Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, 58105, USA.
Department of Animal and Range Sciences, North Dakota State University, Fargo, North Dakota, 58105, USA.
Chemistry. 2018 Aug 27;24(48):12490-12494. doi: 10.1002/chem.201802229. Epub 2018 Jul 30.
Hypoxia in solid tumors facilitates the progression of the disease, develops resistance to chemo and radiotherapy, and contributes to relapse. Due to the lack of tumor penetration, most of the reported drug carriers are unable to reach the hypoxic niches of the solid tumors. We have developed tissue-penetrating, hypoxia-responsive echogenic polymersomes to deliver anticancer drugs to solid tumors. The polymersomes are composed of a hypoxia-responsive azobenzene conjugated and a tissue penetrating peptide functionalized polylactic acid-polyethylene glycol polymer. The drug-encapsulated, hypoxia-responsive polymersomes substantially decreased the viability of pancreatic cancer cells in spheroidal cultures. Under normoxic conditions, polymersomes were echogenic at diagnostic ultrasound frequencies but lose the echogenicity under hypoxia. In-vivo imaging studies with xenograft mouse model further confirmed the ability of the polymersomes to target, penetrate, and deliver the encapsulated contents in hypoxic pancreatic tumor tissues.
肿瘤缺氧会促进疾病进展，使化疗和放疗产生耐药性，并导致肿瘤复发。由于缺乏对肿瘤的穿透性，大多数已报道的药物载体都无法到达实体瘤的缺氧部位。我们开发了组织穿透性、缺氧响应性声敏聚合物囊泡来向实体瘤递送抗癌药物。这些聚合物囊泡由缺氧响应性偶氮苯共轭物和组织穿透肽功能化的聚乳酸-聚乙二醇聚合物组成。包载药物的缺氧响应性聚合物囊泡显著降低了球体培养中胰腺癌细胞的活力。在常氧条件下，聚合物囊泡在诊断超声频率下具有声敏性，但在缺氧下失去声敏性。在异种移植小鼠模型的体内成像研究中进一步证实了聚合物囊泡能够靶向、穿透并递送到缺氧胰腺肿瘤组织中的囊封内容物。
