Morphology Under Control: Engineering Biodegradable Stomatocytes

Abstract

Biodegradable nanoarchitectures, with well-defined morphological features, are of great importance for nanomedical research; however, understanding (and thereby engineering) their formation is a substantial challenge. Herein, we uncover the supramolecular potential of PEG–PDLLA copolymers by exploring the physicochemical determinants that result in the transformation of spherical polymersomes into stomatocytes. To this end, we have engineered blended polymersomes (comprising copolymers with varying lengths of PEG), which undergo solvent-dependent reorganization inducing negative spontaneous membrane curvature. Under conditions of anisotropic solvent composition across the PDLLA membrane, facilitated by the dialysis methodology, we demonstrate osmotically induced stomatocyte formation as a consequence of changes in PEG solvation, inducing negative spontaneous membrane curvature. Controlled formation of unprecedented, biodegradable stomatocytes represents the unification of supramolecular engineering with the theoretical understanding of shape transformation phenomena.

Influence of surface charge on the formulation of elongated PEG-b-PDLLA nanoparticles

“…Nanoparticle morphology is recognised to be a key determinant of performance in the field of nanomedicine. [1][2][3][4][5][6] Contrary to other particle features such as size and surface charge, shape only recently received attention as an important factor determining the behaviour of particles in a biological context. High-aspect ratio nanoparticles have been shown to have improved biophysical properties with regard to for example flow characteristics (influencing circulation and distribution) and interactions with cells/tissues.…”

“…We were able to demonstrate this both for non-degradable block copolymers such as poly(ethylene glycol)-poly(styrene) 25,26 and, more recently, biodegradable block copolymers. 1,27 In this way, we have generated tubular polymersomes (nanotubes) and bowlshaped vesicles known as stomatocytes comprising poly(ethylene glycol)-poly(D,L-lactide) (PEG-b-PDLLA) block copolymers.…”

Adaptive Polymersome and Micelle Morphologies in Anticancer Nanomedicine: From Design Rationale to Fabrication and Proof‐of‐Concept Studies

“…[42] On average, nanoparticles with higher aspect ratios inhibited uptake more extensively compared to spherical particles. [46][47][48] Significantly, shape transformations of spherical PEG-PDLLA polymersomes into both oblate and prolate structures can be induced by an osmotic pressure applied on the membrane during low-temperature dialysis. The DeSimone group developed the PRINT technique, in which a liquid polymer precursor can be molded and cured to form any desired shape, finding that particle design influences cellular integration pathways and cell uptake.…”

“…The ability to engineer polymeric nanoparticles with such interesting morphological characteristics and the capacity to be adapted for, or in response to, specific biological environments is now being harnessed for proof-of-concept biochemical testing both in vitro and in vivo. [47] Copyright 2017, American Chemical Society. A delicate interplay of factors concerning cellular uptake mechanisms, distribution, and tumor accumulation leads to the notion that the morphology of nanoparticles seemingly affects the biodistribution and reduction of tumor volume.…”

“…To this end, van Hest et al explored the utility of biodegradable copolymers for self-assembly to unravel their potential in nanomedical research (Figure 7). [47] With fine-tuning of the selfassembly through systematic engineering of the physical and chemical process, elongated nanotubes and bowl-shaped stomatocytes were prepared from biodegradable subunits. The ability to design such structures from biodegradable components holds great potential for nanomedical applications.…”