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多西他赛前药与血卟啉共组装纳米粒用于化疗和光动力治疗的抗肿瘤联合。

Docetaxel prodrug and hematoporphyrin co-assembled nanoparticles for anti-tumor combination of chemotherapy and photodynamic therapy.

机构信息

School of Pharmacy, Shanxi Medical University, Taiyuan, China.

Department of Pharmacy, Shanxi Bethune Hospital, Taiyuan, China.

出版信息

Drug Deliv. 2022 Dec;29(1):3358-3369. doi: 10.1080/10717544.2022.2147280.

DOI:10.1080/10717544.2022.2147280
PMID:36397301
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9848415/
Abstract

To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, anti-tumor activity, pharmacokinetic behavior in rats, distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (HO). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.

摘要

为了实现化疗和光动力疗法的协同抗肿瘤作用，本实验室提供的单硫化修饰的多西紫杉醇（DTX）前药（DSD）和血卟啉（HP）通过纳米沉淀法物理制备共组装纳米粒（DSD/HP NPs）。本研究首次展示了其特征、抗肿瘤活性、在大鼠体内的药代动力学行为、分布以及对 4T1 荷瘤 Balb/c 小鼠的药效学作用。通过单因素和响应面优化优化的 DSD/HP NPs 具有几个明显的特征。首先，它具有深紫色外观，粒径为 105.16±1.24nm，PDI 为 0.168±0.15，DSD/HP NPs 中 DSD 和 HP 的包封效率和载药量分别为 96.27±1.03%和 97.70±0.20%，69.22±1.03%和 20.03±3.12%。其次，它具有良好的稳定性，可以在 pH 7.4 PBS 中以 10mM DTT（HO）的介质中缓慢释放 DTX 和 HP。此外，DSD/HP NPs 联合 NiR 处理显著抑制 4T1 细胞增殖，并诱导更多的活性氧和细胞凋亡。药代动力学和药效学研究表明，DSD/HP NPs 可以延长药物在大鼠体内的循环时间，增加药物在肿瘤部位的分布，明显抑制肿瘤生长，并降低药物对正常组织的暴露。因此，DSD/HP NPs 作为一种有前途的共组装纳米药物递送系统，由于化疗和光动力疗法的结合，有可能提高化疗药物的治疗效率并实现更好的抗肿瘤效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/595cb29d6b9e/IDRD_A_2147280_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/e80bf9dce446/IDRD_A_2147280_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/ca2755b8be23/IDRD_A_2147280_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/4320ba125af6/IDRD_A_2147280_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/55be28e140c3/IDRD_A_2147280_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/6e079bed4a8c/IDRD_A_2147280_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/cdc677363b67/IDRD_A_2147280_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/595cb29d6b9e/IDRD_A_2147280_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/e80bf9dce446/IDRD_A_2147280_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/ca2755b8be23/IDRD_A_2147280_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/4320ba125af6/IDRD_A_2147280_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/55be28e140c3/IDRD_A_2147280_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/6e079bed4a8c/IDRD_A_2147280_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/cdc677363b67/IDRD_A_2147280_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8404/9848415/595cb29d6b9e/IDRD_A_2147280_F0006_C.jpg

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