Cancer cell aggregate hypoxia visualized in vitro via biocompatible fiber sensors

Abstract

To fully understand biological behavior in vitro often dictates that oxygen be reported at either a local or a cellular level. Oxygen sensors based on the luminescent quenching of a specific form of electrospun fiber were developed for measurement of both gaseous and dissolved oxygen concentrations. Electrospinning was used to fabricate "core-shell" fiber configurations in which oxygen-sensitive transition-metal porphyrin complexes are embedded in an optically clear, gas permeable polycarbonate polymer 'core' while polycaprolactone provided a protective yet biocompatible 'shell'. By taking advantage of the resulting high sensitivity and fast response of electrospun core-shell fiber sensors, we were able to locate and image hypoxic regions in contact with aggregates of glioblastoma cells. Nanoscale, biomimetic sensors containing oxygen-sensitive porphyrins are particularly well suited to biological applications. These 'smart' nanofiber based sensors do not consume oxygen, their mechanical and chemical characteristics can be finely tuned allowing tailoring of biocompatibility and microstructure. Core-shell nanofiber oxygen sensing fibers could provide real-time assessments of tumor cell response to pharmacological innovations designed to target hypoxic regions driving new knowledge and technological advancement.

Nanoscale upconversion for oxygen sensing

“…However, there may be some applications in which collocation of both components in the core may be preferred as it could help minimize Ru(dpp)3Cl2 leaching. [4] Optical oxygen sensors based on transition metal complexes, such as Ru(dpp)3Cl2, have many promising qualities, but their reliance on violet or blue excitation wavelengths limits their use in biological applications as such wavelengths undergo high levels of scattering and absorption in biological tissue. [54] Here, we have demonstrated an alternative method to excite Ru(dpp)3Cl2 using 980 nm NIR light via a 'handshake' interaction with UCNPs in core-shell electrospun fibers.…”

“…A potential specific application is the identification of hypoxic regions generated by cancerous tumors either in vivo or in vitro. [4] This ability would be especially relevant in detecting recurrence of glioma brain tumors. Gliomas often recur either at the original tumor site or within 2-3 cm.…”

“…We have incorporated UCNPs (LiYF4:Yb,Tm) with the oxygen-sensitive molecule tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II) dichloride (Ru(dpp)3Cl2) into electrospun core-shell fibers. Despite the longer lifetimes and, therefore, increased oxygen-sensitivity of such porphyrins as palladium (II) and platinum (II) tetrakis(pentafluorophenyl)porphyrin (PdTFPP and PtTFPP), [4,25] Ru(dpp)3Cl2 was chosen due to its broad absorption peak that overlaps efficiently with the upconverter emission at 480 nm. [26][27][28] The detailed electronic interactions between the UCNPs and the ruthenium complex are shown in Figure 1.…”

Fabrication and characterization of metal stent coating with drug-loaded nanofiber film for gallstone dissolution

“…[12][13][14][15][16][17] Electrospun nanofibers showed excellent properties such as fabulous mechanical performance, porous structure, high surface-area-to-volume ratio, and mimicking to biological nanofibrous configuration of the native extracellular matrix (ECM). Such excellent characteristics of electrospun nanofibers make them most suitable applicant for various fields, such as adsorbent and catalyst, 11,18 photoelectric conversion and energy storage, 19 biological detection, 20 biosensors, 21 drug delivery, 22 tissue engineering 23,24 and have brought huge economic benefits to society. Nanofibers as a reservoir for storing drugs have a bright prospect in controlling drug release and some new nanofiber drug delivery system (DDS) have attracted more attention towards sustained and stable release of drug which is crucial to maximum therapeutic effectiveness and minimum potential toxicity.…”

Upconverter-powered oxygen sensing in electrospun polymeric bilayers

“…[2] In addition, cancerous tumors possess highly heterogeneous levels of oxygen, and cells residing within hypoxic regions characterized by extremely low oxygen concentration better resist radiation and chemotherapy. [3,4] The biophotonic reporting of oxygen content in biological environments is desired for both in vitro and in vivo (i.e., under-the-skin) applications. Thus, optical oxygen sensors based on luminescent quenching phenomena are attractive for these applications as they are easily miniaturized and show many desirable properties, including rapid response, decreased toxicity and improved sensitivity.…”