納米級藥物遞送系統（DDS）由於其諸多優點，如控制釋放、高效性和特異性靶向，廣泛應用於癌症治療中。通過運載熒光染料，納米DDS可以進一步增強其熒光成像能力。熒光染料的使用可實現對腫瘤部位的精確成像和監測，促進靶向藥物遞送，並實時評估治療反應。

然而，如果將常規熒光染料大量引入納米顆粒中，可能會出現所謂的聚集引起猝滅（ACQ）現象，顯著降低其成像能力。最近，通過使用特定的聚集誘導發光（AIE）染料，找到了解決ACQ問題的方法。在過去幾年中，已開發了許多基於AIE的熒光納米顆粒，利用物理封裝或共價連接的AIE染料。這些創新平台已在藥物遞送、光療和細胞成像應用中得到有效利用。

本研究設計了一種以透明質酸為基礎的R6新藥前藥，並具有AIE特性。該前藥能在水溶液中形成納米顆粒（NP），激活R6基團的AIE特性。這些顆粒在腫瘤微環境（TME）酸性條件下釋放R6（72小時後釋放率達99%），並在生理pH下保持穩定。此外，通過顯微鏡觀察到AIE的熒光信號。透明質酸殼層可以靶向過表達的癌細胞CD44受體，使NP具有活性靶向特性。該前藥對小鼠乳腺癌細胞系4T1具有毒性，對L929成纖維細胞無害。熒光顯微鏡圖像證實了NP在4T1細胞中的成像能力。透明質酸-R6聚合物前藥有望成為一種多功能的pH敏感藥物遞送平台

Nanosized drug delivery systems (DDS) are widely utilized in cancer therapy due to their numerous advantages, such as controlled delivery, high efficacy, and site-specific targeting. Nano-DDS can be further enhanced by the incorporation of fluorescence imaging capabilities, by delivering fluorescence dyes. The use of fluorescence dyes allows for precise imaging and monitoring of the tumor site, facilitating targeted drug delivery and enabling real-time assessment of therapeutic response.
Nevertheless, if conventional fluorescent dyes are incorporated in nanoparticles in high quantities, they can experience a phenomenon known as aggregation-caused quenching (ACQ), significantly impairing their imaging capacity. Recently, a solution to the ACQ issue has been found through the use of specific aggregation-induced emission (AIE) dyes. Over the past few years, numerous AIE-based fluorescent nanoparticles have been developed, utilizing either physically encapsulated or covalently attached AIE dyes. These innovative platforms have been effectively utilized in drug delivery, phototherapy, and cellular imaging applications.
In this work, a hyaluronic acid-based prodrug of the novel drug R6 was designed with AIE properties. The prodrug was able to form nanoparticles (NP) in an aqueous solution, which activated the AIE properties of pendant R6 groups. The particles released R6 at the tumor microenvironment (TME) acidic condition (99% release after 72 hours) and remained stable at the physiological pH. In addition, fluorescence signals by AIE were detected by microscopy. The hyaluronic acid shell can target the overexpressed CD44 receptors in cancer cells, which gives the NP active targeting property. The prodrug showed toxicity against the mouse breast cancer cell line 4T1 while being harmless to the L929 fibroblast cells. Fluorescence microscopy images confirmed the imaging ability of the NP in 4T1 cells. The HA-R6 polymer prodrug promises to be a versatile pH-sensitive drug delivery platform

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