Stiffness‐Dependent Intracellular Location of Cylindrical Polymer Brushes

Abstract

Cylindrical polymer brushes (CPBs) are macromolecules with nanoparticle proportions. Their modular synthesis enables tailoring of their chemical composition as well as the dialing‐up of overall dimensions and physicochemical properties. In this study, two rod‐like poly[(ethylene glycol) methyl ether methacrylate] (PEGMA)‐based CPBs with varying stiffness but otherwise comparable features and functionality, are synthesized. Differences in particle stiffness are assessed using small angle neutron scattering (SANS). It is observed that the fate of the two CPBs within cells is distinctly different. Stiffer CPBs seem to gravitate toward the mitochondria, whereas CPBs with reduced stiffness are present in different intracellular vesicles.

Polymeric Nanotubes as Drug Delivery Vectors─Comparison of Covalently and Supramolecularly Assembled Constructs

“…A BB of the aspect ratio of ∼4–5 was found to give the highest penetration into spheroid models when compared to spherical or filamentous counterparts, 24 and in further work, it was found that the BB stiffness is also an important parameter, whereby particles of high stiffness showed preferential cellular localization into the mitochondria. 25 …”

Molecular polymer bottlebrushes in nanomedicine: therapeutic and diagnostic applications

“…76 The Mu ¨llner team found that the intracellular processing of rod-like MPBs was different depending on their stiffness, with stiffer nanorods preferentially associated with mitochondria whereas more flexible analogues with otherwise comparable dimensions and surface chemistry would be found in more localised compartments in the cytoplasm. 148 Mu ¨llner's study introduced small-angle neutron scattering (SANS) to probe the stiffness differences of nano-rods via their differing Kuhn length, an exercise that is not yet frequently used in this context, but may offer additional insights in correlation to the imaging of nanomaterials. The Chen group synthesised two MPBs analogues that only differed in the shell architecture, namely either with linear PEG chains or comb-like POEGA chains.…”

“…151,167 Internalisation may not differ much from other polymeric nanomaterials, but MPBs allow for tailoring key attributes (beyond surface chemistry) that affect intracellular processing. The shape and stiffness/elasticity of nanoparticles may offer new avenues to influence intracellular processing 42,148,168,169 and inspire mechano-or shape-dependent targeting strategies and immunotherapies. 170 The vast number of cell studies conducted using MPBs to date (including on many different cell lines) indicate that MPBs can be designed to minimise cellular interaction as well as promote it.…”

“…Given that the MPBs are nanoparticles, dynamic light scattering (DLS), or transmission electron microscopy (TEM) are frequently utilised. However, these offer a poor reflection of the solution conformation of MPBs which may appear sphere-like in DLS or TEM, but a deeper study of their shape via small-angle neutron scattering 8,148 or static light scattering 105,182 would give more relevant information, especially if shape or flexibility is the focus of the study. Similarly, specialised cryo-TEM (including tomography) or atomic force microscopy (AFM) in solution may further provide new insights and parameters for structure-function-properties relationships.…”

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

“…A key factor in this regard are formulation strategies, which allow a straightforward imple-mentation into established processes that are, e.g., in accordance with good manufacturing practice (GMP) [6]. Approaches such as the crystallization-driven self-assembly (CDSA) or the synthesis of covalently bound cylindrical polymer brushes (CPBs) offer access to a defined fiber length [7][8][9][10][11][12][13][14][15][16]. However, they also suffer from disadvantages, such as significant experimental effort to evaluate suitable reaction procedures for the synthesis or the conditions for the assembly process, and are therefore often limited to specific materials.…”