Near-infrared-emissive polymersomes: Self-assembled soft matter for in vivo optical imaging

Abstract

We demonstrate that synthetic soft materials can extend the utility of natural vesicles, from predominantly hydrophilic reservoirs to functional colloidal carriers that facilitate the biomedical application of large aqueous-insoluble compounds. Near-infrared (NIR)-emissive polymersomes (50-nm-to 50-m-diameter polymer vesicles) were generated through cooperative self assembly of amphiphilic diblock copolymers and conjugated multi(porphyrin)-based NIR fluorophores (NIRFs). When compared with natural vesicles comprised of phospholipids, polymersomes were uniquely capable of incorporating and uniformly distributing numerous large hydrophobic NIRFs exclusively in their lamellar membranes. Within these sequestered compartments, long polymer chains regulate the mean fluorophore-fluorophore interspatial separation as well as the fluorophore-localized electronic environment. Porphyrin-based NIRFs manifest photophysical properties within the polymersomal matrix akin to those established for these high-emission dipole strength fluorophores in organic solvents, thereby yielding uniquely emissive vesicles. Furthermore, the total fluorescence emanating from the assemblies gives rise to a localized optical signal of sufficient intensity to penetrate through the dense tumor tissue of a live animal. Robust NIR-emissive polymersomes thus define a soft matter platform with exceptional potential to facilitate deep-tissue fluorescence-based imaging for in vivo diagnostic and drug-delivery applications.porphyrin ͉ vesicles ͉ nanoscale ͉ diblock copolymer S upramolecular self assembly has revolutionized soft materials research by enabling the efficient and high-throughput fabrication of complex multicomponent nanostructures (1-3). For decades, self-assembled vesicles comprised of phospholipids (liposomes) or small-molecule surfactants (4) have been used for sequestering high concentrations of hydrophilic compounds (5) and controlling their temporal release and distribution for maximal therapeutic efficacy (6). More recently, amphiphilic peptides and polymers have been shown to form very elaborate architectures (7-9) and serve as useful nanocontainers in aqueous solution (10). In particular, self-assembled materials are ideal for carrying promising imaging and therapeutic agents whose biomedical utility has hitherto been hampered by inadequate aqueous solubility (11). Here, we demonstrate the unique ability of synthetic amphiphiles to assemble into functional vesicles that membrane-disperse numerous large hydrophobic fluorophores and enable their specialized application for deeptissue fluorescence-based in vivo imaging.Although visible probes enable exquisite imaging of live animals by intravital microscopy (12), their utility is significantly limited at greater than submillimeter tissue depths as a result of extensive light scattering and optical absorption. Because light scattering diminishes with increasing wavelength, and hemoglobin electronic and water vibrational overtone absorptions approach their nadir over the near-infrared (N...

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

“…Although nanoparticles have been used with a spectrum of different imaging modalities including PET [48,49] and MRI [50][51][52], here we will focus on polymersomes that encapsulate fluorescent agents for optical imaging. Because light scattering decreases with increasing wavelength, and hemoglobin and water absorption spectra have their nadir in the near infrared (NIR) spectral region, much work has been focused on developing NIR contrast agents for in vivo imaging studies [9]. To this end, Ghoroghchian et al have successfully loaded porphyrinbased near infrared fluorophores (NIRFs) into the hydrophobic bilayer membranes of PEO-b-PBD [9,10,53,54], PEO-b-PCL [54], PEO-b-PEE [54], and poly(ethylene oxide)-block-poly (methylcaprolactone) (PEO-bPmCL) [54] polymersomes.…”

“…Studies using PEO-b-PBD polymersomes have shown that porphyrin-based NIRFs, when encapsulated in polymersomes, are able to generate a signal with enough intensity to penetrate through 1 cm of a solid tumor [9]. Further, when these NIR-emissive nanopolymersomes are injected into the tail-vein of mice, the biodistribution of the nanoparticles can be tracked in vivo via non-invasive NIR fluorescence-based optical imaging [55].…”

“…A particularly attractive storage feature, highlighted in Fig. 1, is the large hydrophobic core of the polymersome membrane, which follows from the membrane-forming amphiphilic polymers being larger than conventional phospholipids [9]. Further, block copolymer chemistries can be tuned through polymer synthesis to yield polymersomes with diverse functionality [10].…”

Synthesis and characterization of self-assembled CdHgTe/gelatin nanospheres as stable near infrared fluorescent probes in vivo

“…Briefly, 40 mg of NaBH 4 , 60 mg of tellurium powder and 3.0 mL of H 2 O were added into a small flask in sequence and then the flask was put in a 40 • C water bath. The reacting system was stirred under the protection of N 2 and the black tellurium powder disappeared after 1 h, obtaining a clear purple NaHTe solution.…”

“…Based on this unique deeper tissue-penetrative property as well as non-ionizing and non-radioactive advantages, the research of NIR non-invasive imaging techniques attracted extensive attentions for real time and dynamic monitoring/tracing of biological signals in living animals. As a newly emerged optical technique, NIR imaging was successfully applied in many frontier fields of life sciences, such as nanomedicine research [3,4], cancer diagnosis and treatment [5,6] in recent years.…”