Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Abstract

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.

Keywords: aggregation-induced emission; cargo transportation; imaging; light-propelled movement; polymersomes.

Scheme 1

Schematic illustration of the self-assembly of PEG₄₄-P(AIE)₈ block copolymers into spherical polymersomes and peanut-shaped polymersomes.

Figure 1

Characterization of spherical polymersomes and peanut polymersomes. (A) Dry-TEM image of spherical polymersomes. Scale bar = 500 nm. (B) Cryo-TEM image of spherical polymersomes. Scale bar = 50 nm. (C) Size distribution of spherical polymersomes measured by dynamic light scattering (DLS). Insert is an optical image of a spherical polymersome solution. (D) Morphological characterization of peanut polymersomes by dry-TEM. Scale bar = 500 nm. (E) Cryo-TEM image of peanut polymersomes. Scale bar = 200 nm. (F) Average size of peanut polymersomes. Insert is an optical image of a peanut polymersome solution.

Figure 2

Characterization of fluorescence of AIEgenic peanut polymersomes. (A) UV-vis absorption spectrum and (B) fluorescence spectrum of peanut polymersomes. Fluorescence characterized by CLSM (λ_Ex = 405 nm) of (C) spherical polymersomes and (D) peanut polymersomes. All scale bars = 20 μm.

Figure 3

Motion behavior of peanut polymersomes and spherical polymersomes upon 405 nm light irradiation. (A) Mean square displacement (MSD) of peanut polymersomes with (1.2 W) and without (0 W) laser irradiation. The velocity of peanut polymersomes was calculated from the equation MSD = (4D)Δt + (V²)(Δt²). (B) Motion performance of spherical polymersomes characterized by their MSD. (C) Diffusion coefficient of peanut and spherical polymersomes at different laser output powers. (D) Representative motion trajectories of peanut polymersomes and spherical polymersomes in the absence/presence of 405 nm laser irradiation. (E) Manipulation of motion behavior by periodic turning on/off of the incident light. Average MSD of peanut polymersomes with 5 cycles of turning on (1.2 W) and off (0 W) the 405 nm light.

Figure 4

Characterization of the interaction between peanut polymersomes and HeLa cells. CLSM images of spherical polymersomes (top) and peanut polymersomes (bottom) in contact with HeLa cells under laser irradiation. To visualize the HeLa cells, the cell membrane was stained with WGA-AF488, which exhibited green fluorescence. Spherical polymersomes and peanut polymersomes showed red fluorescence in the AIE channel. Scale bar = 30 μm.

Figure 5

Evaluation of cell viability in the presence of peanut polymersomes without (top) and with (bottom) laser irradiation. Green fluorescence was from calcein-AM and represents the live cells. Red fluorescence shows the dead cells, which were stained by PI. Scale bar = 50 μm.