Engineered a dual-targeting biomimetic nanomedicine for pancreatic cancer chemoimmunotherapy.
Engineered a dual-targeting biomimetic nanomedicine for pancreatic cancer chemoimmunotherapy.
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DOI：
10.1186/s12951-022-01282-3
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发表时间：
2022-02-17
影响因子：
10.2
通讯作者：
Liang T
中科院分区：
文献类型：
--
作者：
Wang M;Hu Q;Huang J;Zhao X;Shao S;Zhang F;Yao Z;Ping Y;Liang T
免疫抑制的肿瘤微环境使吉西他滨等化疗药物对胰腺癌的治疗作用明显减弱。通过靶向肿瘤相关巨噬细胞和重组肿瘤微环境以增强其疗效来提高化疗效果可能成为一种有前途的策略。为此，我们开发了一种仿生双靶向纳米药物(PG@KMCM)，其中载吉西他滨的聚(乳酸-乙醇酸)(PLGA)纳米粒子被一层生物工程癌细胞膜覆盖，该细胞膜稳定表达针对M2样巨噬细胞(M2pep)的多肽，同时保留肿瘤相关抗原(TAAs)。PG@KMCM纳米药物使吉西他滨同时定向输送到胰腺肿瘤部位和TAMs，以增强其治疗效果。此外，免疫检查点抑制剂(PD-L1抗体)与PG@KMCM的结合通过对免疫抑制的肿瘤微环境进行重新编程，包括消除PD-L1阳性的巨噬细胞和下调PD-L1的表达，协同增强了抗肿瘤效果。我们的研究证明，双靶向PG@KMCM纳米药物与PD-L1免疫检查点抑制剂联合治疗能够有效地重新编程肿瘤微环境，杀死胰腺癌细胞，从而提高整体治疗潜力。网上版载有补充材料，可在10.1186/s12951-022-01282-3查阅。
The therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To this end, we developed a biomimetic dual-targeting nanomedicine (PG@KMCM) where gemcitabine-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles are coated with a layer of bioengineered cancer cell membrane that stably expresses peptides targeting M2-like macrophages (M2pep) while reserving tumor-associated antigens (TAAs). The PG@KMCM nanomedicine enables the simultaneous targeted delivery of gemcitabine to pancreatic tumor sites and TAMs to potentiate its therapeutic effects. Furthermore, the combination of an immune checkpoint inhibitor (PD-L1 antibody) with PG@KMCM synergistically enhanced the anti-tumoral effect by reprogramming the immune-suppressive tumor microenvironment, including the elimination of PD-L1-positive macrophages and the downregulation of PD-L1 expression. Our study proved dual-targeting PG@KMCM nanomedicine in combination with PD-L1 immune checkpoint inhibitor therapy is able to effectively reprogram the tumor microenvironment and kill pancreatic cancer cells to enhance overall therapeutic potential. The online version contains supplementary material available at 10.1186/s12951-022-01282-3.
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PD-1/PD-L1检查点激活需要髓样细胞，并在胰腺癌中建立免疫抑制环境。
影响因子：
24.5
作者：
Zhang Y;Velez-Delgado A;Mathew E;Li D;Mendez FM;Flannagan K;Rhim AD;Simeone DM;Beatty GL;Pasca di Magliano M
通讯作者：
Pasca di Magliano M
影响因子：
16.6
作者：
Xue J;Sharma V;Hsieh MH;Chawla A;Murali R;Pandol SJ;Habtezion A
通讯作者：
Habtezion A
DOI：
10.1073/pnas.1312197110
发表时间：
2013-10-01
影响因子：
11.1
作者：
Cieslewicz, Maryelise;Tang, Jingjing;Pun, Suzie H.
通讯作者：
Pun, Suzie H.
影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
影响因子：
5
作者：
Bulle, Ashenafi;Dekervel, Jeroen;van Pelt, Jos
通讯作者：
van Pelt, Jos