Purely organic light-harvesting phosphorescence energy transfer by β-cyclodextrin pseudorotaxane for mitochondria targeted imaging

Abstract

A new type of purely organic light-harvesting phosphorescence energy transfer (PET) supramolecular assembly is constructed from 4-(4-bromophenyl)-pyridine modified β-cyclodextrin (CD-PY) as a donor, cucurbit[8]uril (CB[8]) as a mediator, rhodamine B (RhB) as an acceptor, and adamantane modified hyaluronic acid (HA-ADA) as a cancer cell targeting agent. Interestingly, the complexation of free CD-PY, which has no RTP emission in aqueous solution, with CB[8] results in the formation of CD-PY@CB[8] pseudorotaxane with an RTP emission at 510 nm. Then the addition of RhB leads to an efficient light-harvesting PET process with highly efficient energy transfer and an ultrahigh antenna effect (36.42) between CD-PY@CB[8] pseudorotaxane and RhB. Importantly, CD-PY@CB[8]@RhB assembles with HA-ADA into nanoparticles with further enhanced delayed emission at 590 nm. The nanoparticles could be successfully used for mitochondria targeted imaging in A549 cancer cells. This aqueous-state PET based on a supramolecular assembly strategy has potential application in delayed fluorescence cell imaging.

Scheme 1. Construction of the supramolecular assembly for a purely organic light-harvesting PET system and related molecules.

Fig. 1. ¹H NMR titration spectra (400 MHz, D₂O, 298 K) of CD-PY (1.0 mM) in the presence of (a) 0.00, (b) 0.25, (c) 0.50, and (d) 0.70 equiv. of CB[8].

Fig. 2. The prompt photoluminescence (a and c) (inset of (c): the enlarged luminescence peak at 510 nm) and gated (0.1 ms) spectra (b) of CD-PY with or without CB[7,8] and N₂ in aqueous solution. (d) Decay curve of CD-PY@CB[8] (1 : 0.5) aqueous solution at 510 nm ([CD-PY] = 0.5 mM, Ex = 340 nm, 298 K).

Fig. 3. (a) Normalized absorption spectrum of β-CD@RhB and the gated emission spectrum of CD-PY@CB[8] (1 : 0.5). (b) Gated spectra (0.1 ms) of CD-PY@CB[8] (1 : 0.5) in aqueous solution with different concentrations of RhB. Inset: (1) Photographs of CD-PY@CB[8] (1 : 0.5), and (2) CD-PY@CB[8]@RhB (1 : 0.5 : 0.02) under UV light (365 nm). (c) Gated spectra (0.1 ms) of CD-PY@CB[8]@RhB (1 : 0.5 : 0.02) from 298 to 200 K. (d) Decay curve of CD-PY@CB[8]@RhB (1 : 0.5 : 0.02) at 590 nm at 200 K. (e) A possible mechanism diagram of the phosphorescence energy transfer (PET) process for the CD-PY@CB[8]@RhB system (Abs. stands for absorption, ISC for intersystem crossing, Fluo for fluorescence, Phos for phosphorescence and DF for delayed fluorescence). ([CD-PY] = 0.5 mM, Ex = 340 nm, Ex. slit = 10, Em. slit = 10, 298 K).

Fig. 4. (a) Gated spectra of CD-PY@CB[8]@RhB (1 : 0.5 : 0.02), CD-PY@CB[8]@RhB@HA-ADA (1 : 0.5 : 0.02 : 0.31), CD-PY@RhB@HA-ADA (1 : 0.02 : 0.31), and RhB@HA-ADA (0.02 : 0.31). (b) Decay curves of CD-PY@CB[8]@RhB@HA-ADA (1 : 0.5 : 0.02 : 0.31) at 580 nm ([CD-PY] = 0.5 mM, Ex = 340 nm, Ex. slit = 10, Em. slit = 20, 298 K).

Fig. 5. (a) Schematic illustration of the formation of supramolecular nanoparticles. (b) TEM image and (c) zeta potential of CD-PY@CB[8]@RhB@HA-ADA. (d) Laser confocal images of A549 cells co-stained with (1) Mito-Tracker Green, and (2) CD-PY@CB[8]@RhB@HA-ADA (1 : 0.5 : 0.02 : 0.31) ([CD-PY] = 0.005 mM); (3) merged image of (1) and (2).