Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs.
Physalis Mottle Virus-Like Particles as Nanocarriers for Imaging Reagents and Drugs.
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DOI：
10.1021/acs.biomac.7b01196
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发表时间：
2017-12-11
影响因子：
6.2
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Masarapu H;Patel BK;Chariou PL;Hu H;Gulati NM;Carpenter BL;Ghiladi RA;Shukla S;Steinmetz NF
基于植物病毒纳米颗粒(VNPs)和类病毒颗粒(VLP)的平台技术正引起研究人员和临床医生的关注，因为这些颗粒在哺乳动物中具有生物相容性、可生物降解性和非传染性，并且可以很容易地通过化学和基因工程来携带显像剂和药物。当PhMV外壳蛋白在大肠杆菌中表达时，所产生的VLP与体内形成的病毒几乎相同。在这里，我们从ClearColi细胞中分离出PhMV来源的VLP，并分别使用反应性赖氨酸-N-羟基琥珀酰亚胺酯和半胱氨酸-马来酰亚胺化学试剂对荧光团进行外表面和内表面修饰。染料标记颗粒的摄取在一系列癌细胞中进行了测试，并通过共聚焦显微镜和流式细胞术进行了监测。内标于半胱氨酸残基的VLP可被多种癌细胞高效摄取，并在6h内与内切酶标记LAMP-1共定位，而外标于赖氨酸残基的VLP摄取效率较低，这可能反映了细胞表面电荷和结合倾向的差异。将染料和药物分子注入到VLP的空腔中，发现光敏剂(PS)、锌-EPPor和药物结晶紫(MTX)、米托蒽酮(MTX)和阿霉素(DOX)通过非共价相互作用稳定地与载体结合。我们证实了PS-PhMV和DOX-PhMV颗粒对前列腺癌、卵巢癌细胞和乳腺癌细胞的细胞毒作用。我们的结果表明，PhMV衍生的VLP为显像剂和药物的输送提供了一种新的平台技术，并优先摄取到癌细胞中。因此，这些颗粒可以被开发为癌症诊断和治疗的多功能工具。
Platform technologies based on plant virus nano-particles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively. The uptake of dye-labeled particles was tested in a range of cancer cells and monitored by confocal microscopy and flow cytometry. VLPs labeled internally on cysteine residues were taken up with high efficiency by several cancer cell lines and were colocalized with the endolysosomal marker LAMP-1 within 6 h, whereas VLPs labeled externally on lysine residues were taken up with lower efficiency, probably reflecting differences in surface charge and the propensity to bind to the cell surface. The infusion of dye and drug molecules into the cavity of the VLPs revealed that the photosensitizer (PS), Zn-EpPor, and the drugs crystal violet, mitoxantrone (MTX), and doxorubicin (DOX) associated stably with the carrier via noncovalent interactions. We confirmed the cytotoxicity of the PS-PhMV and DOX-PhMV particles against prostate cancer, ovarian and breast cancer cell lines, respectively. Our results show that PhMV-derived VLPs provide a new platform technology for the delivery of imaging agents and drugs, with preferential uptake into cancer cells. These particles could therefore be developed as multifunctional tools for cancer diagnosis and therapy.
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影响因子：
17.1
作者：
Jung, Bongsu;Rao, Ayala L. N.;Anvari, Bahman
通讯作者：
Anvari, Bahman
影响因子：
4.6
作者：
Biabanikhankahdani R;Alitheen NBM;Ho KL;Tan WS
通讯作者：
Tan WS
疫苗开发中的大肠杆菌衍生病毒样颗粒
影响因子：
9.2
作者：
Huang X;Wang X;Zhang J;Xia N;Zhao Q
通讯作者：
Zhao Q
影响因子：
7.8
作者：
Czapar AE;Steinmetz NF
通讯作者：
Steinmetz NF
影响因子：
--
作者：
Gheewala T;Skwor T;Munirathinam G
通讯作者：
Munirathinam G