Polymer Nanoassemblies With solvato- and halo-fluorochromism for Drug Release Monitoring and Metastasis Imaging

Abstract

Background: Theranostics, an emerging technique that combines therapeutic and diagnostic modalities for various diseases, holds promise to detect cancer in early stages, eradicate metastatic tumors and ultimately reduce cancer mortality. Methods & results:This study reports unique polymer nanoassemblies that increase fluorescence intensity upon addition of hydrophobic drugs and either increase or decrease fluorescence intensity in acidic environments, depending on nanoparticle core environment properties. Extensive spectroscopic analyses were performed to determine optimal excitation and emission wavelengths, which enabled real time measurement of drugs releasing from the nanoassemblies and ex vivo imaging of acidic liver metastatic tumors from mice. Conclusion: Polymer nanoassemblies with solvato-and halo-fluorochromic properties are promising platforms to develop novel theranostic tools for the detection and treatment of metastatic tumors.

Development of Halofluorochromic Polymer Nanoassemblies for the Potential Detection of Liver Metastatic Colorectal Cancer Tumors Using Experimental and Computational Approaches

“…These PNAs were synthesized according to previously reported methods (26–28, 30, 31, 46). Briefly, scaffolds (PEI or PLL) were reacted with NHS-activated PEG first in a mixed reaction solvent (water:DMSO:pyridine = 2:1:1) at room temperature for 2~3 days.…”

“…NB and IR820 were conjugated to the primary amines in the core of PNAs by reacting the dyes with PEG-PEI-PAL or PEG-PLL-PAL in methanol at 40°C overnight in the presence of pyridine scavenging hydrochloric acid byproducts as previously reported (47). Alexa546 was conjugated to PEG-PLL-PLA through the NHS coupling reaction in DMSO at room temperature overnight.…”

“…Alexa546 was conjugated to PEG-PLL-PLA through the NHS coupling reaction in DMSO at room temperature overnight. PEG-PEI( # ) scaffold having no PAL was also used as comparison to determine the effect of PNA core environment with charge on halofluorochromism of the NB-conjugated particles (27, 28). All dye-labeled PNAs were dialyzed in water, purified by size exclusion gel columns, and collected by freeze-drying.…”

“…We recently verified that PNAs entrapping imaging dyes that change fluorescence as a function of solvent pH (halofluorochromism) would be particularly useful to elucidate how nanoparticles distribute in tumors with acidic tissue environments(28, 35). Tumor tissue is acidic as rapidly proliferating cancer cells produce a large amount of lactic acid during proliferation.…”

“…The acidic tumor tissue can be used to trigger drug release from nanoparticle carriers or differentiate tumor from normal tissue by using halofluorochromic dyes such as Nile blue (NB). Our previous observations revealed that NB quenches its fluorescence in water but remains fluorescent in the core of PNAs while the dye-loaded PNAs change fluorescence wavelength and intensity in response to environmental pH (26–28). We hypothesize that NB-loaded PNAs may detect subtle changes in tissue pH and thus allow for early and accurate detection of small liver metastatic CRC tumors for intraoperative imaging.…”