Citation: Jie Pan, Shurui Hu, Wenchao Jiang, Junyu Xiao, Xiaogang Liu, Qinglong Qiao, Zhaochao Xu. Phenylethynyl-bridged naphthalimide probe for super-resolution imaging and polarity decoding of lipid droplets[J]. Chinese Chemical Letters, ;2026, 37(9): 112618. doi: 10.1016/j.cclet.2026.112618 shu

Phenylethynyl-bridged naphthalimide probe for super-resolution imaging and polarity decoding of lipid droplets

Jie Pan ^a ,
Shurui Hu ^{a, b} ,
Wenchao Jiang ^a ,
Junyu Xiao ^a ,
Xiaogang Liu ^c ,
Qinglong Qiao ^{a, b, *,} ,
Zhaochao Xu ^{a, b, *,}

a.
State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
b.
University of Chinese Academy of Sciences, Beijing 100049, China
c.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

qqlqiao@dicp.ac.cn

zcxu@dicp.ac.cn

Received Date: 8 March 2026
Revised Date: 11 March 2026
Accepted Date: 12 March 2026
Available Online: 13 March 2026

Figures(5)

Lipid droplets (LDs) serve as central hubs for lipid synthesis, storage, and mobilization, with their biological functions largely governed by the composition of neutral lipid cores. Although in situ probing of LD polarity has emerged as a promising strategy to decode compositional remodeling, probes capable of resolving the subtle and narrowly distributed polarity variations within LD interiors remain scarce. Here we report a phenylethynyl-bridged naphthalimide probe (TS-N) that enables sensitive decoding of LD polarity in living cells. Introduction of a conjugated phenylethynyl spacer significantly increases the intramolecular charge-transfer distance (d_CT = 3.561 Å), resulting in enhanced solvatochromic responsiveness with an emission shift exceeding 220 nm across solvent polarity gradients. The probe exhibits a high polarity sensitivity of 14.5 nm per unit, enabling detection of subtle dielectric variations within weakly polar LD interiors. TS-N selectively targets LDs and supports long-term super-resolution imaging of dynamic processes, including LD fusion and mitochondria-LD interactions. Importantly, quantitative in situ fluorescence spectral analysis reveals that TS-N can resolve metabolic perturbation-induced polarity fluctuations at the single-droplet level and correlate dielectric changes with droplet size remodeling. This strategy integrates structural imaging with compositional decoding, providing a powerful tool for investigating LD metabolic heterogeneity and organelle interactions in living cells.
- Lipid droplets,
- Fluorescent probe,
- Polarity,
- Solvatochromic,
- Super-resolution imaging
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