The advancement of targeted drug delivery faces significant challenges for clinical translation, such as issues related to poor solubility, non-specific distribution, and limited bioavailability of cancer theranostics. Notably, promising developments in near-infrared (NIR) imaging, particularly those centered around Indocyanine Green (ICG), hold the potential for intraoperative tumor targeting. However, the field of medical imaging grapples with two persistent challenges: 1) non-targeted uptake and 2) incomplete elimination of imaging agents. In response to these issues, we focus on the creation of targeted NIR-I/II fluorescence agents possessing optimized physicochemical properties. These innovative compounds encompass zwitterionic organic nanocarriers, such as the noteworthy Harvard Dots (H-Dots). Importantly, these agents can be administered systemically, circumventing non-specific tissue uptake and achieving exclusive elimination through the urinary system. H-dots not only enable the precise determination of surgical margins through NIR image-guided procedures but also serve as effective carriers for targeted anticancer drug delivery. Their unique characteristics result in reduced uptake by the immune system, heightened selectivity for tumors, and enhanced tumor suppression compared to conventional free drugs. Consequently, these H-Dots represent a highly promising theranostic nanoplatform. This research paves the way for the creation of renal-clearable, tissue-specific NIR contrast agents, holding great promise for future advancements in image-guided cancer surgery and, ultimately, improved patient outcomes.
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