School of Chemical and Biological Engineering , Seoul National University , Seoul 08826 , Republic of Korea.
Interdisciplinary Program of Bioengineering , Seoul National University , Seoul 08826 , Republic of Korea.
Nano Lett. 2019 Aug 14;19(8):5185-5193. doi: 10.1021/acs.nanolett.9b01571. Epub 2019 Jul 16.
Liposomes are clinically used as drug carriers for cancer therapy; however, unwanted leakage of the encapsulated anticancer drug and poor tumor-targeting efficiency of liposomes may generate toxic side effects on healthy cells and lead to failure of tumor eradication. To overcome these limitations, we functionalized liposomes with a photosensitizer (KillerRed, KR)-embedded cancer cell membrane (CCM). A lipid adjuvant was also embedded in the lipocomplex to promote the anticancer immune response. KR proteins were expressed on CCM and did not leak from the lipocomplex. Owing to the homotypic affinity of the CCM for the source cancer cells, the lipocomplex exhibited a 3.3-fold higher cancer-targeting efficiency than a control liposome. The liposome functionalized with KR-embedded CCM and lipid adjuvant generated cytotoxic reactive oxygen species in photodynamic therapy and effectively induced anticancer immune responses, inhibiting primary tumor growth and lung metastasis in homotypic tumor-bearing mice. Taken together, the lipocomplex technology may improve liposome-based cancer therapy.
脂质体临床上被用作癌症治疗的药物载体;然而,包裹的抗癌药物的意外泄漏和脂质体对肿瘤的靶向效率差可能会对健康细胞产生毒性副作用,并导致肿瘤无法根除。为了克服这些限制,我们用光敏剂(KillerRed,KR)嵌入的癌细胞膜(CCM)对脂质体进行功能化。脂质佐剂也被嵌入脂质复合物中以促进抗癌免疫反应。KR 蛋白在 CCM 上表达,不会从脂质复合物中泄漏。由于 CCM 与源癌细胞的同型亲和力,脂质复合物对癌症的靶向效率比对照脂质体高 3.3 倍。用 KR 嵌入的 CCM 和脂质佐剂功能化的脂质体在光动力治疗中产生细胞毒性活性氧,有效地诱导抗癌免疫反应,抑制同源荷瘤小鼠的原发性肿瘤生长和肺转移。总之,脂质复合物技术可以改善基于脂质体的癌症治疗。