Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.

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.

• Authors: Ashwinkumar A Bhirde, Bhaskara V Chikkaveeraiah, Avinash Srivatsan, Gang Niu, Albert J Jin, Ankur Kapoor, Zhe Wang, Sachin Patel, Vyomesh Patel, Alexander M Gorbach, Richard D Leapman, J Silvio Gutkind, Angela R Hight Walker, Xiaoyuan Chen
• Journal: ACS nano (ACS Nano) Vol. 8 Issue 5 Pg. 4177-89 (May 27 2014) ISSN: 1936-086X [Electronic] United States
• PMID: 24708375 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Drug Carriers
• Nanotubes, Carbon
• Phospholipids
• Polymers
• Polyethylene Glycols
• Doxorubicin

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Doxorubicin (administration & dosage)
• Drug Carriers
• Drug Delivery Systems
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Elasticity
• Female
• Humans
• Mice
• Mice, SCID
• Nanotechnology (methods)
• Nanotubes (chemistry)
• Nanotubes, Carbon (chemistry)
• Neoplasms (drug therapy, pathology)
• Phospholipids (chemistry)
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Quartz Crystal Microbalance Techniques
• Semiconductors
• Temperature
• Viscosity