Aromatic vs. aliphatic linkers: impact on dye loading and stability in oligoglycerol-derived dendronized polymersomes

Abstract

Nanocarriers protect the payload from degradation and enable specific targeting of the diseased tissue, thus reducing systemic toxicity. So, it is crucial and desirable to design a nanocarrier with specific nano-architectures that possess those essential characteristics. Considering the above aspects, 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, the 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 polymer ARM-PTU-G₁-OH had a 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 that 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 polymersomes was probed by encapsulating the hydrophilic dye calcein. Both the polymers were able to encapsulate calcein. Among them, the aromatic linker-containing polymer had 31% encapsulation efficiency, whereas the aliphatic linker-containing polymer had 14% encapsulation efficiency. To understand the stability of the polymersomes, a FRET study was performed by encapsulating DiO and DiI dyes individually in both the polymersomes, and 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 that in ARM-PTU-G₁-OH dye exchange occurred via a slow merging and splitting mechanism. In contrast, in ALP-PTU-G₁-OH, a fast expulsion and insertion mechanism was mainly operative.