Journal
ACS APPLIED BIO MATERIALS
Volume 4, Issue 9, Pages 6799-6806Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.1c00527
Keywords
mitochondria; tigecycline; mitochondrial ribosome; cancer; nanoparticle
Funding
- IIT Gandhinagar
- DST [SB/NM/NB-1083/2017 (G), 6349]
- CSIR-UGC
- MHRD
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Researchers have developed mitochondria-targeted antibiotic-loaded nanoparticles that can enhance the effectiveness of antibiotics in cancer therapy and reduce toxicity to noncancerous cells. These nanoparticles improve cancer cell killing ability and show less toxicity towards noncancerous cells, potentially opening up a new avenue for anticancer therapy.
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 mitochondria] transcription and translational machinery. To address this, herein, we have engineered three different mitochondria-targeted cationic antibiotic (tigecydine)-loaded nanopartides 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 tigecydine-loaded nanopartide (Mito-TPP-Tig-NP) was shown to be homed into the mitochondria of AS49 lung cancer cells compared to the other cationic nanopartides. These Mito-TPP-Tig-NPs indeed triggered mitochondrial morphology damage and generation of reactive oxygen species (ROS). All the mitochondria-targeted tigecydine-loaded nanopartides showed improved cancer cell killing ability in AS49 and HeLa cervical cancer cells compared to free tigecydine. Moreover, Mito-TPP-Tig-NPs showed much less toxicity toward noncancerous human embryonic kidney cells (HEK293) compared to free tigecycline. These antibiotic-loaded mitochondria-targeted nanoparticles can open up an avenue toward anticancer therapy.
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