School of Pharmaceutical Science, Shandong University, Jinan 250012,China.
Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan 250012, China.
J Control Release. 2018 Sep 28;286:369-380. doi: 10.1016/j.jconrel.2018.08.011. Epub 2018 Aug 7.
Immunotherapy has exhibited enormous practice in the treatment of melanoma because of the intrinsic properties of tumor. Tumor can downmodulate immune function via multiple mechanisms such as immune checkpoint pathways. The PD-L1 monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells to evade an immune attack, can delay tumor growth efficiently with inevitable disadvantages such as low selectivity and systemic toxicity. Nanomedicine is clearly an approach that holds tremendous potential for addressing the shortcomings and assisting delivery of drugs with proper biodistribution. Herein, we developed a smart nanoplatform with precisely active targeting liposome co-loaded chemotherapy and immunotherapy drugs for synergistic antitumor effects while decreasing systemic toxicity. Immunoliposomes have stable pharmaceutical properties and show a significant antitumor effect in vivo and in vitro. Cellular uptake in vitro and biodistribution in vivo demonstrated that immunoliposomes could be delivered and accumulated more in tumor tissues. These immunoliposomes exhibited effective tumor inhibition and prolonged survival time due to activation of tumor-specific CD8+ T cell and highly selective tumor killing. In addition, safety evaluation of liposomes also demonstrated their increased tumor accumulation and decreased systemic toxicity. Hence, this smart pH-sensitive nanoplatform has promising potential for clinical applications and possibly provides a well-controlled design for combination of chemotherapy with various immunotherapies for further exploration.
免疫疗法在治疗黑色素瘤方面表现出了巨大的潜力,这是由于肿瘤的固有特性。肿瘤可以通过多种机制下调免疫功能,如免疫检查点途径。阻断 PD1/PD-L1 途径的 PD-L1 单克隆抗体诱导肿瘤细胞逃避免疫攻击,虽然可以有效地延缓肿瘤生长,但也不可避免地存在选择性低和全身毒性等缺点。纳米医学显然是一种有潜力的方法,可以解决这些缺点,并有助于药物的适当生物分布。在这里,我们开发了一种具有精确主动靶向脂质体的智能纳米平台,该平台共载化疗药物和免疫治疗药物,以协同抗肿瘤作用,同时降低全身毒性。免疫脂质体具有稳定的药学性质,并在体内和体外显示出显著的抗肿瘤效果。体外细胞摄取和体内生物分布表明,免疫脂质体可以更有效地递送到肿瘤组织并在其中积累。由于激活了肿瘤特异性 CD8+T 细胞和高度选择性的肿瘤杀伤,这些免疫脂质体表现出有效的肿瘤抑制和延长的生存时间。此外,脂质体的安全性评估也表明,它们增加了肿瘤的积累,降低了全身毒性。因此,这种智能 pH 敏感纳米平台具有潜在的临床应用前景,并可能为化疗与各种免疫疗法的联合治疗提供良好的控制设计,以进行进一步的探索。
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