Promoted delivery of salinomycin sodium to lung cancer cells by dual targeting PLGA hybrid nanoparticles

Zhou,Jie; Sun,Jin; Chen,Huaiwen; Peng,Qing

doi:10.3892/ijo.2018.4474

Promoted delivery of salinomycin sodium to lung cancer cells by dual targeting PLGA hybrid nanoparticles

Authors:
- Jie Zhou
- Jin Sun
- Huaiwen Chen
- Qing Peng
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Affiliations: Department of Pulmonary Medicine, Minhang Hospital, Zhongshan Hospital, Fudan University, Shanghai 201199, P.R. China, Department of Pharmacy, The Naval Medical University, Shanghai 200433, P.R. China, Center of Clinical and Translational Medicine, Shanghai Changhai Hospital, The Naval Medical University, Shanghai 200433, P.R. China
Published online on: July 6, 2018 https://doi.org/10.3892/ijo.2018.4474
Pages: 1289-1300

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Abstract

As the leading cause of cancer-associated mortality worldwide, lung cancer is often associated with therapy failure and decreases in survival; these factors are often attributed to lung cancer-initiating cells (CICs). In addition, sufficient evidence has suggested that simultaneous targeting of CICs, together with cancer cells, is critical for the achievement of preferable therapeutic efficacy, due to the spontaneous conversion between CICs and cancer cells. Salinomycin sodium (SS) is an antibacterial therapeutic agent that exerts potent activity against CICs in various types of cancer, including lung cancer. The present study generated SS lipid-polymer hybrid nanoparticles (NPs) with cluster of differentiation (CD)133 and epidermal growth factor receptor (EGFR) antibodies (CD133/EGFR SS NPs) for the simultaneous treatment of lung CICs and cancer cells. The activity of CD133/EGFR SS NPs was analyzed using cytotoxicity and tumorsphere formation assays, flow cytometry, and an in vivo anticancer assay in mice bearing lung cancer xenografts. The results revealed that CD133/EGFR SS NPs effectively promoted SS delivery to lung CICs and cancer cells, achieving superior therapeutic effects compared with non-targeted NPs or NPs with a single antibody. Furthermore, CD133/EGFR SS NPs exhibited the best efficacy in inhibiting tumor growth compared with the control agents in lung cancer-bearing mice. In conclusion, CD133/EGFR SS NPs may be capable of efficiently targeting and treating lung CICs together with cancer cells, and may represent an effective treatment for lung cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C and De Maria R: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15:504–514. 2008. View Article : Google Scholar
4	Kim JJ and Tannock IF: Repopulation of cancer cells during therapy: An important cause of treatment failure. Nat Rev Cancer. 5:516–525. 2005. View Article : Google Scholar : PubMed/NCBI
5	Zakaria N, Satar NA, Abu Halim NH, Ngalim SH, Yusoff NM, Lin J and Yahaya BH: Targeting lung cancer stem cells: Research and clinical impacts. Front Oncol. 7:802017. View Article : Google Scholar : PubMed/NCBI
6	Bertolini G, Roz L, Perego P, Tortoreto M, Fontanella E, Gatti L, Pratesi G, Fabbri A, Andriani F, Tinelli S, et al: Highly tumorigenic lung cancer CD133⁺ cells display stem-like features and are spared by cisplatin treatment. Proc Natl Acad Sci USA. 106:16281–16286. 2009. View Article : Google Scholar
7	Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO, Brooks M, Reinhardt F, Su Y, Polyak K, et al: Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci USA. 108:7950–7955. 2011. View Article : Google Scholar : PubMed/NCBI
8	Gupta PB, Fillmore CM, Jiang G, Shapira SD, Tao K, Kuperwasser C and Lander ES: Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells. Cell. 146:633–644. 2011. View Article : Google Scholar : PubMed/NCBI
9	Iliopoulos D, Hirsch HA, Wang G and Struhl K: Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci USA. 108:1397–1402. 2011. View Article : Google Scholar : PubMed/NCBI
10	Gong Z, Chen D, Xie F, Liu J, Zhang H, Zou H, Yu Y, Chen Y, Sun Z, Wang X, et al: Codelivery of salinomycin and doxorubicin using nanoliposomes for targeting both liver cancer cells and cancer stem cells. Nanomedicine (Lond). 11:2565–2579. 2016. View Article : Google Scholar
11	Xie F, Zhang S, Liu J, Gong Z, Yang K, Zhang H, Lu Y, Zou H, Yu Y, Chen Y, et al: Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro. Nanomedicine (Lond). 11:1831–1846. 2016. View Article : Google Scholar
12	Wang Y: Effects of salinomycin on cancer stem cell in human lung adenocarcinoma A549 cells. Med Chem. 7:106–111. 2011. View Article : Google Scholar : PubMed/NCBI
13	Naujokat C and Steinhart R: Salinomycin as a drug for targeting human cancer initiating cells. J Biomed Biotechnol. 2012:9506582012. View Article : Google Scholar
14	Zhang Y, Zhang Q, Sun J, Liu H and Li Q: The combination therapy of salinomycin and gefitinib using poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells. OncoTargets Ther. 10:5653–5666. 2017. View Article : Google Scholar
15	Ketola K, Hilvo M, Hyötyläinen T, Vuoristo A, Ruskeepää AL, Orešič M, Kallioniemi O and Iljin K: Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 106:99–106. 2012. View Article : Google Scholar : PubMed/NCBI
16	Gao J, Xia Y, Chen H, Yu Y, Song J, Li W, Qian W, Wang H, Dai J and Guo Y: Polymer-lipid hybrid nanoparticles conjugated with anti-EGF receptor antibody for targeted drug delivery to hepatocellular carcinoma. Nanomedicine (Lond). 9:279–293. 2014. View Article : Google Scholar
17	Kapoor DN, Bhatia A, Kaur R, Sharma R, Kaur G and Dhawan S: PLGA: A unique polymer for drug delivery. Ther Deliv. 6:41–58. 2015. View Article : Google Scholar : PubMed/NCBI
18	Gao J, Chen H, Song H, Su X, Niu F, Li W, Li B, Dai J, Wang H and Guo Y: Antibody-targeted immunoliposomes for cancer treatment. Mini Rev Med Chem. 13:2026–2035. 2013. View Article : Google Scholar : PubMed/NCBI
19	Gao J, Feng SS and Guo Y: Antibody engineering promotes nanomedicine for cancer treatment. Nanomedicine (Lond). 5:1141–1145. 2010. View Article : Google Scholar
20	Wang J, Wu Z, Pan G, Ni J, Xie F, Jiang B, Wei L, Gao J and Zhou W: Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147 antibody-conjugated immunoliposomes. Nanomedicine. Oct 16–2017.(Epub ahead of print). pii: S1549-9634(17)30179-X.
21	Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI
22	Sos ML, Koker M, Weir BA, Heynck S, Rabinovsky R, Zander T, Seeger JM, Weiss J, Fischer F, Frommolt P, et al: PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR. Cancer Res. 69:3256–3261. 2009. View Article : Google Scholar : PubMed/NCBI
23	El-Sayed IH, Huang X and El-Sayed MA: Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer. Nano Lett. 5:829–834. 2005. View Article : Google Scholar : PubMed/NCBI
24	Yang L, Mao H, Wang YA, Cao Z, Peng X, Wang X, Duan H, Ni C, Yuan Q, Adams G, et al: Single chain epidermal growth factor receptor antibody conjugated nanoparticles for in vivo tumor targeting and imaging. Small. 5:235–243. 2009. View Article : Google Scholar
25	Cushing BL, Kolesnichenko VL and O'Connor CJ: Recent advances in the liquid-phase syntheses of inorganic nanoparticles. Chem Rev. 104:3893–3946. 2004. View Article : Google Scholar : PubMed/NCBI
26	Allen TM: Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer. 2:750–763. 2002. View Article : Google Scholar : PubMed/NCBI
27	Auffan M, Rose J, Bottero JY, Lowry GV, Jolivet JP and Wiesner MR: Towards a definition of inorganic nanoparticles from an environmental, health and safety perspective. Nat Nanotechnol. 4:634–641. 2009. View Article : Google Scholar : PubMed/NCBI