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Research Article

Antihepatoma Activity of Multifunctional Polymeric Nanoparticles Via Inhibition of Microtubules and Tyrosine Kinases

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Pages 381-396 | Received 21 Sep 2019, Accepted 10 Dec 2019, Published online: 28 Jan 2020
 

Abstract

Aim: Synthesis of poly-L-lactic acid nanoparticles comprising of microtubule-inhibitor docetaxel and tyrosine kinase inhibitor sorafenib (PLDS NPs) for hepatoma treatment. Materials & methods: PLDS NPs were prepared by the emulsion solvent evaporation method and the anticancer activity was evaluated in Huh7 hepatoma cells. Results: Real-time imaging of quantum dots incorporating poly-L-lactic acid nanoparticles showed a rapid internalization of the nanoparticles in Huh7 cells. PLDS NPs exerted stronger antiproliferative, apoptotic and antiangiogenic effects than free single drug counterparts. They strongly promoted microtubule bundling, multinucleation and increased mitotic index in Huh7 cells. They also inhibited the expression of pERK1/2, pAKT and cyclin D1. Conclusion: We developed a single-nanoscale platform for dual drug delivery and high-sensitivity quantum dots imaging for hepatoma treatment.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2019-0349

Author contributions

R Poojari conceptualized the work, performed experiments and wrote the manuscript, AV Sawant performed experiments and participated in manuscript preparation, S Kini performed experiments and participated in the manuscript preparation, R Srivastava provided the resources for the nanoparticle synthesis. D Panda provided the resources, supervised the work and participated in the manuscript preparation. All the authors critically analyzed the data, revised the manuscript, read and approved the final manuscript.

Financial & competing interests disclosure

The present research work was supported by a BioCare research grant (BT/PR18833/BIC/101/409/2016) from the Department of Biotechnology (DBT), Government of India, to R Poojari and Tata Innovation Fellowship to D Panda. This work is a part of Indian Patent no. 315542 granted to R Poojari, D Panda and R Srivastava, Indian Institute of Technology Bombay, Mumbai, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

AV Sawant is thankful to UGC for his fellowship. The authors are grateful to Dr S Purandare from Cipla Ltd, India for the generous gift of Sorafenib. To Purac Biomaterials, The Netherlands, for the kind provision of PLA polymer. To Dr M Sadawana, IIT Bombay, India, for the in-house synthesized quantum dots. The authors acknowledge Prof S Das, IISc, Bangalore, India, for kindly providing the Huh7 cells. To Centre for Research in Nanotechnology and Science for the characterization and flow cytometry facilities and Central Surface Analytical Facility for the AFM, XPS at IIT Bombay, India. The authors thank Dr D Bhattacharyya from Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), India, for providing the real-time CLSM and optical inverted microscopy digital imaging facility. The authors thank Professor PW Groundwater, University of Sydney, Australia, for the critical reading of our manuscript.

Additional information

Funding

The present research work was supported by a BioCare research grant (BT/PR18833/BIC/101/409/2016) from the Department of Biotechnology (DBT), Government of India, to R Poojari and Tata Innovation Fellowship to D Panda. This work is a part of Indian Patent no. 315542 granted to R Poojari, D Panda and R Srivastava, Indian Institute of Technology Bombay, Mumbai, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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