Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors.
Targeted polymeric nanoparticles for drug delivery to hypoxic, triple-negative breast tumors.
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DOI：
10.1021/acsabm.0c01336
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发表时间：
2021-02-15
影响因子：
4.7
通讯作者：
Mallik S
中科院分区：
文献类型：
--
作者：
Mamnoon B;Loganathan J;Confeld MI;De Fonseka N;Feng L;Froberg J;Choi Y;Tuvin DM;Sathish V;Mallik S
三阴性乳腺癌（triple-negative breast cancer，TNBC）的主要特点是高复发率和重要器官转移。低血管氧分压促进对化疗和放疗的抵抗。神经纤毛蛋白-1（NRP-1）受体在TNBC细胞上高度表达。肿瘤穿透iRGD肽与NRP-1受体相互作用，触发内吞作用和转胞吞作用，并促进穿透。在此，我们合成了一种缺氧响应性的二嵌段PLA-重氮苯-PEG共聚物，并在水性缓冲液中制备了自组装的缺氧响应性聚合物囊泡（Ps）。将iRGD肽掺入聚合物囊泡结构中以制备低氧响应性iRGD缀合的聚合物囊泡（iP）。将多柔比星（DOX）包封在聚合物囊泡中以制备靶向和非靶向低氧响应性聚合物囊泡（分别为DOX-iPs和DOX-Ps）。在常氧条件下（21%氧气），聚合物纳米颗粒在12小时内释放小于30%的其包封的DOX，而在缺氧条件下（2%氧气），多柔比星释放显著增加至超过95%。与常氧相比，靶向聚合物囊泡显著降低了缺氧条件下单层和球状体培养物中TNBC细胞的活力。动物研究显示，靶向聚合物囊泡显著减少异种移植裸鼠中的肿瘤生长。总体而言，靶向聚合物囊泡在TNBC的单层、球状体和动物模型中表现出有效的抗肿瘤活性。随着进一步的发展，这里讨论的靶向纳米载体可能具有作为治疗TNBC的药物载体的转化潜力。
High recurrence and metastasis to vital organs are the major characteristics of triple-negative breast cancer (TNBC). Low vascular oxygen tension promotes resistance to chemo- and radiation therapy. Neuropilin-1 (NRP-1) receptor is highly expressed on TNBC cells. The tumor-penetrating iRGD peptide interacts with the NRP-1 receptor, triggers endocytosis and transcytosis, and facilitates penetration. Herein, we synthesized a hypoxia-responsive diblock PLA–diazobenzene–PEG copolymer and prepared self-assembled hypoxia-responsive polymersomes (Ps) in an aqueous buffer. The iRGD peptide was incorporated into the polymersome structure to make hypoxia-responsive iRGD-conjugated polymersomes (iPs). Doxorubicin (DOX) was encapsulated in the polymersomes to prepare both targeted and non-targeted hypoxia-responsive polymersomes (DOX-iPs and DOX-Ps, respectively). The polymeric nanoparticles released less than 30% of their encapsulated DOX within 12 hours under normoxic conditions (21% oxygen), whereas under hypoxia (2% Oxygen), doxorubicin release remarkably increased to over 95%. The targeted polymersomes significantly decreased TNBC cells’ viability in monolayer and spheroid cultures under hypoxia compared to normoxia. Animal studies displayed that targeted polymersomes significantly diminished tumor growth in xenograft nude mice. Overall, the targeted polymersomes exhibited potent anti-tumor activity in monolayer, spheroid, and animal models of TNBC. With further developments, the targeted nanocarriers discussed here might have the translational potential as drug carriers for the treatment of TNBC.
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DOI：
10.1002/wnan.1343
发表时间：
2015-11
期刊：
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
影响因子：
--
作者：
Miller-Kleinhenz JM;Bozeman EN;Yang L
通讯作者：
Yang L
影响因子：
4.9
作者：
Anajafi, Tayebeh;Yu, Junru;Mallik, Sanku
通讯作者：
Mallik, Sanku
影响因子：
6.2
作者：
Karandish, Fataneh;Mamnoon, Babak;Mallik, Sanku
通讯作者：
Mallik, Sanku
影响因子：
4.9
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
通讯作者：
Mallik S
影响因子：
6.2
作者：
Kulkarni P;Haldar MK;You S;Choi Y;Mallik S
通讯作者：
Mallik S