Journal article
Engineered triphenylphosphonium-based, mitochondrial-targeted liposomal drug delivery system facilitates cancer cell killing actions of chemotherapeutics
RSC chemical biology, Vol.5(3), pp.236-248
03/06/2024
DOI: 10.1039/d3cb00219e
PMCID: PMC10915973
PMID: 38456034
Abstract
In addition to their classical role in ATP generation, mitochondria also contribute to Ca2+ buffering, free radical production, and initiation of programmed cell death. Mitochondrial dysfunction has been linked to several leading causes of morbidity and mortality worldwide including neurodegenerative, metabolic, and cardiovascular diseases as well as several cancer subtypes. Thus, there is growing interest in developing drug-delivery vehicles capable of shuttling therapeutics directly to the mitochondria. Here, we functionalized the conventional 10,12-pentacosadiynoic acid/1,2-dimyristoyl-sn-glycero-3-phosphocholine (PCDA/DMPC)-based liposome with a mitochondria-targeting triphenylphosphonium (TPP) cationic group. A fluorescent dansyl dye (DAN) group was also included for tracking mitochondrial drug uptake. The resultant PCDA-TPP and PCDA-DAN conjugates were incorporated into a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based lipid bilayer, and these modified liposomes (Lip-DT) were studied for their cellular toxicity, mitochondrial targeting ability, and efficacy in delivering the drug Doxorubicin (Dox) to human colorectal carcinoma (HCT116) and human breast (MCF7) cancer cells in vitro. This Lip-DT-Dox exhibited the ability to shuttle the encapsulated drug to the mitochondria of cancer cells and triggered oxidative stress, mitochondrial dysfunction, and apoptosis. The ability of Lip-DT-Dox to trigger cellular toxicity in both HCT116 and MCF7 cancer cells was comparable to the known cell-killing actions of the unencapsulated drug (Dox). The findings in this study reveal a promising approach where conventional liposome-based drug delivery systems can be rendered mitochondria-specific by incorporating well-known mitochondriotropic moieties onto the surface of the liposome.
Lip-DT represents an important proof-of-concept exercise demonstrating that functionalized PCDA/DMPC-based liposomes have great promise for the development of new imaging probes and targeted drug-delivery vehicles.
Details
- Title: Subtitle
- Engineered triphenylphosphonium-based, mitochondrial-targeted liposomal drug delivery system facilitates cancer cell killing actions of chemotherapeutics
- Creators
- Subramaniyam Sivagnanam - SRM Institute of Science and TechnologyKiran Das - Centre of Biomedical ResearchIeshita Pan - Saveetha UniversityAdele Stewart - Florida Atlantic UniversityAtanu Barik - Bhabha Atomic Research CentrePriyadip Das - SRM Institute of Science and TechnologyBiswanath Maity - Centre of Biomedical Research
- Resource Type
- Journal article
- Publication Details
- RSC chemical biology, Vol.5(3), pp.236-248
- Publisher
- Royal Soc Chemistry
- DOI
- 10.1039/d3cb00219e
- PMID
- 38456034
- PMCID
- PMC10915973
- ISSN
- 2633-0679
- eISSN
- 2633-0679
- Number of pages
- 13
- Grant note
- 58/14/14/2021-BRNS/37219 / Board of Research in Nuclear Sciences; Department of Atomic Energy (DAE); Board of Research in Nuclear Sciences (BRNS) Board of Research in Nuclear Sciences (BRNS), India; Department of Atomic Energy (DAE); Board of Research in Nuclear Sciences (BRNS) Indian Council of Medical Research; Indian Council of Medical Research (ICMR) ICMR - 5/4/1-26/2020-NCD-I; 5/4/1-22/CVD/2022-NCD-I / Department of Biotechnology (DBT); Department of Biotechnology (DBT) India
- Language
- English
- Date published
- 03/06/2024
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984618640002771
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