(131)I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors.
(131)I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors.
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131I 标记的多功能聚乙烯亚胺/阿霉素复合物具有 pH 控制的细胞摄取特性，可增强肿瘤的 SPECT 成像和化疗/放射治疗
DOI：
10.2147/ijn.s312238
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发表时间：
2021
影响因子：
8
通讯作者：
Miao W
中科院分区：
文献类型：
--
作者：
Zhu J;Yang J;Zhao L;Zhao P;Yang J;Zhao J;Miao W
智能治疗诊断纳米系统具有良好的潜力，以提高肿瘤内的内化，同时避免与正常组织的非特异性相互作用。然而，开发这种类型的治疗诊断纳米系统仍然是一个挑战。方法本研究开发了碘-131（131 I）标记的多功能聚乙烯亚胺（PEI）/多柔比星（DOX）复合物，该复合物具有pH控制的细胞摄取特性，可用于肿瘤的单光子发射计算机断层扫描（SPECT）增强成像和化疗/放疗。利用烷氧基苯基酰基磺酰胺（APAS）的巯基和MAL-PEG-SVA的MAL部分，将其与用具有单甲醚和N-羟基琥珀酰亚胺端基的聚乙二醇（PEG）（mPEG-NHS）、具有马来酰亚胺和琥珀酰亚胺戊酸酯端基的PEG（MAL-PEG-SVA）预修饰的功能PEI缀合。随后与3-（4 '-羟基苯基）丙酸-OSu（HPAO）缀合，乙酰化PEI的剩余胺，络合DOX并标记131 I以产生治疗诊断纳米系统。结果合成的纳米诊断治疗系统具有良好的水溶性和稳定性。每个功能性PEI可复合约12.4个DOX，并能以pH依赖性方式持续释放DOX。值得注意的是，由于APAS的表面修饰，所构建的治疗诊断纳米系统具有实现pH响应性电荷转换的能力，并进一步导致在微酸性条件下癌细胞中细胞摄取的改善。基于DOX和放射性131 I在单一纳米系统中的共存，所合成的纳米杂化系统可以在体外提供增强的SPECT成像以及癌细胞和异种移植肿瘤模型的体内化疗/放射性联合治疗。讨论所开发的智能纳米混合系统提供了一种新的策略，以提高肿瘤治疗诊断效率，并可应用于不同类型的癌症。
Introduction Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge. Methods In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4’-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems. Results The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sustainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo. Discussion The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.