Codelivery of DOX and siRNA by folate-biotin-quaternized starch nanoparticles for promoting synergistic suppression of human lung cancer cells

Liangping Li; Suoju He; Lizhen Yu; Ezzat H Elshazly; Hui Wang; Kuanmin Chen; Song Zhang; Lixia Ke; Renmin Gong

doi:10.1080/10717544.2019.1606363

Codelivery of DOX and siRNA by folate-biotin-quaternized starch nanoparticles for promoting synergistic suppression of human lung cancer cells

Drug Deliv. 2019 Dec;26(1):499-508. doi: 10.1080/10717544.2019.1606363.

Authors

Liangping Li^{1

2}, Suoju He¹, Lizhen Yu^{1

3}, Ezzat H Elshazly^{1

4}, Hui Wang¹, Kuanmin Chen¹, Song Zhang¹, Lixia Ke¹, Renmin Gong¹

Affiliations

¹ a College of Life Science, Anhui Normal University , Wuhu , P R China.
² b Department of Physical Education , Anhui College of Traditional Chinese Medicine , Wuhu , P R China.
³ c School of Pharmacy , Wannan Medical College , Wuhu , P R China.
⁴ d Department of Botany and Microbiology, Faculty of Science , Al Azhar University , Assiut , Egypt.

Abstract

In this paper, the self-assembled folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as carrier system of doxorubicin (DOX) and siRNA^IGF1R for the codelivery of both into human lung adenocarcinoma cell lines (A549 cells) in vitro. The cytotoxicity, targeted ligand competition, cell proliferation inhibition, cellular uptake, endocytosis mechanism and target protein suppression of drug-loaded FBqS NPs were evaluated in detail. Compared with several other drug formulations under same condition, siRNA^IGF1R/DOX/FBqS NPs exhibited the greatest cytotoxicity to A549 cells and the cytotoxicity was competitively inhibited by free folate in dose-dependent manner. The A549 cells treated by siRNA^IGF1R/DOX/FBqS NPs showed the lowest cell proliferation capacity. The energy-dependent clathrin- and caveolae-mediated endocytosis might be the primary cellular uptake mechanism of drug-loaded FBqS NPs. The expression of IGF1R protein in A549 cells treated by siRNA^IGF1R/FBqS NPs declined dramatically. So the FBqS NPs were expected as the co-carrier system of chemotherapeutants and siRNAs for future clinical application.

Keywords: Folate-biotin-quaternized starch nanoparticle; codelivery; doxorubicin; human lung cancer cell lines; siRNA.

MeSH terms

A549 Cells
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / pharmacology
Biotin / chemistry
Cell Survival / drug effects
Doxorubicin / administration & dosage*
Doxorubicin / pharmacology
Drug Carriers / chemistry*
Drug Synergism
Endocytosis / drug effects
Folic Acid / chemistry
Humans
Lung Neoplasms / pathology
Nanoparticles / chemistry*
Particle Size
RNA, Small Interfering / administration & dosage*
RNA, Small Interfering / pharmacology
Starch / chemistry

Substances

Antineoplastic Agents
Drug Carriers
RNA, Small Interfering
Biotin
Doxorubicin
Starch
Folic Acid

Grants and funding

This work was financially supported by the Excellent Young Support Program of Higher Education Institutions of Anhui Province (No. gxyqZD2017116); the Key Laboratory of Biotic Environment and Ecological Safety of Anhui Province; the Key Laboratory of Bioresource Protection and Utilization of Anhui Province; the Innovation Team of Scientific Research Platform in Anhui Universities; and the Key Laboratory of Biomedicine in Gene Diseases and Health of Anhui Higher Education Institutes, Anhui Normal University.