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A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model

Menghuan Tang,  Kai Lin,  Mythili Ramachandran,  Longmeng Li,  Hongye Zou,  Huzhi Zheng,  Zhao Ma,  Yuanpei Li

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Menghuan Tang, Kai Lin, Mythili Ramachandran, Longmeng Li, Hongye Zou, Huzhi Zheng, Zhao Ma, Yuanpei Li. A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model[J]. 机械工程学报. doi: 10.1016/j.apsb.2022.04.005
引用本文: Menghuan Tang, Kai Lin, Mythili Ramachandran, Longmeng Li, Hongye Zou, Huzhi Zheng, Zhao Ma, Yuanpei Li. A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model[J]. 机械工程学报. doi: 10.1016/j.apsb.2022.04.005
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Menghuan Tang, Kai Lin, Mythili Ramachandran, Longmeng Li, Hongye Zou, Huzhi Zheng, Zhao Ma, Yuanpei Li. A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2022.04.005
Citation: Menghuan Tang, Kai Lin, Mythili Ramachandran, Longmeng Li, Hongye Zou, Huzhi Zheng, Zhao Ma, Yuanpei Li. A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2022.04.005
shu

A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model

doi: 10.1016/j.apsb.2022.04.005

  • a. Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China;

  • b. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA;

  • c. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China;

  • d. College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China

基金项目: 

We thank the support from NIH/NCI (R01CA199668, R01CA232845), NIH/NIDCR (1R01DE029237, USA), NIH/NICHD (R01HD086195, USA), UC Davis Comprehensive Cancer Centre Support Grant (CCSG, USA) awarded by the National Cancer Institute (NCI P30CA093373, USA). Cartoons in Fig. 1 were created with BioRender.com.

详细信息
    通讯作者:

    Zhao Ma,E-mail:mazhao@sdu.edu.cn

    Yuanpei Li,E-mail:lypli@ucdavis.edu

  • 中图分类号: https://www.sciencedirect.com/science/article/pii/S2211383522001757/pdf?md5=c7c0142f989c9c9322ddf9fd96594d35&pid=1-s2.0-S2211383522001757-main.pdf

A mitochondria-targeting lipid–small molecule hybrid nanoparticle for imaging and therapy in an orthotopic glioma model

  • a. Key Laboratory of Luminescent and Real-Time Analytical Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China;

  • b. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA;

  • c. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China;

  • d. College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China

Funds: 

We thank the support from NIH/NCI (R01CA199668, R01CA232845), NIH/NIDCR (1R01DE029237, USA), NIH/NICHD (R01HD086195, USA), UC Davis Comprehensive Cancer Centre Support Grant (CCSG, USA) awarded by the National Cancer Institute (NCI P30CA093373, USA). Cartoons in Fig. 1 were created with BioRender.com.

    摘要
  • 摘要: Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles. Here we developed a kind of lipid-small molecule hybrid nanoparticles (LPHNPs) for imaging and treatment in an orthotopic glioma model. LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate (PQC), a mitochondria-targeting small molecule. Compared with the pure nanofiber self-assembled by PQC, LPHNPs not only preserve the comparable antiproliferative potency, but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection. Also, this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes. By integrating the advantages from liposome and PQC molecule, LPHNPs have minimal system toxicity, enhanced potency of photodynamic therapy (PDT) and visualization capacities of drug biodistribution and tumor imaging. The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma. The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.

     

    Abstract: Hybrid lipid-nanoparticle complexes have shown attractive characteristics as drug carriers due to their integrated advantages from liposomes and nanoparticles. Here we developed a kind of lipid-small molecule hybrid nanoparticles (LPHNPs) for imaging and treatment in an orthotopic glioma model. LPHNPs were prepared by engineering the co-assembly of lipids and an amphiphilic pheophorbide a-quinolinium conjugate (PQC), a mitochondria-targeting small molecule. Compared with the pure nanofiber self-assembled by PQC, LPHNPs not only preserve the comparable antiproliferative potency, but also possess a spherical nanostructure that allows the PQC molecules to be administrated through intravenous injection. Also, this co-assembly remarkably improved the drug-loading capacity and formulation stability against the physical encapsulation using conventional liposomes. By integrating the advantages from liposome and PQC molecule, LPHNPs have minimal system toxicity, enhanced potency of photodynamic therapy (PDT) and visualization capacities of drug biodistribution and tumor imaging. The hybrid nanoparticle demonstrates excellent curative effects to significantly prolong the survival of mice with the orthotopic glioma. The unique co-assembly of lipid and small molecule provides new potential for constructing new liposome-derived nanoformulations and improving cancer treatment.

     

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出版历程
  • 收稿日期:  2021-12-01
  • 修回日期:  2022-03-07
  • 录用日期:  2022-03-31
  • 网络出版日期:  2023-03-17

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