Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors.
Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors.
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DOI：
10.1021/acs.molpharmaceut.0c00247
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发表时间：
2020-08-03
影响因子：
4.9
通讯作者：
Mallik S
中科院分区：
文献类型：
--
作者：
Confeld MI;Mamnoon B;Feng L;Jensen-Smith H;Ray P;Froberg J;Kim J;Hollingsworth MA;Quadir M;Choi Y;Mallik S
在胰腺导管腺癌（PDAC）中，早期缺氧触发细胞外基质重塑、上皮向间质转化、细胞存活增加、癌症干细胞形成和耐药。PDAC中的缺氧还与富含胶原的纤维细胞外基质（结缔组织增生）的发展有关，导致药物渗透严重受损。为了克服这些艰巨的挑战，我们创造了聚合物纳米颗粒（聚合体），它可以靶向并穿透胰腺肿瘤，到达缺氧壁龛，经历快速的结构不稳定，并释放被封装的药物。体外研究表明，与未封装的药物相比，在缺氧条件下，多聚体的细胞摄取高，药物的细胞毒性增加。与未经治疗的对照组相比，聚合体使小鼠肿瘤生长减少了近250%，肿瘤内坏死明显增加了60%。我们预计这些聚合物纳米颗粒在向实体缺氧肿瘤输送药物方面具有相当大的转化潜力。
In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely-impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In-vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to unencapsulated drugs. The polymersomes decreased tumor growth by nearly 250% and significantly increased necrosis within the tumors by 60% in mice compared to untreated controls. We anticipate that these polymer nanoparticles possess considerable translational potential for delivering drugs to solid hypoxic tumors.
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影响因子：
8.8
作者：
Akashi, Y.;Oda, T.;Ohara, Y.;Miyamoto, R.;Kurokawa, T.;Hashimoto, S.;Enomoto, T.;Yamada, K.;Satake, M.;Ohkohchi, N.
通讯作者：
Ohkohchi, N.
影响因子：
4.9
作者：
Anajafi, Tayebeh;Yu, Junru;Mallik, Sanku
通讯作者：
Mallik, Sanku
影响因子：
5.7
作者：
HOCKEL, M;KNOOP, C;VAUPEL, P
通讯作者：
VAUPEL, P
影响因子：
11.5
作者：
Fukahi, K;Fukasawa, M;Korc, M
通讯作者：
Korc, M
DOI：
10.1007/978-981-10-6728-0_24
发表时间：
2017-01-01
期刊：
ROLE OF TRANSCRIPTION FACTORS IN GASTROINTESTINAL MALIGNANCIES
影响因子：
--
作者：
Daddacha, Waaqo B.;Koyen, Allyson E.;Yu, David S.
通讯作者：
Yu, David S.