Doxorubicin-Loaded Physalis Mottle Virus Particles as a pH-Responsive Prodrug for Cancer Therapy.,Biotechnology Journal

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Doxorubicin-Loaded Physalis Mottle Virus Particles as a pH-Responsive Prodrug for Cancer Therapy.
Biotechnology Journal ( IF 3.2 ) Pub Date : 2020-09-12 , DOI: 10.1002/biot.202000077
He Hu ₁ , Nicole F Steinmetz _{1,

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Affiliation

The controlled release of drugs using nanoparticle‐based delivery vehicles is a promising strategy to improve the safety and efficacy of chemotherapy. A simple, scalable, and reproducible strategy is developed to synthesize a drug delivery system (DDS) by loading 6‐maleimidocaproyl‐hydrazone doxorubicin (DOX‐EMCH) into the empty core of virus‐like particles (VLPs) derived from Physalis mottle virus (PhMV) via a combination of chemical conjugation to cysteine residues and π–π stacking interactions with the anchored doxorubicin molecule. The DOX‐EMCH prodrug features an acid‐sensitive hydrazine linker that triggers the release of doxorubicin in the slightly acidic extracellular tumor microenvironment or acidic endosomal or lysosomal compartments following cellular uptake. The VLP external surface is coated with polyethylene glycol (PEG) to prevent non‐specific uptake and improve biocompatibility. The DOX‐PhMV‐PEG particles are stable in vitro and show greater efficacy in vivo compared to free doxorubicin in a breast tumor mouse model (using MDA‐MB‐231 cells and nude mice): 92% of the tumor‐bearing mice treated with DOX‐PhMV‐PEG are completely cured compared to 27% of those treated with free doxorubicin under the same conditions, representing a 3.4‐fold improvement. These results lay a foundation for the further development of this biological drug delivery system for a new generation of chemotherapy products.

中文翻译：

负载阿霉素的酸浆斑驳病毒颗粒作为 pH 响应性前药用于癌症治疗。

使用基于纳米颗粒的运载工具控制药物的释放是提高化疗安全性和有效性的一种有前景的策略。开发了一种简单、可扩展且可重复的策略，通过将 6-马来酰亚胺己酰腙阿霉素 (DOX-EMCH) 加载到源自酸浆斑驳病毒 (VLP) 的病毒样颗粒 (VLP) 的空核心中来合成药物递送系统 (DDS)。 PhMV）通过与半胱氨酸残基的化学缀合以及与锚定的阿霉素分子的 π-π 堆积相互作用相结合。 DOX-EMCH 前药具有酸敏感肼连接体，可在细胞摄取后在微酸性细胞外肿瘤微环境或酸性内体或溶酶体区室中触发阿霉素的释放。 VLP 外表面涂有聚乙二醇 (PEG)，以防止非特异性摄取并提高生物相容性。在乳腺肿瘤小鼠模型（使用 MDA-MB-231 细胞和裸鼠）中，DOX-PhMV-PEG 颗粒在体外稳定，并且与游离阿霉素相比在体内显示出更高的功效：92% 的荷瘤小鼠接受了与相同条件下使用游离阿霉素治疗的 27% 的患者相比，DOX-PhMV-PEG 完全治愈，改善了 3.4 倍。这些结果为进一步开发新一代化疗产品的生物给药系统奠定了基础。

更新日期：2020-09-12

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