• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2020
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles 2020
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Liang, B.J.
    Pigula, M.
    Huang, H.-C.
    Date
    2020
    Journal
    Journal of Nanobiotechnology
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1186/s12951-019-0560-5
    Abstract
    Background: Photoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing. The trade-off between PIC selectivity and PIC uptake is a major drawback limiting the efficacy of photoimmunotherapy. Despite ample evidence showing that photoimmunotherapy is most effective when combined with chemotherapy, the design of nanocarriers to co-deliver PICs and chemotherapy drugs remains an unmet need. To overcome these challenges, we developed a novel photoimmunoconjugate-nanoliposome (PIC-Nal) comprising of three clinically used agents: anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab (Cet), benzoporphyrin derivative (BPD) photosensitizer, and irinotecan (IRI) chemotherapy. Results: The BPD photosensitizers were first tethered to Cet at a molar ratio of 6:1 using carbodiimide chemistry to form PICs. Conjugation of PICs onto nanoliposome irinotecan (Nal–IRI) was facilitated by copper-free click chemistry, which resulted in monodispersed PIC–Nal–IRI with an average size of 158.8 ± 15.6 nm. PIC–Nal–IRI is highly selective against EGFR-overexpressing epithelial ovarian cancer cells with 2- to 6-fold less accumulation in low EGFR expressing cells. Successful coupling of PIC onto Nal–IRI enhanced PIC uptake and photoimmunotherapy efficacy by up to 30% in OVCAR-5 cells. Furthermore, PIC–Nal–IRI synergistically reduced cancer viability via a unique three-way mechanism (i.e., EGFR downregulation, mitochondrial depolarization, and DNA damage). Conclusion: It is increasingly evident that the most effective therapies for cancer will involve combination treatments that target multiple non-overlapping pathways while minimizing side effects. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. PIC–Nal–IRI offers a promising strategy to overcome the selectivity-uptake trade-off, improve photoimmunotherapy efficacy, and enable multi-tier cancer targeting. Controllable drug compartmentalization, easy surface modification, and high clinical relevance collectively make PIC–Nal–IRI extremely valuable and merits further investigations in living animals. Copyright 2020 The Author(s).
    Keyword
    Benzoporphyrin derivative
    Epidermal growth factor receptor
    Irinotecan liposome injection
    Multi-drug delivery
    Photoimmunoconjugate
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077377648&doi=10.1186%2fs12951-019-0560-5&partnerID=40&md5=6bdcb944fca58df1c11a067fcb070662; http://hdl.handle.net/10713/11627
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12951-019-0560-5
    Scopus Count
    Collections
    UMB Open Access Articles 2020

    entitlement

    Related articles

    • Photochemical targeting of epidermal growth factor receptor: a mechanistic study.
    • Authors: Savellano MD, Hasan T
    • Issue date: 2005 Feb 15
    • Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience.
    • Authors: Glassman DC, Palmaira RL, Covington CM, Desai AM, Ku GY, Li J, Harding JJ, Varghese AM, O'Reilly EM, Yu KH
    • Issue date: 2018 Jun 27
    • Targeting cells that overexpress the epidermal growth factor receptor with polyethylene glycolated BPD verteporfin photosensitizer immunoconjugates.
    • Authors: Savellano MD, Hasan T
    • Issue date: 2003 Apr
    • Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing's family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression.
    • Authors: Kang MH, Wang J, Makena MR, Lee JS, Paz N, Hall CP, Song MM, Calderon RI, Cruz RE, Hindle A, Ko W, Fitzgerald JB, Drummond DC, Triche TJ, Reynolds CP
    • Issue date: 2015 Mar 1
    • Extended topoisomerase 1 inhibition through liposomal irinotecan results in improved efficacy over topotecan and irinotecan in models of small-cell lung cancer.
    • Authors: Leonard SC, Lee H, Gaddy DF, Klinz SG, Paz N, Kalra AV, Drummond DC, Chan DC, Bunn PA, Fitzgerald JB, Hendriks BS
    • Issue date: 2017 Nov
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.