Engineered triphenylphosphonium-based, mitochondrial-targeted liposomal drug delivery system facilitates cancer cell killing actions of chemotherapeutics.

Sivagnanam, Subramaniyam; Das, Kiran; Pan, Ieshita; Stewart, Adele; Barik, Atanu; Maity, Biswanath; Das, Priyadip

Sivagnanam, Subramaniyam; Das, Kiran; Pan, Ieshita; Stewart, Adele; Barik, Atanu; Maity, Biswanath; Das, Priyadip.

Afiliación

Sivagnanam S; Department of Chemistry, SRM Institute of Science and Technology SRM Nagar, Potheri Kattankulathur Tamil Nadu-603203 India priyadipcsmcri@gmail.com priyadip@srmist.edu.in.
Das K; Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI) campus Raebareli Road Lucknow Uttar Pradesh 226014 India bmaity28@gmail.com bmaity@cbmr.res.in.
Pan I; Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University Chennai 602105 Tamil Nadu India.
Stewart A; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University Jupiter FL 33458 USA.
Barik A; Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay Mumbai 400085 Maharashtra India.
Maity B; Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI) campus Raebareli Road Lucknow Uttar Pradesh 226014 India bmaity28@gmail.com bmaity@cbmr.res.in.
Das P; Department of Chemistry, SRM Institute of Science and Technology SRM Nagar, Potheri Kattankulathur Tamil Nadu-603203 India priyadipcsmcri@gmail.com priyadip@srmist.edu.in.

RSC Chem Biol ; 5(3): 236-248, 2024 Mar 06.

Article en En | MEDLINE | ID: mdl-38456034

ABSTRACT

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.

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: RSC Chem Biol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido

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