Chemical modification of bradykinin-polymer conjugates for optimum delivery of nanomedicines to tumors

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2024-03-08 DOI:10.1016/j.nano.2024.102744
Enoch Appiah PhD , Hideaki Nakamura PhD , Anthony Assumang MSc , Tomáš Etrych PhD , Mamoru Haratake PhD
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Abstract

We recently prepared pH-responsive HPMA copolymer conjugates of bradykinin (P-BK), which release BK in response to the acidic tumor microenvironment, and found that administration of P-BK increased the tumor accumulation and therapeutic efficacy of nanomedicine. Because the release of BK from P-BK determines its onset of action, P-BKs with different release rates were prepared, and their properties were evaluated. The release kinetics were significantly altered by substitution proximal to hydrazone bond, release constant of methyl-substituted P-BK (P-MeBK) was approximately 4- and 80-fold higher than that of cyclopropyl-substituted P-BK (P-CPBK) and phenyl-substituted P-BK (P-PhBK). None of the P-BKs were active, but the release of BK restored their BK-like activity. Pre-administration of the P-BKs increased the tumor accumulation of nanomedicine in C26 tumor-bearing mice by 2- and 1.4-fold for P-MeBK and P-PhBK at 3 and 6 h. Altogether, this study provides insights into the design of pH-responsive nanodrugs with the desired release properties to target acidic lesions such as cancer and inflammation.

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对缓激肽-聚合物共轭物进行化学修饰,以优化纳米药物向肿瘤的输送。
我们最近制备了pH响应型缓激肽(P-BK)HPMA共聚物共轭物,这种共轭物会随着肿瘤微环境的酸性而释放缓激肽。由于 BK 从 P-BK 中的释放决定了其起效时间,因此制备了不同释放速率的 P-BK,并对其特性进行了评估。甲基取代的 P-BK(P-MeBK)的释放常数分别是环丙基取代的 P-BK(P-CPBK)和苯基取代的 P-BK(P-PhBK)的 4 倍和 80 倍。这些 P-BK 都没有活性,但释放 BK 后,它们的 BK 样活性得到恢复。总之,这项研究为设计具有理想释放特性的 pH 响应纳米药物提供了启示,使其能够靶向治疗癌症和炎症等酸性病变。
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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