Purpose

Gold porphyrin (AuP) is a complex that has been shown to be potent against various tumors. A biocompatible interpenetrating network (IPN) system comprised of polyethyleneglycol diacrylate (PEGdA) and chemically-modified gelatin has been shown to be an effective implantable drug depot to deliver AuP locally. Here we designed IPN microparticles complexed with AuP to facilitate intravenous administration and to diminish systemic toxicity.

Methods

We have synthesized and optimized an IPN microparticle formulation complexed with AuP. Tumor cell cytotoxicity, antitumor activity, and survival rate in lung cancer bearing nude mice were analyzed.

Results

IPN microparticles maintained AuP bioactivity against lung cancer cells (NCI-H460). In vivo study showed no observable systemic toxicity in nude mice bearing NCI-H460 xenografts after intravenous injection of 6 mg/kg AuP formulated with IPN microparticles. An anti-tumor activity level comparable to free AuP was maintained. Mice treated with 6 mg/kg AuP in IPN microparticles showed 100% survival rate while the survival rate of mice treated with free AuP was much less. Furthermore, microparticle-formulated AuP significantly reduced the intratumoral microvasculature when compared with the control.

Conclusion

AuP in IPN microparticles can reduce the systemic toxicity of AuP without compromising its antitumor activity. This work highlighted the potential application of AuP in IPN microparticles for anticancer chemotherapy.

中文翻译：

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掺有金化合物的多功能微粒抑制人肺癌异种移植。

目的

卟啉金（AuP）是一种复合物，已证明对多种肿瘤有效。由聚乙二醇二丙烯酸酯（PEGdA）和化学修饰的明胶组成的生物相容性互穿网络（IPN）系统已被证明是一种有效的可植入药物储库，可以局部递送AuP。在这里，我们设计了与AuP配合使用的IPN微粒，以促进静脉内给药并降低全身毒性。

方法

我们已经合成并优化了与AuP复合的IPN微粒配方。分析了荷瘤裸鼠中肿瘤细胞的细胞毒性，抗肿瘤活性和存活率。

结果

IPN微粒保持了针对肺癌细胞（NCI-H460）的AuP生物活性。体内研究表明，在静脉注射6 mg / kg用IPN微粒配制的AuP后，在携带NCI-H460异种移植物的裸鼠中没有观察到的全身毒性。维持了与游离AuP相当的抗肿瘤活性水平。IPN微粒中6 mg / kg AuP处理的小鼠显示100％的存活率，而游离AuP处理的小鼠的存活率要低得多。此外，与对照相比，微粒配制的AuP显着降低了肿瘤内微脉管系统。

结论

IPN微粒中的AuP可以降低AuP的全身毒性，而不会损害其抗肿瘤活性。这项工作强调了AuP在IPN微粒中用于抗癌化学疗法的潜在应用。