Mitochondria-Targeted Chimeric Peptide for Trinitarian Overcoming of Drug Resistance
Kai Han1, Jing-Yi Zhu2, Hui-Zhen Jia2
1State Key Laboratory of Agricultural Microbiology, College of Science, Huazhong Agricultural University , Wuhan 430070, China.
Abstract:
In this report, an amphiphilic mitochondria-targeted chimeric peptide-based drug delivery system (DDS) was designed to overcome drug resistance. In vitro studies revealed that chimeric peptide could encapsulate doxorubicin (DOX) with high efficacy and target tumor mitochondria, realizing controlled release of DOX and in situ photodynamic therapy (PDT) in mitochondria. Importantly, reactive oxygen species (ROS) during PDT significantly disrupted mitochondria, leading to a dramatic decrease of intracellular adenosine 5'-triphophate (ATP). As a result, ATP-dependent efflux of DOX was remarkably inhibited. Trinitarian therapeutic strategy was developed to ablation of drug-resistant cells, that is, (1) enhanced cellular uptake of hydrophobic DOX via encapsulation in DDS, (2) combined chemo-/photodynamic therapies, and (3) suppressed generation of intracellular ATP as well as drug efflux via in situ PDT in mitochondria. This trinitarian strategy may open a new window in the fabrication of subcellular organelle destructive DDS in overcoming drug resistance.
More Related Videos
14:20Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
Related Concept Videos
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Mitochondrial Precursor Proteins
Most of the mitochondrial...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
