Light-Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo-, Antiangiogenic, and Anti-MDSC Therapy in Melanoma
Light-Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo-, Antiangiogenic, and Anti-MDSC Therapy in Melanoma
复制标题
仿生纳米系统的光触发高效顺序药物输送，用于黑色素瘤的多模式化疗、抗血管生成和抗 MDSC 治疗
DOI：
10.1002/adma.202106682
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发表时间：
2022-01-31
影响因子：
29.4
通讯作者：
Fang, Chao
中科院分区：
文献类型：
--
作者：
Lai, Xing;Liu, Xue-Liang;Fang, Chao
鉴于肿瘤的多种病理特征，需要用于顺序递送靶标分别位于肿瘤细胞内部和外部的各种药物的纳米系统来改善癌症治疗。然而，目前的顺序递送主要是通过纳米载体的酶或酸依赖性降解来实现，这会受到异质肿瘤微环境的影响，药物作用于肿瘤细胞外靶点的卸载效率通常不理想。在这里，开发了一种基于水腔中负载阿霉素（DOX）的小尺寸聚合物纳米颗粒（DOX-NP）和游离舒尼替尼的脂质体制剂的光触发顺序递送策略。脂质体膜掺杂光敏剂卟啉磷脂（PoP）并与红细胞膜杂交以赋予仿生特征。近红外光诱导的膜透化触发舒尼替尼的“超快”和“彻底”释放（5 分钟内 100% 释放），用于抗血管生成治疗以及骨髓源性抑制细胞 (MDSC) 抑制，以逆转免疫抑制肿瘤环境。随后，从脂质体中释放的小尺寸 DOX-NP 更容易被肿瘤细胞摄取，以改善免疫原性化疗。 RNA 测序和免疫相关测定表明治疗性免疫增强。这种光触发的顺序递送策略证明了癌症多模式治疗针对肿瘤微环境中不同空间位置的多个靶标的效力。
In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme- or acid-dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light-triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)-loaded small-sized polymeric nanoparticles (DOX-NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin-phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near-infrared light-induced membrane permeabilization triggers the "ultrafast" and "thorough" release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid-derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small-sized DOX-NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune-related assay indicates therapeutic immune enhancement. This light-triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.