Triphenylphosphine-Based Mitochondrial Targeting Nanocarriers: Advancing Cancer Therapy

Mohd Shoab Ali,1 BH Jaswanth Gowda,2 Rahul Shukla,3 Prashant Kesharwani1 1Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India; 2Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, KA, 575018, India; 3Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER, Raebareli), Raebareli, 226301, IndiaCorrespondence: Prashant Kesharwani, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India, Tel/Fax +91 7999710141, Email [email protected]: Numerous chemotherapeutic drugs are commercially available for cancer treatment; however, their efficacy is often compromised by diminishing therapeutic effectiveness and unpredictable adverse effects. The lack of specific targeting limits their optimal therapeutic potential. Mitochondria are the primary sites of cellular energy production and play a critical role in cell survival and death. Furthermore, numerous studies have found an apparent association between mitochondrial metabolism and carcinogenesis and progression. Therefore, significant attention has been directed toward nanocarriers specifically designed for mitochondrial delivery, aiming to enhance the precision of chemotherapeutic agent transport to these critical organelles. Among these, triphenylphosphonium has emerged as a prominent mitochondrial targeting agent due to its superior targeting capabilities. This approach not only reduces the required drug dosage but also minimizes adverse effects on healthy tissues. This review provides a concise analysis of nanotechnology’s contributions to cancer therapy, emphasizing its potential for targeting at both cellular and sub-cellular levels. Additionally, it delves into mitochondrial targeting, with a particular focus on nanocarriers engineered for efficient mitochondrial drug delivery. Moreover, it focuses on strategies employed by researchers to introduce TPP in nanocarrier systems for mitochondrial delivery and concludes by addressing challenges associated with TPP including hemolytic activity and how researchers mitigate this issue. Keywords: nanomedicine, cancer, mitochondrial targeting, triphenylphosphine, nanoparticles