Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-KB signaling in vivo
Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-KB signaling in vivo
复制标题
DOI：
10.1016/j.biomaterials.2023.122096
复制
发表时间：
2023-04-17
期刊：
影响因子：
14
通讯作者：
Liu，Jing
中科院分区：
文献类型：
--
作者：
Xiao，Xiaojuan;Ma，Zekang;Liu，Jing
多发性骨髓瘤（MM）的常规化疗面临着完全缓解率低和转化为复发/难治性的挑战。目前MM一线临床用药硼替佐米（BTZ）面临耐受性增强和不良反应不可忽视的问题。B细胞成熟抗原（BCMA）因其在肿瘤信号传导途径中的重要作用以及嵌合抗原受体T细胞免疫疗法（CAR-T）和抗体药物偶联物（ADC）等新型治疗技术，已被确定为抗MM治疗的理想靶点并受到关注。新兴的纳米技术提供了可行的药物输送方法和新的治疗策略，如光热疗法（PTT）。本论文通过将BTZ、黑磷量子点（BPQDs）、红细胞膜（EM）和BCMA抗体（anti-BCMA）整合在一起，研制了一种以BCMA为靶点的仿生光热纳米微粒BTZ@BPQDs@EM @anti-BCMA（BBE@anti-BCMA）。我们假设，这种工程化的nanomissile可以攻击肿瘤细胞的三重方式，并实现有效的治疗MM。因此，固有的仿生性质的EM和抗BCMA的主动靶向特性增强了治疗药物在肿瘤部位的积累。此外，由于BCMA丰度的降低，显示出潜在的诱变能力。在BPQDs光热效应的支持下，Cleaved-Caspase-3和Bax信号显著增强，Bcl-2表达受到抑制。此外，光热/化疗协同治疗能有效抑制肿瘤生长，逆转NF-κBin的紊乱。更重要的是，这种仿生纳米药物递送系统和抗体诱导的协同治疗策略有效地杀死MM细胞，并且具有可耐受的全身毒性，这是未来临床上抗血液恶性肿瘤的抗癌治疗的有希望的方法。
Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κBin vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.