Triphenyl Phosphine-Functionalized Chitosan Nanoparticles Enhanced Antitumor Efficiency Through Targeted Delivery of Doxorubicin to Mitochondria

Abstract

Mitochondria as an important organ in eukaryotic cells produced energy through oxidative phosphorylation and also played an important role in regulating the apoptotic signal transduction process. Importantly, mitochondria like nuclei also contained the functional DNA and were very sensitive to anticancer drugs which could effectively inhibit the synthesis of nucleic acid, especially the production of DNA. In this work, we designed novel triphenyl phosphine (TPP)-conjugated chitosan (CS) nanoparticles (NPs) for efficient drug delivery to cell mitochondria. The results showed that compared with free doxorubicin (Dox), Dox-loaded TPP-NPs were specifically distributed in mitochondria of tumor cells and interfered with the function of mitochondria, thus resulted in the higher cytotoxicity and induced the significant cell apoptosis effect. Taken together, triphenyl phosphine-conjugated chitosan nanoparticles may become a promising mitochondria-targeting nanocarrier candidate for enhancing antitumor effects.

Alteration of the Mitochondrial Effects of Ceria Nanoparticles by Gold: An Approach for the Mitochondrial Modulation of Cells Based on Nanomedicine

“…Different types of NPs have been proposed for various biomedical applications such as drug delivery, bioimaging, thermotherapy and antioxidant therapy [1][2][3][4][5]. Furthermore, NPs can be functionalized to recognize specific biological targets, improving their effect; for example, triphenylphosphonium (TPP) and anti-HER2 can be used to target mitochondria [6,7] or specific tumor cells [8], respectively. Among all types of NPs proposed for biomedical applications, ceria NPs (CeO 2 ) are among the most promising due to their physicochemical properties, versatility and biocompatibility [9].…”

Chamaejasmin B Decreases Malignant Characteristics of Mouse Melanoma B16F0 and B16F10 Cells

“…Apoptosis is another essential bio-process for maintaining cell and tissue homeostasis. Mitochondria not only produce most of the ATP but also regulate metabolism and programmed cell death, thus playing a vital role in cell survival and death (30). In addition, they are known as the main source of ROS in many cell types.…”

Selenium as a pleiotropic agent for medical discovery and drug delivery

“…102 Many diseases are associated with mitochondrial dysfunction, including cancer, cardiovascular diseases, diabetes, and neurological disorders. Certain organic cations can penetrate the mitochondrial membrane and can be employed to deliver therapeuticals into the mitochondria, such as chitosan 103 and triphenylphosphonium. 104 These cationic compounds can be utilized to fabricate SeNPs through covalent conjugation for targeted drug delivery.…”