Aromatic vs. Aliphatic Linkers: Impact on Dye Loading and Stability in Oligoglycerol-Derived Dendronized Polymersomes

The nanocarrier protects the payload from degradation and enables specific targeting of diseased tissue, thus reducing systemic toxicity. So, it is crucial to design a nanocarrier with specific nano-architectures that possess those essential characteristics, which is very much desired. Considering those here, we report the one-pot synthesis and self-assembly of oligoglycerol-based amphiphilic dendronized polythiourethanes consisting of an aliphatic or aromatic linker. During the ring opening of cyclodithiocarbonate, generated thiols were utilized to conjugate first or zeroth-generation oligoglycerol dendrons (containing four or two hydroxyl groups) in one pot. Among them, the aromatic linker containing ARM-PTU-G1-OH had higher encapsulation ability for hydrophobic dyes (pyrene and Nile red) than the other aliphatic linker containing polymer ALP-PTU-G1-OH. Both the polymers had hydrodynamic diameters of 167 nm with PDI 0.314-0.326. In addition, AFM results showed ALP-PTU-G1-OH and ARM-PTU-G1-OH formed spherical aggregates with diameters of 136 ± 28 nm and 161 ± 35 nm, respectively. The formation of polymersome was probed by encapsulating hydrophilic dye calcein. Both the polymers were able to encapsulate calcein. Among them, aromatic linker-containing polymer had 31 % encapsulation efficiency, whereas aliphatic linker polymer had 14 %. To understand the stability of polymersomes formed, the FRET study was performed by encapsulating DiO and DiI dyes individually in both the polymersomes, then mixing and studying the evolution of FRET with time. The results showed that the mechanism of dye exchange was different for both polymers, and the aromatic linker containing polymersome had better stability during dye exchange. A few parameters were calculated by fitting the change in donor emission intensity with time, and it showed ARM-PTU-G1-OH had dye exchange via a slow merging and splitting mechanism. In contrast, in ALP-PTU-G1-OH, the fast expulsion and insertion mechanism was mainly operative.