Nanoparticle pre-treatment for enhancing the survival and activation of pulmonary macrophage transplant.
Nanoparticle pre-treatment for enhancing the survival and activation of pulmonary macrophage transplant.
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DOI：
10.1007/s13346-023-01319-6
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发表时间：
2023-07
影响因子：
5.4
通讯作者：
Fromen, Catherine A.
中科院分区：
文献类型：
--
作者：
Jarai, Bader M.;Bomb, Kartik;Fromen, Catherine A.
尽管最近嵌合抗原受体T细胞疗法在治疗液体癌症方面取得了临床成功，但许多挥之不去的挑战阻碍了治疗转化为更广泛类型的恶性肿瘤。鉴于巨噬细胞在促进肿瘤浸润、获得不同抗原和具有持续刺激适应性反应的能力方面的优势，巨噬细胞已被提议作为T细胞的替代物。然而，除了短暂的抗肿瘤表型状态之外，巨噬细胞在移植后的存活率差一直是阻碍基于巨噬细胞的细胞疗法的主要障碍。鉴于最近发现的纳米颗粒策略在改善巨噬细胞的存活和促进表型保留，我们在此报告的能力，以延长巨噬细胞移植物的存活和表型在小鼠肺通过预处理与不同的降解速率的纳米颗粒。用100 μg/ml剂量的聚（乙二醇）二丙烯酸酯纳米颗粒制剂预处理的巨噬细胞比未处理的细胞提高肺巨噬细胞移植物存活超过7天，其中可降解的纳米颗粒制剂导致相对于未处理的细胞，移植细胞计数的保留增加超过50%。此外，与用经典促炎刺激物干扰素-γ预处理的巨噬细胞相比，预处理的巨噬细胞在移植后7天更有效地保持强加的促炎样极化状态，其中与未处理的对应物相比，在预处理的巨噬细胞移植物中CD 86共刺激分子表达高出大于150%。这些发现为基于巨噬细胞的细胞疗法的寿命和功效的重大改善提供了途径，并对其他基于吞噬细胞的细胞疗法和给药途径具有更广泛的影响。在线版本包含补充材料，可通过10.1007/s13346-023-01319-6获得。
Despite recent clinical successes of chimeric antigen receptor T cell therapies in treating liquid cancers, many lingering challenges stand in the way of therapeutic translation to broader types of malignancies. Macrophages have been proposed as alternatives to T cells given macrophages’ advantages in promoting tumor infiltration, acquiring diverse antigens, and possessing the ability to continuously stimulate adaptive responses. However, the poor survival of macrophages upon transplantation in addition to transient anti-tumor phenotypical states have been major obstacles standing in the way of macrophage-based cell therapies. Given recent discoveries of nanoparticle strategies in improving macrophage survival and promoting phenotype retention, we herein report the ability to extend the survival and phenotype of macrophage transplants in murine lungs via pre-treatment with nanoparticles of varying degradation rates. Macrophages pre-treated with 100 µg/ml dose of poly(ethylene glycol) diacrylate nanoparticle formulations improve pulmonary macrophage transplant survival over untreated cells beyond 7 days, where degradable nanoparticle formulations result in over a 50% increase in retention of transplanted cell counts relative to untreated cells. Furthermore, pre-treated macrophages more efficiently retain an imposed pro-inflammatory-like polarization state following transplantation out to 7 days compared to macrophages pre-treated with a classical pro-inflammatory stimulus, interferon-gamma, where CD86 costimulatory molecule expression is greater than 150% higher in pre-treated macrophage transplants compared to untreated counterparts. These findings provide an avenue for a major improvement in the lifespan and efficacy of macrophage-based cell therapies and have broader implications to other phagocyte-based cellular therapeutics and administration routes. The online version contains supplementary material available at 10.1007/s13346-023-01319-6.
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影响因子：
11.1
作者：
Wang S;Yang Y;Ma P;Zha Y;Zhang J;Lei A;Li N
通讯作者：
Li N
影响因子：
7.5
作者：
Dantuma E;Merchant S;Sugaya K
通讯作者：
Sugaya K
DOI：
10.1016/j.jconrel.2016.07.018
发表时间：
2016-10-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Lee S;Kivimäe S;Dolor A;Szoka FC
通讯作者：
Szoka FC
DOI：
10.1038/s41571-019-0184-6
发表时间：
2019-06
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Shah NN;Fry TJ
通讯作者：
Fry TJ
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H