Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes

Abstract

Polymersomes are robust, versatile nanostructures that can be tailored by varying the chemical structure of copolymeric building blocks, giving control over their size, shape, surface chemistry, and membrane permeability. In particular, the generation of nonspherical nanostructures has attracted much attention recently, as it has been demonstrated that shape affects function in a biomedical context. Until now, nonspherical polymersomes have only been constructed from nondegradable building blocks, hampering a detailed investigation of shape effects in nanomedicine for this category of nanostructures. Herein, we demonstrate the spontaneous elongation of spherical polymersomes comprising the biodegradable copolymer poly(ethylene glycol)-b-poly(d,l-lactide) into well-defined nanotubes. The size of these tubes is osmotically controlled using dialysis, which makes them very easy to prepare. To confirm their utility for biomedical applications, we have demonstrated that, alongside drug loading, functional proteins can be tethered to the surface utilizing bio-orthogonal “click” chemistry. In this way the present findings establish a novel platform for the creation of biocompatible, high-aspect ratio nanoparticles for biomedical research.

Engineering Polymersomes for Diagnostics and Therapy

“…[71] This shape transformation was controlled osmotically using dialysis against aqueous solutions with varying concentrations of sodium chloride. At salt concentrations of 10 and 50 mM, elongated nanotubes were mainly observed.…”

Designing Molecular Building Blocks for Functional Polymersomes

“…The main challenge is the compatibility prediction of different polymers. Polymersomes are usually prepared with the racemic poly(D,L‐lactide) . Applying PLA stereocomplexation in polymersomes can potentially incorporate modulation of physical properties by changing the ratio between PDLA and PLLA.…”

“…Preferably, the conjugation reaction should be high yielding, chemoselective, and proceed under mild conditions that do not impact the shape or form of the nanostructure. Following these requirements, many block‐copolymers have been functionalized via an appropriate linker or complementary reactive group . This can be achieved via direct polymerization of reactive handles to monomers, or by making use of functional initiators.…”

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.…”