Dynamics of dual-fluorescent polymersomes with durable integrity in living cancer cells and zebrafish embryos

Abstract

The long-term fate of biomedical nanoparticles after endocytosis is often only sparsely addressed in vitro and in vivo, while this is a crucial parameter to conclude on their utility. In this study, dual-fluorescent polyisobutylene-polyethylene glycol (PiB-PEG) polymersomes were studied for several days in vitro and in vivo. In order to optically track the vesicles' integrity, one fluorescent probe was located in the membrane and the other in the aqueous interior compartment. These non-toxic nanovesicles were quickly endocytosed in living A549 lung carcinoma cells but unusually slowly transported to perinuclear lysosomal compartments, where they remained intact and luminescent for at least 90 h without being exocytosed. Fluorescence-assisted flow cytometry indicated that after endocytosis, the nanovesicles were eventually degraded within 7-11 days. In zebrafish embryos, the polymersomes caused no lethality and were quickly taken up by the endothelial cells, where they remained fully intact for as long as 96 h post-injection. This work represents a novel case-study of the remarkable potential of PiB-PEG polymersomes as an in vivo bio-imaging and slow drug delivery platform.

Current Perspectives on Synthetic Compartments for Biomedical Applications

“…When these polymersomes were tested on lung carcinoma cells treated with a mixture of antioxidants in 1% oxygen, mimicking the low oxygen concentrations encountered in tumors, the upconversion emission was one order of magnitude higher, proposing a solution to the oxygen sensitivity of TTA-UC systems. Going a step further, PiB- b -PEG polymersomes containing one fluorescent probe in the polymer membrane and a second in the aqueous cavity served for dual fluorescent imaging ( Figure 2 A) [ 168 ]. In lung cancer cells, these polymersomes remained intact for 90 h postinjection and were not exocytosed but did reduce the cell proliferation.…”

“…( A ) Dual fluorescence of polymersomes for optical imaging. Adapted with permission from [ 168 ]. Copyright 2018 Elsevier.…”

The rise of bio-inspired polymer compartments responding to pathology-related signals

“…For example, a specific pathological condition can trigger a detectable color transition or a change in fluorescence in a polymer assembly specifically designed to respond to such changes by the incorporation of dye molecules. 3,[22][23][24][25] Among the novel responsive materials that are being developed as biosensors, polymer systems play a major role because they offer multiple advantages including a large diversity of chemical features, variable molecular weight and composition of the repeating units, changeable functionalities and a variety of architectures. In this review, we present spherical polymer compartments with dimensions from the nano to the microscale and how they are rendered responsive to changes in their environment.…”

Tracing the In Vivo Fate of Nanoparticles with a “Non-Self” Biological Identity

“…Zebrafish embryos have recently emerged as a bioimaging model for preclinical screening of nanomedicines − with an intriguing opportunity of whole-embryo fixation for transmission electron microscopy (TEM) to visualize intracellular trafficking of nanoparticles in vivo at high resolution. , Here, we used the intravital real-time/ultrastructural imaging approaches established previously, and the basic technical and biological knowledge is described therein. Of note is the scavenger phenotype of venous endothelial cells (ECs) that lines the caudal vein (CV) and the CV plexus, the functional analogue of liver sinusoidal ECs in mammals .…”