Doxorubicin-Loaded Physalis Mottle Virus Particles Function as a pH-Responsive Prodrug Enabling Cancer Therapy.
Doxorubicin-Loaded Physalis Mottle Virus Particles Function as a pH-Responsive Prodrug Enabling Cancer Therapy.
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DOI：
10.1002/biot.202000077
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发表时间：
2020-12
影响因子：
4.7
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Hu H;Steinmetz NF
利用纳米粒为载体的药物控制释放是提高化疗安全性和有效性的一种有前途的策略。我们开发了一种简单、可扩展和可重复性的策略来合成药物传递系统，方法是通过半胱氨酸残基的化学结合和π-π与锚定的阿霉素分子的堆积作用，将前药6-马来酰亚胺卡丙基-酰肼阿霉素(DOX-EMCH)装载到来源于PHMV的病毒样颗粒(VLP)的空核中。DOX-Emch前药的特点是一种对酸敏感的肼连接物，它能在细胞摄取后在微酸性的细胞外肿瘤微环境或酸性的内体或溶酶体室中触发阿霉素的释放。在VLP外表面涂覆聚乙二醇膜，以防止非特异性摄取，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颗粒在体外是稳定的，在体内表现出明显比游离阿霉素更好的疗效：在相同条件下，DOX-PhMV-PEG治疗荷瘤小鼠的完全治愈率为92%，而游离阿霉素治疗的完全治愈率为27%，提高了3.4倍。这些结果为进一步开发用于新一代化疗产品的生物给药系统奠定了基础。以酸浆斑驳病毒(PhMV)为载体，以6-马来酰亚胺基硫脲阿霉素(DOX-PhMV-PEG)为载体，制备了pH响应型药物释放系统(DDS)。在乳腺肿瘤小鼠模型中，与游离阿霉素相比，DDS的体内疗效显著提高：在相同条件下，接受DOX-PhMV-PEG治疗的荷瘤小鼠完全治愈的比例为92%，而接受游离阿霉素治疗的小鼠完全治愈的比例为27%，提高了3.4倍。
The controlled release of drugs using nanoparticle-based delivery vehicles is a promising strategy to improve the safety and efficacy of chemotherapy. We have developed a simple, scalable, and reproducible strategy to synthesize a drug delivery system by loading the prodrug 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 was coated with polyethylene glycol (PEG) to prevent non-specific uptake and improve biocompatibility. The DOX-PhMV-PEG particles were stable in vitro and showed significantly 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 were 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 our biological drug delivery system for a new generation of chemotherapy products. The authors developed a pH-responsive drug delivery system (DDS) based on virus-like particles derived from Physalis mottle virus (PhMV) loaded with 6-maleimidocaproyl-hydrazone doxorubicin (DOX-PhMV-PEG). The DDS demonstrated significantly greater efficacy in vivo compared to free doxorubicin in a breast tumor mouse model: 92% of the tumor-bearing mice treated with DOX-PhMV-PEG were completely cured compared to 27% of those treated with free doxorubicin under the same conditions, representing a 3.4-fold improvement.
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影响因子：
4.9
作者：
Franke, Christina E.;Czapar, Anna E.;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.
基于病毒的纳米材料的设计，用于医学，生物技术和能量。
影响因子：
46.2
作者：
Wen AM;Steinmetz NF
通讯作者：
Steinmetz NF
影响因子：
6.6
作者：
Lam, Patricia;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.
影响因子：
6.2
作者：
Masarapu H;Patel BK;Chariou PL;Hu H;Gulati NM;Carpenter BL;Ghiladi RA;Shukla S;Steinmetz NF
通讯作者：
Steinmetz NF
影响因子：
6.2
作者：
Rifkin, RM;Gregory, SA;Hussein, MA
通讯作者：
Hussein, MA