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温度响应性聚合物修饰脂质体的可调表面性质促进更快的细胞摄取。

Tunable Surface Properties of Temperature-Responsive Polymer-Modified Liposomes Induce Faster Cellular Uptake.

作者信息

Wang Jian, Ayano Eri, Maitani Yoshie, Kanazawa Hideko

机构信息

Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512, Japan.

出版信息

ACS Omega. 2017 Jan 31;2(1):316-325. doi: 10.1021/acsomega.6b00342.

DOI:10.1021/acsomega.6b00342
PMID:31457232
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6640984/
Abstract

Drug delivery by nanoparticle carriers has been limited by inefficient intracellular drug delivery. Temperature-responsive poly(-isopropylacrylamide) (PNIPAAm)-modified liposomes can release their content following heating. In this study, we synthesized the temperature-responsive polymer poly(-isopropylacrylamide)--,'-dimethylaminopropylacrylamide (P(NIPAAm--DMAPAAm)) and investigated the properties of liposomes modified with P(NIPAAm--DMAPAAm) for intracellular drug carriers. The copolymer displayed a thermosensitive transition at a lower critical solution temperature (LCST) that is higher than body temperature. Above the LCST, the temperature-responsive liposomes started to aggregate and release. The liposomes showed a fixed aqueous layer thickness (FALT) at the surface below the LCST, and the FALT decreased with increasing temperature. Above 37 °C, cytosolic release from the temperature-responsive liposomes was higher than that from the PEGylated liposomes, indicating intracellular uptake. Here, we showed that the tunable surface properties of the temperature-responsive polymer-modified liposomes possibly enabled their dehydration by heating, which likely induced a faster cellular uptake and release. Therefore, the liposomes could be highly applicable for improving intracellular drug-delivery carriers.

摘要

纳米颗粒载体的药物递送受到细胞内药物递送效率低下的限制。温度响应性聚（N-异丙基丙烯酰胺）（PNIPAAm）修饰的脂质体在加热后可以释放其内容物。在本研究中，我们合成了温度响应性聚合物聚（N-异丙基丙烯酰胺-co-N，N'-二甲基氨丙基丙烯酰胺）（P（NIPAAm-co-DMAPAAm）），并研究了用P（NIPAAm-co-DMAPAAm）修饰的脂质体作为细胞内药物载体的性质。该共聚物在高于体温的较低临界溶液温度（LCST）下表现出热敏转变。高于LCST时，温度响应性脂质体开始聚集并释放。在LCST以下，脂质体表面显示出固定的水层厚度（FALT），并且FALT随温度升高而降低。在37°C以上，温度响应性脂质体的胞质释放高于聚乙二醇化脂质体，表明其被细胞摄取。在这里，我们表明温度响应性聚合物修饰的脂质体的可调表面性质可能使其通过加热脱水，这可能导致更快的细胞摄取和释放。因此，这些脂质体在改善细胞内药物递送载体方面具有高度适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/18d51478429b/ao-2016-00342b_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/55666739d82d/ao-2016-00342b_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/f897f8eecf7c/ao-2016-00342b_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/eb144e6cf957/ao-2016-00342b_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/d1a362616fad/ao-2016-00342b_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/44d5a5e17dad/ao-2016-00342b_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/a9f2e11e0921/ao-2016-00342b_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/f259fa22f888/ao-2016-00342b_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/55273376d181/ao-2016-00342b_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/8d3326c0a939/ao-2016-00342b_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/18d51478429b/ao-2016-00342b_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/55666739d82d/ao-2016-00342b_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/f897f8eecf7c/ao-2016-00342b_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/eb144e6cf957/ao-2016-00342b_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/d1a362616fad/ao-2016-00342b_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/44d5a5e17dad/ao-2016-00342b_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/a9f2e11e0921/ao-2016-00342b_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/f259fa22f888/ao-2016-00342b_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/55273376d181/ao-2016-00342b_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/8d3326c0a939/ao-2016-00342b_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2fa/6640984/18d51478429b/ao-2016-00342b_0010.jpg

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