Abstract
In current cancer therapy, the combined targeted delivery of treatments is an important method to enhance the therapeutic efficiency and reduce adverse side effects. Dendrimer-based nanoparticles have received considerable attention for multifunctional therapeutic delivery. In this chapter, we describe the methods for encapsulating the chemotherapeutic drug, cisplatin (CDDP), and human antigen R (HuR)-targeted siRNA into dendrimer nanoparticles for folate receptor-targeted delivery. We discuss the methodologies for physical and biological characterization of synthesized multifunctional (Den-PEI-CDDP-HuR-FA) nanoparticles in detail. Physical characterization includes size and charge determination, drug encapsulation and release kinetics, ligand conjugation, etc., and functional characterization involves testing of the nanoparticles for receptor-specific uptake and cytotoxicity on human lung cancer and normal cells. The protocol provided is geared to provide the readers an overview of developing multifunctional dendrimer-based nanoparticles. However, based on the individual’s objective and the type of combinatorial drugs to deliver, the protocol may need modifications in achieving maximal efficacy.
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Acknowledgments
The work was supported in part by grants (R01 CA167516 and R01CA233201) received from the National Institutes of Health (NIH), an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences (P20 GM103639) of the National Institutes of Health, a Merit Review grant from the Department of Veterans Affairs (VA)(101BX003420A1), the Oklahoma Center for the Advancement of Science and Technology (OCAST; HR18-088), a pilot grant from the Stephenson Cancer Center funded by the NCI Cancer Center Support Grant (P30CA225520) awarded to the University of Oklahoma Stephenson Cancer Center and by funds received from the Stephenson Cancer Center Seed Grant (R.R.), Presbyterian Health Foundation Seed Grant (R.R., A.M.), Presbyterian Health Foundation Bridge Grant (R.R., A.M.), and Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics (R.R.) at the University of Oklahoma Health Sciences Center. Rebaz Ahmed is a recipient of the Stephenson Cancer Center Trainee Research Award funded by the National Cancer Institute Cancer Center Support Grant P30CA225520 awarded to the University of Oklahoma Stephenson Cancer Center. Rajagopal Ramesh is an Oklahoma TSET Research Scholar and holds the Jim and Christy Everest Endowed Chair in Cancer Developmental Therapeutics. The authors thank Ms. Kathy Kyler at the office of Vice President for Research, OUHSC, for editorial assistance.
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Amreddy, N., Ahmed, R.A., Munshi, A., Ramesh, R. (2020). Tumor-Targeted Dendrimer Nanoparticles for Combinatorial Delivery of siRNA and Chemotherapy for Cancer Treatment. In: Jain, K. (eds) Drug Delivery Systems. Methods in Molecular Biology, vol 2059. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9798-5_8
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DOI: https://doi.org/10.1007/978-1-4939-9798-5_8
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