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Microelectrodes offer exceptional sensitivity, rapid response, and versatility, making them ideal for real-time detection and monitoring applications. Photoelectrochemical (PEC) sensors have shown great value in many fields due to their high sensitivity, fast response, and ease of operation. Nevertheless, conventional PEC sensing relies on cumbersome external light sources and bulky electrodes, hindering its miniaturization and implantation, thereby limiting its application in real-time disease monitoring. To overcome these limitations, we developed a nanoencapsulated optical fiber (OF)-based PEC microelectrode. The microelectrode features TiO 2 /CdS nanocrystals and bis (2,2'-bipyridine) (10-methylphenanthroline [3,2- a :2'3'- c ] pyridine ruthenium(II) dichloride ([Ru(bpy) 2 dppz] 2+ ) @dsDNA/Au@epigallocatechin gallate nanoparticle (EGCG NP) layers. And its application for the detection of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a biomarker of cardiovascular diseases was explored. An extensive linear range of 1-5000 pg mL -1 combined with a low detection limit of 0.36 pg mL -1 was achieved. This range covers not only the recommended threshold for excluding cardiovascular diseases in the clinical diagnosis of individuals across all age groups but also the prognostic target value. The sensor exhibited excellent selectivity and stability and notable labeling recovery capability in serum tests. Critically, the sensor successfully discriminated the alterations in NT-proBNP secretion levels within human smooth muscle cells, comparing pre- and poststimulation by platelet-derived growth factor-BB. Even more significantly, the skin puncture experiment conducted in mice demonstrated the remarkable implantability and biological compatibility of the OF-PEC microelectrode. This addresses critical challenges commonly faced by microelectrodes when used as implanted devices, such as minimizing invasive trauma, mitigating inflammation, and preventing biofouling, thereby firmly establishing their suitability for the development of advanced implantable sensing devices. Therefore, the present OF microelectrode PEC biosensor is not only cost-effective, easy to operate, and miniaturized but also holds significant potential for enabling more precise, more minimally invasive, and continuous monitoring of biological markers without causing inflammation. This capability is crucial for early disease detection, tracking disease progression, and facilitating personalized treatment strategies, which expands the practical application of PEC sensors.