Dual effect of F-actin targeted carrier combined with antimitotic drug on aggressive colorectal cancer cytoskeleton: Allying dissimilar cell cytoskeleton disrupting mechanisms.
A recent approach to colon cancer therapy is to employ selective drugs with specific extra/intracellular sites of action. Alteration of cytoskeletal protein reorganization and, subsequently, to cellular biomechanical behaviour during cancer progression highly affects the cancer cell progress. Hence, cytoskeleton targeted drugs are an important class of cancer therapy agents. We have studied viscoelastic alteration of the human colon adenocarcinoma cell line, SW48, after treatment with a drug delivery system comprising chitosan as the carrier and albendazole as the microtubule-targeting agent (MTA). For the first time, we have evaluated the biomechanical characteristics of the cell line, using the micropipette aspiration (MA) method after treatment with drug delivery systems. Surprisingly, employing a chitosan-albendazole pair, in comparison with both neat materials, resulted in more significant change in the viscoelastic parameters of cells, including the elastic constants (K1and K2) and the coefficient of viscosity (μ). This difference was more pronounced for cancer cells after 48h of the treatment. Microtubule and actin microfilament (F-actin) contents in the cell line were studied by immunofluorescent staining. Good agreement was observed between the mechanical characteristics results and microtubule/F-actin contents of the treated SW48 cell line, which declined after treatment. The results showed that chitosan affected F-actin more, while MTA was more effective for microtubules. Toxicity studies were performed against two cancer cell lines (SW48 and MCF10CA1h) and compared to normal cells, MCF10A. The results showed cancer selectiveness, safety of formulation, and enhanced anticancer efficacy of the CS/ABZ conjugate. This study suggests that employing such a suitable pair of drug-carriers with dissimilar sites of action, thus allying the different cell cytoskeleton disrupting mechanisms, may provide a more efficient cancer therapy approach.
Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, 3800, Australia; Laboratory for Biomedical Engineering/Fluids Laboratory for Aeronautical and Industrial Research, Department of Mechanical and Aerospace Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, 3800, Australia.
Shahrouz
S
Taranejoo
BioMEMS and Bioinspired Microfluidic Laboratory, Center for BioEngineering Research and Education, Department of Mechanical and Manufacturing Engineering, University of Calgary, Canada; Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran, Iran.
Mohsen
M
Janmaleki
BioMEMS and Bioinspired Microfluidic Laboratory, Center for BioEngineering Research and Education, Department of Mechanical and Manufacturing Engineering, University of Calgary, Canada; Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Taleghani Hospital, Tehran, Iran.
Mohammad
M
Pachenari
Institute of Mechanics, Structural Analysis, and Dynamics, Faculty of Architecture and Civil Engineering, TU Dortmund, August-Schmidt-Strasse 6, 44227 Dortmund, Germany.
Seyed Morteza
SM
Seyedpour
Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, 3800, Australia.
Ramya
R
Chandrasekaran
Department of Chemical Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, 3800, Australia.
Wenlong
W
Cheng
Laboratory for Biomedical Engineering/Fluids Laboratory for Aeronautical and Industrial Research, Department of Mechanical and Aerospace Engineering, Faculty of Engineering, Monash University, Melbourne, VIC, 3800, Australia. Electronic address: kerry.hourigan@monash.edu.
Kerry
K
Hourigan
D000199:Actins / Q000378:metabolism*; D015766:Albendazole / Q000008:administration & dosage* / Q000737:chemistry; D050256:Antimitotic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D004548:Elasticity; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
D000199:Actins; D050256:Antimitotic Agents; D004337:Drug Carriers; D048271:Chitosan; D015766:Albendazole
Actin microfilaments; Albendazole; Cancer; Cytoskeleton; Microtubule-targeting agent; Microtubules