Nanoparticle-Mediated Routing of Antibiotics into Mitochondria in Cancer Cells

Abstract

In recent years, antibiotics have emerged as alternative medicines in cancer therapy due to their capability of mitochondrial dysfunction in cancer cells. However, antibiotics render collateral damage in noncancerous cells by targeting mitochondrial transcription and translational machinery. To address this, herein, we have engineered three different mitochondria-targeted cationic antibiotic (tigecycline)-loaded nanoparticles from cholesterol conjugates. Dynamic light scattering and electron microscopy confirmed the spherical morphology and a less than 200 nm hydrodynamic diameter for these nanoparticles. The triphenylphosphine-coated tigecycline-loaded nanoparticle (Mito-TPP-Tig-NP) was shown to be homed into the mitochondria of A549 lung cancer cells compared to the other cationic nanoparticles. These Mito-TPP-Tig-NPs indeed triggered mitochondrial morphology damage and generation of reactive oxygen species (ROS). All the mitochondria-targeted tigecycline-loaded nanoparticles showed improved cancer cell killing ability in A549 and HeLa cervical cancer cells compared to free tigecycline. Moreover, Mito-TPP-Tig-NPs showed much less toxicity toward noncancerous human embryonic kidney cells (HEK293) compared to free tigecycline. These antibiotic-loaded mitochondriatargeted nanoparticles can open up an avenue toward anticancer therapy.

Chimeric nanoparticles for targeting mitochondria in cancer cells

“… 27 We have incorporated a cholesterol–triphenylphosphine conjugate (5) to target mitochondria, as the positively charged triphenylphosphine (TPP) moiety localizes the nanoparticles at sub-cellular mitochondria. 28 The loading of cisplatin, camptothecin, and tigecycline was quantified based on UV-vis spectroscopy (Fig. S4a, ESI † ).…”

Azadirachta indica Seed Derived Carbon Nanocapsules: Cell Imaging, Depolarization of Mitochondrial Membrane Potential, and Dose-Dependent Control Death of Breast Cancer

“…It is a quite recognized fact that the mitochondria plays an important role in the apoptotic cascade by serving as convergent signals of apoptotic cells for both the pathway, i.e., intrinsic and extrinsic pathways . The mitochondrial potential charges show determinant to carrying out the cell death. − Henceforth, to know the process of apoptosis in different cancer cell lines, and the change in the mitochondrial membrane potential on the different treatments of synthesized carbon nanocapsules were examined. Rhodamine 123 (Rh 123) has been used to estimate the mitochondrial membrane potential.…”

Subcellular delivery of lipid nanoparticles to endoplasmic reticulum and mitochondria

“…Once entering the lysosome of tumor cells, the positively charged TPP was exposed and the nanoparticles escaped from the lysosome to be bound with the negative membrane of mitochondria and nucleus, thereby improving the therapeutic effect of DOX while decreasing its systemic toxicity. Bajpai et al (2021) grafted cholesterol respectively with TPP, Pyridine (Py), and N,N-dimethylaminopyridine (DMAP), and prepared three Tigecycline-loaded lipid nanoparticles (Mito-TPP-Tig-NPs, Mito-Py-Tig-NPs and Mito-DMAP-Tig-NPs) based on the resultant cholesterol conjugates (cholesterol conjugates:PC: DSPE-PEG 2000 = 1:2:0.2, w/w). These nanoparticles all displayed positive surface charges (+31.9 mV with TPP, +29.8 mV with Py, and +22.6 mV with DMAP) that favored a mitochondria-targeted subcellular trafficking.…”

“…Bajpai et al (2021) grafted cholesterol respectively with TPP, Pyridine (Py), and N , N ‐dimethyl‐aminopyridine (DMAP), and prepared three Tigecycline‐loaded lipid nanoparticles (Mito‐TPP‐Tig‐NPs, Mito‐Py‐Tig‐NPs and Mito‐DMAP‐Tig‐NPs) based on the resultant cholesterol conjugates (cholesterol conjugates:PC:DSPE‐PEG 2000 = 1:2:0.2, w/w). These nanoparticles all displayed positive surface charges (+31.9 mV with TPP, +29.8 mV with Py, and +22.6 mV with DMAP) that favored a mitochondria‐targeted subcellular trafficking.…”