Synthesis of Triphenylphosphonium Phospholipid Conjugates for the Preparation of Mitochondriotropic Liposomes
Abstract
Surface modification of liposomes with a ligand is facilitated by the conjugation of the ligand to a hydrophobic molecule that serves to anchor the ligand to the liposomal bilayer. We describe here a simple protocol to conjugate a triphenylphosphonium group to several commercially available functionalized phospholipids. The resulting triphenylphosphonium-conjugated lipids can be used to prepare liposomes that preferentially associate with mitochondria when exposed to live mammalian cells in culture.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Monolayer systems fall short in predicting in vivo therapeutic efficacy despite their utility in mechanistic studies and target validation.
“However, despite their utility in mechanistic studies and target validation, these models fall short in predicting in vivo therapeutic efficacy.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [171]
Numerous anticancer compounds that demonstrate robust activity in monolayer cultures fail to reproduce such outcomes in vivo.
“Numerous anticancer compounds that demonstrate robust activity in monolayer cultures fail to reproduce such outcomes in vivo [168,169,170,171].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [171]
Cites
Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., Cheng, G., Lopez, M., & Kalyanaraman, B. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00042 · Cited by 1,683 · see citing works
Targeting mitochondria for cancer therapy
Fulda, S., Galluzzi, L., & Kroemer, G. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3137 · Cited by 1,638 · see citing works
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations
Murphy, M. P., & Smith, R. A. J. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105110 · Cited by 1,173 · see citing works
Breaking the mitochondrial barrier
Martinou, J., & Green, D. R. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35048069 · Cited by 951 · see citing works
Targeting lipophilic cations to mitochondria
Murphy, M. P. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.03.029 · Cited by 598 · see citing works
Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics
Marrache, S., & Dhar, S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210096109 · Cited by 497 · see citing works
Drug delivery to mitochondria: the key to mitochondrial medicine
Murphy, M. P., & Smith, R. A. J. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(99)00069-1 · Cited by 426 · see citing works
Mitochondria-Targeted Small Molecule Therapeutics and Probes
Smith, R. A. J., Hartley, R. C., & Murphy, M. P. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.3969 · Cited by 399 · see citing works
The development of mitochondrial medicine.
Luft, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8731 · Cited by 302 · see citing works
Yamada, Y., & Harashima, H. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.04.016 · Cited by 258 · see citing works
Boddapati, S. V., D’Souza, G. G. M., Erdoğan, S., Torchilin, V. P., & Weissig, V. (2008) · Nano Letters · doi:10.1021/nl801908y · Cited by 234 · see citing works
Self-citationBoddapati, S. V., Tongcharoensirikul, P., Hanson, R. N., D’Souza, G. G. M., Torchilin, V. P., & Weissig, V. (2005) · Journal of Liposome Research · doi:10.1081/lpr-64958 · Cited by 129 · see citing works
Self-citationApproaches for targeting mitochondria in cancer therapy
D’Souza, G. G. M., Wagle, M. A., Saxena, V., & Shah, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.08.008 · Cited by 118 · see citing works
Self-citationMitochondria-targeted liposomes improve the apoptotic and cytotoxic action of sclareol
Patel, N. R., Hatziantoniou, S., Georgopoulos, A., Demetzos, C., Torchilin, V. P., Weissig, V., & D’Souza, G. G. M. (2009) · Journal of Liposome Research · doi:10.3109/08982100903347931 · Cited by 81 · see citing works
Self-citationFrom Serendipity to Mitochondria-Targeted Nanocarriers
Weissig, V. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0556-9 · Cited by 79 · see citing works
Novel HPMA Copolymer-Bound Constructs for Combined Tumor and Mitochondrial Targeting
Cuchelkar, V., Kopečková, P., & Kopec̆ek, J. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800019g · Cited by 57 · see citing works
Synthesis of triphenylphosphonium vitamin E derivatives as mitochondria-targeted antioxidants
Jameson, V. J. A., Cochemé, H. M., Logan, A., Hanton, L. R., Smith, R. A. J., & Murphy, M. P. (2015) · Tetrahedron · doi:10.1016/j.tet.2015.09.014 · Cited by 46 · see citing works
Solomon, M. A., Shah, A. A., & D'Souza, G. G. M. (2013) · Mitochondrion · doi:10.1016/j.mito.2012.10.013 · Cited by 39 · see citing works
Self-citationBenien, P., Solomon, M. A., Nguyen, P., Sheehan, E., Mehanna, A. S., & D’Souza, G. G. M. (2015) · Journal of Liposome Research · doi:10.3109/08982104.2015.1022557 · Cited by 24 · see citing works
Self-citationMultiple Triphenylphosphonium Cations as a Platform for the Delivery of a Pro-Apoptotic Peptide
Kolevzon, N., Kuflik, U., Shmuel, M., Benhamron, S., Ringel, I., & Yavin, E. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0494-6 · Cited by 20 · see citing works
Mitochondrial Delivery of Biologically Active Molecules
Weissig, V. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0588-1 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
Self-citation
- Authors
- Benien, P., Almuteri, M., Shah, S., Böhlke, M., Mehanna, A., & D’Souza, G. G. M.
- Affiliations
- Massachusetts College of Pharmacy and Health Sciences (US)
- Corresponding author
- D’Souza, Gerard G. M.
- Venue
- Methods in molecular biology
- Publisher
- Springer US
- Published
- 2021
- Pages
- 119-126
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W3172475792
- Cited by
- 4
- References
- 21
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2
- FWCI
- 1.14
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Methods in molecular biology (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- triphenylphosphonium, liposome surface modification, mitochondrial targeting
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
