Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free
Chemotherapy-inhibiting tumor cell evolution<b> </b>to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible inc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Biophysica |
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| Online Access: | https://www.mdpi.com/2673-4125/2/4/33 |
| _version_ | 1797461219107405824 |
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| author | Philip Serwer Elena T. Wright |
| author_facet | Philip Serwer Elena T. Wright |
| author_sort | Philip Serwer |
| collection | DOAJ |
| description | Chemotherapy-inhibiting tumor cell evolution<b> </b>to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence. |
| first_indexed | 2024-03-09T17:16:17Z |
| format | Article |
| id | doaj.art-7b31c5e45dce4bcbb9b55ee39647fee1 |
| institution | Directory Open Access Journal |
| issn | 2673-4125 |
| language | English |
| last_indexed | 2024-03-09T17:16:17Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biophysica |
| spelling | doaj.art-7b31c5e45dce4bcbb9b55ee39647fee12023-11-24T13:35:31ZengMDPI AGBiophysica2673-41252022-10-012436638010.3390/biophysica2040033Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-FreePhilip Serwer0Elena T. Wright1Department of Biochemistry and Structural Biology, The University of Texas Health Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USADepartment of Biochemistry and Structural Biology, The University of Texas Health Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USAChemotherapy-inhibiting tumor cell evolution<b> </b>to drug-resistance is potentially suppressed by using a drug delivery vehicle (DDV) that has gating. Gating would be used to increase tumor-selectivity of delivery of DDV packaged drug. Tumor-selectivity increase would make possible increase in tumor-delivered drug dose, which would suppress opportunities to evolve drug resistance. Currently used DDVs do not have gating but gating is a natural feature of some bacteriophages (phages). Phage T4, which has recently been found highly persistent in murine blood, is a potential gated DDV. Thus, here, we proceed towards a T4-DDV by developing (1) improved procedure for generating high concentrations and amounts of phage T4, (2) elevated temperature-driven gate-opening and ethidium- and bleomycin-loading, and (3) purification of loaded T4 by rate zonal centrifugation. We test for loading by native agarose gel electrophoresis (AGE) with fluorescence detection. We observe loading in both phage T4 and T4 (tail-free) heads. The loaded particles have an openable, closed gate. Stored, mature T4 phages and phage heads do not release ethidium during at least a month at 4 °C and 6 days at 37 and 42 °C. Tumor-specific T4 phage delivery is projected via both the EPR effect and high T4 persistence.https://www.mdpi.com/2673-4125/2/4/33drug delivery vehiclegated nanoparticlemetastatic cancernative agarose gel electrophoresisultracentrifugation |
| spellingShingle | Philip Serwer Elena T. Wright Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free Biophysica drug delivery vehicle gated nanoparticle metastatic cancer native agarose gel electrophoresis ultracentrifugation |
| title | Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free |
| title_full | Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free |
| title_fullStr | Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free |
| title_full_unstemmed | Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free |
| title_short | Gated Ethidium- and Bleomycin-Loading in Phage T4 That Is Subsequently Purified Leak-Free |
| title_sort | gated ethidium and bleomycin loading in phage t4 that is subsequently purified leak free |
| topic | drug delivery vehicle gated nanoparticle metastatic cancer native agarose gel electrophoresis ultracentrifugation |
| url | https://www.mdpi.com/2673-4125/2/4/33 |
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