Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles.
Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles.
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与pH依赖性纳米颗粒的化学疗法剂和核酸的递送。
DOI：
10.3390/pharmaceutics15051482
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发表时间：
2023-05-12
期刊：
影响因子：
5.4
通讯作者：
Mixson AJ
中科院分区：
文献类型：
--
作者：
Leng Q;Imtiyaz Z;Woodle MC;Mixson AJ
由于不到百分之一的全身注射纳米粒子在肿瘤中积聚，因此催生了几种新方法来在肿瘤内或肿瘤附近引导和释放治疗。其中一种方法取决于肿瘤细胞外基质和内体的酸性 pH 值。细胞外肿瘤基质的平均 pH 值为 6.8，为 pH 响应颗粒的积累提供梯度，从而实现更高的特异性。被肿瘤细胞摄取后，纳米颗粒进一步暴露于较低的 pH 值，在晚期内涵体中达到 5 的 pH 值。基于肿瘤中的这两种酸性环境，已采用各种pH依赖性靶向策略来从角蛋白或聚合物纳米颗粒等大分子中释放化疗药物或化疗药物与核酸的组合。我们将回顾这些释放策略，包括载体和疏水性化疗剂之间的 pH 敏感连接、聚合物纳米颗粒的质子化和破坏、前两种方法的混合，以及保护载药纳米颗粒的聚合物的释放。虽然一些 pH 敏感策略已在临床前试验中证明了显着的抗肿瘤功效，但许多研究仍处于开发早期，存在一些可能限制其临床使用的障碍。
With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use.
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影响因子：
5
作者：
Alotaibi KM;Almethen AA;Beagan AM;Alfhaid LH;Ahamed M;El-Toni AM;Alswieleh AM
通讯作者：
Alswieleh AM
影响因子：
6.2
作者：
Car, Anja;Baumann, Patric;Meier, Wolfgang
通讯作者：
Meier, Wolfgang
DOI：
10.1016/j.nano.2017.12.010
发表时间：
2018-04-01
影响因子：
5.4
作者：
Charbgoo, Fahimeh;Alibolandi, Mona;Ramezani, Mohammad
通讯作者：
Ramezani, Mohammad
影响因子：
4.7
作者：
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通讯作者：
Gao F
影响因子：
3.7
作者：
Wuang, Shy Chyi;Neoh, Koon Gee;Kang, En-Tang;Leckband, Deborah E.;Pack, Daniel W.
通讯作者：
Pack, Daniel W.