Natural-Killer-Cell-Inspired Nanorobots with Aggregation-Induced Emission Characteristics for Near-Infrared-II Fluorescence-Guided Glioma Theranostics

Abstract

Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. The "Terminator" in the science fiction film is a cybernetic organism with living tissue over a metal endoskeleton, which inspired us to develop natural-killer-cell-mimic nanorobots with aggregation-induced emission (AIE) characteristics (NK@AIEdots) by coating a natural kill cell membrane on an AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owing to the AIE and soft-matter characteristics of PBPTV, as-prepared NK@AIEdots maintained a superior NIR-II brightness (quantum yield ∼7.9% in water) and good biocompatibility. Besides, they can serve as a tight junction (TJ) modulator to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to form an intercellular "green channel" to help them to cross the blood−brain barrier (BBB) silently. Furthermore, they can initiatively accumulate in glioblastoma cells in the complex brain matrix for highcontrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these NK@AIEdots under the NIR light illumination. As far as we know, the quantum yield of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots showed great potential for BBB-crossing active delivery.

Near‐Infrared‐II Semiconducting Polymer Dots for Deep‐tissue Fluorescence Imaging

“…natural killer (NK) cell-membrane through biomimicking. [21] Excitingly, the formed Pdots revealed the maximum absorption peak at 700 nm with exceptional fluorescence brightness (QỸ 7.9% in an aqueous medium). The presence of NK-cell coating assisted in crossing the blood-brain barrier (BBB) by unzipping the tight-junction modulator for easy in vivo diagnosing the brain-tumors (high contrast (T/NT ratio 60) in comparison to the non-coated Pdots (AIEdots) as shown in Figure 5A.…”

“…Deng et al. developed NK@AIE Pdots from an AIE active PBPTV (Figure 2) semiconducting polymer and enfolded it into a natural killer (NK) cell‐membrane through biomimicking [21] . Excitingly, the formed Pdots revealed the maximum absorption peak at 700 nm with exceptional fluorescence brightness (QY ∼7.9% in an aqueous medium).…”

“…Deng et al developed NK@AIE Pdots from an AIE active PBPTV (Figure 2) semiconducting polymer and enfolded it into a NK@AIE 700 80 7.9 -In vivo performed on orthotropic glioblastoma mice model. Dose: [21] pNIR-4 750 1040 100 2.24 -In vivo delineation blood-vessels with enhanced clarity. [22] P-Pdot 600 1550 28 56 -In vivo through-skull imaging in live mice [23] TTQÀ 2TC NP 1064 900-1400 130 0.03 8,9.5 Dose: 1 mg/ml [24] PttcÀ SeBTaÀ NIR 1380 1082-1290 1300-1400 73 0.05 2.32 In vivo through-skull imaging in live mice.…”

Aggregation‐enhanced theranostics: AIE sparkles in biomedical field

“…More recently, inspired by the design and concept of nanorobots, Tang et al. developed a type of NK‐cell‐mimic AIE NPs (NK@AIEdots) by wrapping the NK cell membranes on AIE‐active polymer‐based NPs [124] . Owing to the AIE feature and soft‐matter characteristics of the conjugated polymer PBPTV, the afforded NK@AIEdots showed superb NIR‐II fluorescence with the QY about 7.9% and good biocompatibility.…”

Gathering brings strength: How organic aggregates boost disease phototheranostics

“…AIEgens are usually twisted structures, and the conjugation is reduced, so it is hard to realize low electronic bandgap or NIR emission 91,92 . Recently, we and other groups have obtained NIR‐II AIEgens by rational molecular design and the utilization of the fundamental rules of Jablonski diagrams 93–98 …”