Synthesis and Characterization of Folic Acid-Functionalized DPLA-co-PEG Nanomicelles for the Targeted Delivery of Letrozole.
Synthesis and Characterization of Folic Acid-Functionalized DPLA-co-PEG Nanomicelles for the Targeted Delivery of Letrozole.
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DOI：
10.1021/acsabm.3c00041
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发表时间：
2023-05-15
影响因子：
4.7
通讯作者：
Bencherif, Sidi A
中科院分区：
文献类型：
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作者：
Rostami, Neda;Gomari, Mohammad Mahmoudi;Abdouss, Majid;Moeinzadeh, Alaa;Choupani, Edris;Davarnejad, Reza;Heidari, Reza;Bencherif, Sidi A
乳腺癌的一种有效治疗方法是使用细胞毒性药物如来曲唑（LTZ）进行化疗。然而，包括LTZ在内的大多数抗癌药物被归类为IV类生物药物，其与低水溶性、低生物利用度和显著毒性相关。因此，开发LTZ的靶向递送系统对于克服这些挑战和限制至关重要。本文以十二醇-聚乳酸-聚乙二醇共聚物（DPLA-co-PEG）为原料制备纳米胶束，采用溶剂乳化蒸发法制备了可生物降解的LSZ纳米载体。此外，癌细胞靶向叶酸（FA）被缀合到纳米胶束中，以实现更有效和更安全的癌症治疗。在我们的研究期间，DPLA-co-PEG和DPLA-co-PEG-FA显示出均匀的球形形态。DPLA-co-PEG和DPLA-co-PEG-FA纳米胶束的平均粒径分别为86.5和241.3 nm。我们的初步数据表明，两种纳米制剂均具有细胞相容性，在所有测试浓度下均具有≥90%的细胞活力。此外，纳米胶束的两亲性导致高载药量和在水中的分散性，导致LTZ的延长释放长达50 h。根据Higuchi模型，用FA官能化的纳米胶束具有将LTZ受控递送到靶细胞中的更大潜力。实验证实了该模型，因为当与游离LTZ和含LTZ的DPLA-co-PEG相比时，含LTZ的DPLA-co-PEG-FA对MCF-7细胞（一种乳腺癌依赖性人乳腺癌细胞系）具有显著且特异性更强的细胞毒性（高达90%的细胞死亡）。此外，当MCF-7细胞暴露于含LTZ的DPLA-co-PEG-FA时，达到87 ± 1 nM的半最大抑制浓度（IC 50），而游离LTZ和含LTZ的DPLA-co-PEG分别需要125 ± 2和100 ± 2 nM的更高剂量。总的来说，DPLA-co-PEG-FA代表了一种有前途的纳米级药物递送系统，以可控地靶向递送药物，如化疗药物。
An effective treatment for hormone-dependent breast cancer is chemotherapy using cytotoxic agents such as letrozole (LTZ). However, most anticancer drugs, including LTZ, are classified as class IV biopharmaceuticals, which are associated with low water solubility, poor bioavailability, and significant toxicity. As a result, developing a targeted delivery system for LTZ is critical for overcoming these challenges and limitations. Here, biodegradable LTZ-loaded nanocarriers were synthesized by solvent emulsification evaporation using nanomicelles prepared with dodecanol-polylactic acid-co-polyethylene glycol (DPLA-co-PEG). Furthermore, cancer cell-targeting folic acid (FA) was conjugated into the nanomicelles to achieve a more effective and safer cancer treatment. During our investigation, DPLA-co-PEG and DPLA-co-PEG-FA displayed a uniform and spherical morphology. The average diameters of DPLA-co-PEG and DPLA-co-PEG-FA nanomicelles were 86.5 and 241.3 nm, respectively. Our preliminary data suggest that both nanoformulations were cytocompatible, with ≥90% cell viability across all concentrations tested. In addition, the amphiphilic nature of the nanomicelles led to high drug loading and dispersion in water, resulting in the extended release of LTZ for up to 50 h. According to the Higuchi model, nanomicelles functionalized with FA have a greater potential for the controlled delivery of LTZ into target cells. This model was confirmed experimentally, as LTZ-containing DPLA-co-PEG-FA was significantly and specifically more cytotoxic (up to 90% cell death) toward MCF-7 cells, a hormone-dependent human breast cancer cell line, when compared to free LTZ and LTZ-containing DPLA-co-PEG. Furthermore, a half-maximal inhibitory concentration (IC50) of 87 ± 1 nM was achieved when MCF-7 cells were exposed to LTZ-containing DPLA-co-PEG-FA, whereas higher doses of 125 ± 2 and 100 ± 2 nM were required for free LTZ and LTZ-containing DPLA-co-PEG, respectively. Collectively, DPLA-co-PEG-FA represents a promising nanosized drug delivery system to target controllably the delivery of drugs such as chemotherapeutics.
影响因子：
4.7
作者：
通讯作者：
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影响因子：
3.9
作者：
通讯作者：
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