Targeted Therapeutic Nanotubes Influence the Viscoelasticity of Cancer Cells to Overcome Drug Resistance

Autor: 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, Ashwinkumar Bhirde
Rok vydání: 2014
Předmět:
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
Zdroj: ACS Nano
ISSN: 1936-086X
1936-0851
Popis: 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.
Databáze: OpenAIRE
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