Poly(ε-caprolactone)-containing graft copolymers for ratiometric extracellular oxygen sensing

Abstract

a b s t r a c tA graft copolymer composed of poly(ε-caprolactone) as a hydrophobic chain and poly(N-(2-hydroxypropyl)methacrylamide) as a hydrophilic segment with an internal reference probe for oxygen sensing was prepared. Highly efficient platinum(II)meso-tetra(pentafluorophenyl)porphine (PtTFPP) was used as a typical oxygen probe. Although PtTFPP was highly efficient, it is hydrophobic, limiting its direct application for oxygen sensing in biological conditions. By using the amphiphilic graft copolymer, PTTFPP was successfully incorporated into the micelles formed by this polymer to not only enable the application of PtTFPP for biosensing in medium but also retain its high efficiency. The quantum efficiency of PtTFPP in the micelle solution under nitrogen can reach as high as 0.20. The PtTFPP-containing micelles were tested for high throughput cell respiration and bacteria detection. The influence of an antibiotic, antimycin as a representative example, on cell respiration was also studied. For achieving high accurate sensing, an internal built-in reference probe with aggregation induced emission properties were also polymerized in the graft copolymer. This study demonstrated that the graft polymer approach is a good way to enable highly efficient and hydrophobic oxygen probes for biosensing.

Extracellular Oxygen Sensors Based on PtTFPP and Four-Arm Block Copolymers

“…In this article, we introduce a novel multi-arm amphiphilic oxygen-sensitive probe for real-time measurement of dissolved oxygen concentration in extracellular or aqueous solutions. Compared with previous studies [27], ring-opening polymerization has the advantages of simple operation, high yield, and low cost. Furthermore, unlike linear polymers, multi-arm PEG that has higher terminal group concentrations than conventional linear polymers [35] is used, which enables the further modification or functionalization of the multi-arm polymers.…”

“…Micelles containing oxygen probes were prepared according to the method described in reference [27]. Generally, 1 mg of PtTFPP and 15 mg of polymer were dissolved in 600 µL of tetrahydrofuran and slowly injected the mixed solution into 3 mL of MilliQ distilled water stirred at high speed (1400 rpm) to form a uniform and transparent micelle solution.…”

“…Since 2012, in order to enable the application of hydrophobic probes in biological research, we have started to use micelles formed by amorphous block copolymers to encapsulate highly efficient hydrophobic oxygen probes. At present, we mainly use amphiphilic polymers, including grafted polymers [27,28] and simple block copolymers [29]. The quantum yields of platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorophenyl)-porphyrin (PtTFPP) in these micelles depend on whether there is energy transfer in the micelles [28] and the structures of the polymers [29], which are approximately between 0.107 and 0.231.…”

Amphiphilic Fluorine-Containing Block Copolymers as Carriers for Hydrophobic PtTFPP for Dissolved Oxygen Sensing, Cell Respiration Monitoring and In Vivo Hypoxia Imaging with High Quantum Efficiency and Long Lifetime

“…In the respiration detection, we also used a plate reader to collect the changes in phosphorescence intensity over time among different densities of E. coli . At the early stage of the experiment, the emission intensity will decrease due to the temperature equilibrating issue or temperature effect [ 26 , 27 ], so we stabilized the samples for 20 min before the detection.…”

“…In order to enable the application of PtTFPP and its derivatives for biostudies, scientists have explored a few approaches along this direction, including the generation of nanoparticles with the assistance of conjugated polymers [ 19 , 20 ], the conjugation of PtTFPP-derivatives into the main-chain of conjugated polymers [ 21 , 22 , 23 ], and the encapsulation of the porphyrin probe into the micelles formed from amphiphilic block or graft copolymers [ 24 ], etc. We have been using the micelle approach to transfer PtTFPP into aqueous solution for oxygen sensing by using linear block copolymer and graft copolymers [ 25 , 26 , 27 ]. However, there is no systematical investigation of structure-property relationships.…”