Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment

Narsireddy Amreddy; Anish Babu; Janani Panneerselvam; Akhil Srivastava; Ranganayaki Muralidharan; Allshine Chen; Yan D Zhao; Anupama Munshi; Rajagopal Ramesh

doi:10.1016/j.nano.2017.11.010

Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment

Nanomedicine. 2018 Feb;14(2):373-384. doi: 10.1016/j.nano.2017.11.010. Epub 2017 Nov 16.

Authors

Narsireddy Amreddy¹, Anish Babu¹, Janani Panneerselvam¹, Akhil Srivastava¹, Ranganayaki Muralidharan¹, Allshine Chen², Yan D Zhao³, Anupama Munshi⁴, Rajagopal Ramesh⁵

Affiliations

¹ Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
² Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁵ Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: rajagopal-ramesh@ouhsc.edu.

Abstract

Co-administration of functionally distinct anti-cancer agents has emerged as an efficient strategy in lung cancer treatment. However, a specially designed drug delivery system is required to co-encapsulate functionally different agents, such as a combination of siRNA and chemotherapy, for targeted delivery. We developed a folic acid (FA)-conjugated polyamidoamine dendrimer (Den)-based nanoparticle (NP) system for co-delivery of siRNA against HuR mRNA (HuR siRNA) and cis-diamine platinum (CDDP) to folate receptor-α (FRA) -overexpressing H1299 lung cancer cells. The co-delivery of HuR siRNA and CDDP using the FRA-targeted NP had a significantly greater therapeutic effect than did individual therapeutics. Further, the FRA-targeted NP exhibited improved cytotoxicity compared to non-targeted NP against lung cancer cells. Finally, the NP showed negligible toxicity towards normal MRC9 lung fibroblast cells. Thus, the present study demonstrates FRA-targeted Den nanoparticle system as a suitable carrier for targeted co-delivery of siRNA and chemotherapy agents in lung cancer cells.

Keywords: CDDP; Dendrimer; FRA; HuR siRNA; Lung cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Apoptosis / drug effects
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / therapy*
Cell Proliferation / drug effects
Cisplatin / pharmacology*
Combined Modality Therapy
Dendrimers / chemistry*
Drug Delivery Systems*
ELAV-Like Protein 1 / antagonists & inhibitors*
ELAV-Like Protein 1 / genetics
Folate Receptor 1 / metabolism*
Humans
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Lung Neoplasms / therapy
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
RNA, Small Interfering / genetics
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Dendrimers
ELAV-Like Protein 1
ELAVL1 protein, human
FOLR1 protein, human
Folate Receptor 1
PAMAM Starburst
RNA, Small Interfering
Cisplatin

Abstract

Publication types

MeSH terms

Substances

Grants and funding