Therapeutic sponge prevents postoperative breast cancer recurrence by sustainably dissociating into CD44-targeted nanoplatform
Therapeutic sponge prevents postoperative breast cancer recurrence by sustainably dissociating into CD44-targeted nanoplatform
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DOI：
10.1007/s12274-023-6017-z
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发表时间：
2023-08
期刊：
影响因子：
9.9
通讯作者：
J. Sui;Mingda Zhao;Zhi-qiang Guo;Jiafeng Li;Jie Chen;Hongli Chen;Jie Liang;Yong Sun;Xingdong Zhang;Yujiang Fan
中科院分区：
文献类型：
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作者：
J. Sui;Mingda Zhao;Zhi-qiang Guo;Jiafeng Li;Jie Chen;Hongli Chen;Jie Liang;Yong Sun;Xingdong Zhang;Yujiang Fan
乳腺癌的局部复发和远处转移仍然是影响患者生存的重要因素。为了解决临床上的挑战，将I型胶原/透明质酸复合体与阿霉素/拉帕替尼纳米粒(Dox/Lap)连接仿生细胞外基质，构建了功能可吸收海绵(HA-SH/PP-Dox/Lap/Col I(HCNPs))。羟基磷灰石海绵具有良好的凝血能力和血液吸收率。值得注意的是，负载Dox/Lap的纳米粒子在降解后同时被赋予了大量的寡聚透明质酸片段，从而增强了对CD44高表达肿瘤细胞的靶向能力。术后4T1模型切除腔内植入羟基喜树碱海绵，通过吸收不可避免的出血，抑制肿瘤细胞散在扩散。更重要的是，具有合适Dox/Lap比例的CD44靶向纳米粒子从海绵中持续释放，杀死周围HCNPs和手术切缘残留的肿瘤细胞，从而防止局部复发和远处转移。因此，功能性羟基磷灰石海绵可能为癌症术后治疗提供一种更安全、更有效的策略。
Locoregional recurrence and distant metastasis of breast cancer still pose a significant risk for patients’ survival. To address the clinical challenge, functional absorbable sponges (HA-SH/PP-Dox/Lap/COL I (HCNPs)) were constructed by biomimetic extracellular matrix of collagen I / hyaluronic acid complex conjugated with doxorubicin/lapatinib (Dox/Lap)-loaded nanoparticles. The HCNPs sponge exhibited excellent clotting ability and blood absorption rate. Worthily, Dox/Lap-loaded nanoparticles were synchronously endowed with a large number of oligo hyaluronic acid segments after degradation, which thus enhanced the ability of targeting into CD44-overexpressed tumor cells. The implantable HCNPs sponge in resected cavity of postoperative 4T1 models inhibited the spread of scattered tumor cells by absorbing the inevitable bleeding. More importantly, CD44 targeted nanoparticle with suitable Dox/Lap proportion continuously released from sponge to kill tumor cells of surrounding HCNPs and those remaining at surgical margin, thus prevented local recurrence as well as distant metastasis. Therefore, the functional HCNPs sponge might provide a safer and more effective strategy for postoperative treatment of cancer.