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This process involves complex physical changes and molecular transformations within lysosomes; however, the particle\u2010to\u2010molecule transition\u2013defined here as \u201cnanometabolism\u201d\u2013has remained difficult to quantify due to intrinsic limitations of nanoscale bioimaging. To circumvent the fluorescence quenching of conventional fluorophores and the challenges of observing nanoscale dynamics, peak\u2010shifted, dual\u2010state emissive nanoprobes composed entirely of donor\u2013acceptor bithiophene dyes are introduced here. This approach establishes a highly adaptable design strategy for constructing heterogeneous organic nanoparticles templated by these molecular metrics. These molecular probes generate bright, ratiometric spectral shifts that directly encode nanoparticle disassembly, enabling robust optical monitoring of intracellular nanometabolism with cell\u2010type\u2010 and particle\u2010size\u2010resolution. Time\u2010resolved imaging identifies protonation\u2010induced lysosomal membrane destabilization as the primary driver of nanoparticle breakdown within 6\u201312\u00a0h. Supported by cryogenic correlative imaging and tissue\u2010level tracking, this platform provides a promising optical framework for monitoring nanometabolism in living systems. It serves as a pivotal breakthrough in elucidating the mechanistic design rules required for the future development of carrier\u2010free nanomedicines with predictable intracellular behavior.<\/jats:p>","DOI":"10.1002\/advs.77509","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:05:08Z","timestamp":1788757508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Visualization of Intracellular Nanometabolism Using Peak\u2010Shifted Dual\u2010State Emissive FRET Nanoprobes"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-9226","authenticated-orcid":false,"given":"Farsai","family":"Taemaitree","sequence":"first","affiliation":[{"name":"Research Institute for Electronic Science and Division of Information Science and Technology Hokkaido University  Sapporo 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