylate) (PMPC–PDPA) polymersomes as a suitable nanoscopic carrier to precisely and controllably deliver GCs within inflamed target cells. The in vitro cellular studies revealed that polymersomes ensure the stability, selectivity and bioavailability of the loaded drug within macrophages. At molecular level, we tested key inflammation-related markers, such as the nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and interleukin-6. With this, we demonstrated that pH responsive polymersomes are able to enhance the anti-inflammatory effect of loaded GC drug. Overall, we prove the potential of PMPC–PDPA polymersomes to efficiently promote the inflammation shutdown, while reducing the well-known therapeutic limitations in GC-based therapy.

JTD Keywords: Inflammation, Macrophages, Glucocorticoid, Polymersomes