1. Targeted Therapeutic Nanotubes Influence the Viscoelasticity of Cancer Cells to Overcome Drug Resistance
- Author
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Angela R. Hight Walker, Ankur Kapoor, Zhe Wang, Avinash Srivatsan, Richard D. Leapman, Xiaoyuan Chen, J. Silvio Gutkind, Sachin Patel, Gang Niu, Bhaskara V. Chikkaveeraiah, Alexander M. Gorbach, Albert J. Jin, Vyomesh Patel, and Ashwinkumar Bhirde
- Subjects
Polymers ,medicine.medical_treatment ,General Physics and Astronomy ,Apoptosis ,Mice, SCID ,Drug resistance ,Polyethylene Glycols ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,Neoplasms ,hyaluronic acid ,Hyaluronic acid ,polycyclic compounds ,Nanotechnology ,General Materials Science ,viscoelasticity ,Phospholipids ,Drug Carriers ,Nanotubes ,Viscosity ,Temperature ,General Engineering ,Drug Resistance, Multiple ,Drug delivery ,Female ,Drug carrier ,medicine.drug ,Materials science ,semiconducting carbon nanotube ,macromolecular substances ,doxorubicin ,Article ,multidrug resistance ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Doxorubicin ,Chemotherapy ,Nanotubes, Carbon ,technology, industry, and agriculture ,quartz-crystal microbalance with dissipation (QCM-D) ,Elasticity ,carbohydrates (lipids) ,Multiple drug resistance ,live cell imaging ,Semiconductors ,chemistry ,Drug Resistance, Neoplasm ,Cancer cell ,Quartz Crystal Microbalance Techniques ,Cancer research - Abstract
Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm(2), 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.
- Published
- 2014