文献：Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer

文献链接：https://link.springer.com/article/10.1186/s12951-021-00891-8

作者：Yinan Ding , Rui Yang , Weiping Yu , Chunmei Hu , Zhiyuan Zhang, Dongfang Liu, Yanli An , Xihui Wang , Chen He , Peidang Liu , Qiusha Tang , Daozhen Chen

相关产品：CO-FITC（羰基-FITC）

FITC-CO-HPPH-TH302/Lipo（FITC-羰基-HPPH-TH302-脂质体）

原文摘要：

Triple negative breast cancer (TNBC) is an aggressive tumor with extremely high mortality that results from its lack of effective therapeutic targets. As an adhesion molecule related to tumorigenesis and tumor metastasis, cluster of differentiation-44 (also known as CD44) is overexpressed in TNBC. Moreover, CD44 can be effectively targeted by a specific hyaluronic acid analog, namely, chitosan oligosaccharide (CO). In this study, a CO-coated liposome was designed, with Photochlor (HPPH) as the 660 nm light mediated photosensitizer and evofosfamide (also known as TH302) as the hypoxia-activated prodrug. The obtained liposomes can help diagnose TNBC by fluorescence imaging and produce antitumor therapy by synergetic photodynamic therapy (PDT) and chemotherapy. Compared with the nontargeted liposomes, the targeted liposomes exhibited good biocompatibility and targeting capability in vitro; in vivo, the targeted liposomes exhibited much better fluorescence imaging capability. Additionally, liposomes loaded with HPPH and TH302 showed significantly better antitumor effects than the other monotherapy groups both in vitro and in vivo. The impressive synergistic antitumor effects, together with the superior fluorescence imaging capability, good biocompatibility and minor side effects confers the liposomes with potential for future translational research in the diagnosis and CD44-overexpressing cancer therapy, especially TNBC.   

CO-FITC：FITC 是一种在生物化学和细胞生物学等领域使用的荧光染料，它能与生物分子（如蛋白质、抗体等）共价结合，用于标记和追踪这些分子。“CO”是一个连接基团，可能会改变 FITC 的某些化学性质，如溶解性、与目标分子的结合能力或者荧光特性等。

FITC-CO-HPPH-TH302/Lipo：FITC（异硫氰酸荧光素）：它是一种荧光染料。在这个组合中，主要用于标记和追踪目的。它可以在特定波长的光激发下发出荧光，方便观察复合物在生物体系中的位置、分布和运输等情况。CO起到连接 FITC 和 HPPH - TH302 的作用，使得不同的分子能够组合在一起形成一个新的复合物。HPPH - TH302：这可能是一种具有特定药理作用的化合物。HPPH 通常是一种光敏剂，在光动力Treatment （PDT）中有应用。TH302 是一种缺氧激活前药，在tumour的缺氧区域能够被激活发挥抗cancer作用。二者结合可能是为了综合利用 HPPH 的光动力特性和 TH302 的缺氧激活特性来Treatment tumour。Lipo（脂质体）：脂质体是一种人工膜，通常由磷脂双分子层组成。它在化合物递送系统中有应用。在这个组合中，脂质体可能是作为载体，包裹 FITC - CO - HPPH - TH302 复合物，提高化合物的稳定性、生物相容性和靶向性。基于CO-FITC、FITC-CO-HPPH-TH302/Lipo的性能，多功能化合物CO-HPPH-TH302/Lipo的合成如下：

图：合成示意

HPPH脂质的合成：

将LPC、HPPH、EDC、DAMP和DIPA混合在无水二氯甲烷中。反应混合物在室温氩气下黑暗搅拌，用二醇改性二氧化硅（Sorbtech）纯化，用甲醇在DCM中洗涤杂质后，用甲醇在DCM中洗脱。然后将HPPH脂质在氮气下干燥，并在氩气中等分储存。采用HPLC-MS /MS，C8柱对HPPH脂质纯度进行分析。

脂质体的制备：

将LPC、胆固醇、HPPH脂质、TH302和CO-OA按一定质量比溶解于氯仿和甲醇中，用旋转蒸发器干燥，制备CO-HPPH-TH302/Lipo。然后，用磷酸盐缓冲盐水（PBS）水化干燥的脂膜，并搅拌。通过Millipore 去除未包封的TH302、HPPH和CO-OA，分子量切断。其余脂质体：自由脂质体、co -脂质体、TH302/Lipo、CO-TH302/Lipo、HPPH/Lipo、CO-HPPH/Lip和HPPH-TH302/Lipo按相同的工艺制备。

图：表征

结论：

该文献成功制备出基于CO-FITC、FITC-CO-HPPH-TH302/Lipo合成的多功能化合物CO-HPPH-TH302/Lipo。它有效地结合了CD44靶向、荧光成像、光动力Treatment 和缺氧激活的前药协同Treatment 。这种协同疗法成功地扩大了每个单独heal的效果，并减少了体外和体内的副作用。新型纳米颗粒具有良好的生物相容性和良好的破坏能力。总之，CO-HPPH-TH302/Lipo可以作为cd44过表达tumour（如TNBC）的诊断和Treatment 载体，是有效的策略。