Mucoadhesive-to-penetrating controllable peptosomes-in-microspheres co-loaded with anti-miR-31 oligonucleotide and Curcumin for targeted colorectal cancer therapy
Mucoadhesive-to-penetrating controllable peptosomes-in-microspheres co-loaded with anti-miR-31 oligonucleotide and Curcumin for targeted colorectal cancer therapy
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粘膜粘附渗透性可控微球蛋白体共载抗 miR-31 寡核苷酸和姜黄素用于靶向结直肠癌治疗
DOI：
10.7150/thno.40318
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发表时间：
2020-02
期刊：
影响因子：
12.4
通讯作者：
Yu Zhengquan
中科院分区：
文献类型：
--
作者：
Zhao Ran;Du Sujuan;Liu Ying;Lv Cong;Song Yongli;Chen Xinchun;Zhang Bing;Li Dan;Gao Shan;Cui Wei;Plikus Maksim V;Hou Xiaohua;Wu Kaichun;Liu Zhanju;Liu Zhihua;Cong Yingzi;Li Yuan;Yu Zhengquan
背景：越来越多的证据表明，纳米药物大大降低了结直肠癌的副作用，提高了治疗效果。特别是，目前正在出现使用直肠给药的纳米药物，其优点是治疗效果快，肝脏首过效应逐渐减弱。方法：建立结直肠癌靶向递送系统，将α-乳清蛋白肽体（ps）与microRNA -31抑制剂（miR-31i）和姜黄素（Cur）包被在硫代TEMPO氧化魔芋葡甘聚糖（sOKGM）微球（sOKGM - ps -miR-31i/Cur）中。在结直肠癌细胞和偶氮甲烷-葡聚糖钠（AOM-DSS）诱导的肿瘤模型中评估sOKGM-PS-miR-31i/Cur递送系统的CRC靶向能力、药物释放谱、黏附-穿透特性和治疗效果。结果：经直肠或口服给药后，sOKGM-PS-miR-31i/Cur给药系统在恶劣的胃肠道环境中稳定；由于二硫键与结肠黏液层的相互作用，它们也具有黏附性，从而增强了药物在结肠中的保留和局部生物利用度。同时，从微球中释放出的PS-miR-31i/Cur ps具有穿透黏液的特性，能够有效地穿过结肠黏液层，使得Cur和miR-31i在CD133靶向肽的引导下特异性靶向结肠肿瘤细胞。因此，在偶氮甲烷-葡聚糖硫酸钠（AOM-DSS）诱导的肿瘤模型中，直肠递送sOKGM-PS-miR-31i/Cur微球可抑制肿瘤生长。结论：sOKGM-PS-miR-31i/Cur微球是一种有效的直肠给药系统，具有黏附性和穿透性双重优点，是一种有效可行的结直肠癌治疗方法。
Background: Accumulating evidences indicate that nanomedicines greatly decrease the side effects and enhance the efficacy of colorectal cancer (CRC) treatment. In particular, the use of rectal delivery of nanomedicines, with advantages such as fast therapeutic effects and a diminishing hepatic first-pass effect, is currently emerging. Method: We established a CRC targeted delivery system, in which α-lactalbumin peptosomes (PSs) co-loaded with a microRNA (miR)-31 inhibitor (miR-31i) and curcumin (Cur) were encapsuslated in thiolated TEMPO oxidized Konjac glucomannan (sOKGM) microspheres, referred as sOKGM-PS-miR-31i/Cur. The CRC targeting capability, drug release profiles, mucoadhesive-to-penetrating properties and therapeutic efficacy of sOKGM-PS-miR-31i/Cur delivery system were evaluated in colorectal cancer cells and azoxymethane-dextran sodium (AOM-DSS) induced tumor models. Results: sOKGM-PS-miR-31i/Cur delivery system were stable in the harsh gastrointestinal environment after rectal or oral administration; and were also mucoadhesive due to disulfide bond interactions with the colonic mucus layer, resulting in an enhanced drug retention and local bioavailability in the colon. Concomitantly, the released PS-miR-31i/Cur PSs from the microsphere was mucus-penetrating, efficiently passing through the colonic mucus layer, and allowed Cur and miR-31i specifically target to colon tumor cells with the guide of CD133 targeting peptides. Consequently, rectal delivery of sOKGM-PS-miR-31i/Cur microspheres suppressed tumor growth in an azoxymethane-dextran sodium sulfate (AOM-DSS)-induced tumor model. Conclusion: sOKGM-PS-miR-31i/Cur microspheres are effective rectal delivery system with combined advantages of mucoadhesive and mucus-penetrating properties, representing a potent and viable therapeutic approach for CRC.
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