Enhanced antiproliferative effect of resveratrol in head and neck squamous cell carcinoma using GE11 peptide conjugated liposome

Zheng,Tingting; Feng,Huanhuan; Liu,Li; Peng,Jiao; Xiao,Haitao; Yu,Tao; Zhou,Ziqian; Li,Ying; Zhang,Yuseng; Bai,Xiaohe; Zhao,Simeng; Shi,Yu; Chen,Yun

doi:10.3892/ijmm.2019.4096

Enhanced antiproliferative effect of resveratrol in head and neck squamous cell carcinoma using GE11 peptide conjugated liposome

Authors:
- Tingting Zheng
- Huanhuan Feng
- Li Liu
- Jiao Peng
- Haitao Xiao
- Tao Yu
- Ziqian Zhou
- Ying Li
- Yuseng Zhang
- Xiaohe Bai
- Simeng Zhao
- Yu Shi
- Yun Chen
View Affiliations

Affiliations: Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Shenzhen Peking University‑Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852, P.R. China, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, Guangdong 510852, P.R. China, Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Pharmacy, Health Science Center, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China, Shenzhen Key Laboratory for Neuronal Structural Biology, Shenzhen Peking University‑Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong 510852, P.R. China
Published online on: February 13, 2019 https://doi.org/10.3892/ijmm.2019.4096
Pages: 1635-1642
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study describes the preparation of a dodecapeptide YHWYGYTPQNVI (GE11)‑conjugated liposome bound with polyethylene glycol to enhance the therapeutic effect of resveratrol (RSV) in head and neck cancer cells. The results indicated that (RSV)‑loaded GE11‑conjugated liposomes (RSV‑GL) exhibited a high entrapment efficiency of >95%, with an active drug loading level of 19.5% w/w. Release kinetics revealed that RSV was released in a slow and sustained manner from the RSV‑GL and RSV‑loaded liposome (RSV‑L) nanoparticulate systems. The epidermal growth factor receptor (EGFR)‑overexpressing squamous cell carcinoma HN cells specifically internalized GE11 surface‑conjugated liposome in a manner that was markedly increased compared with that of the non‑targeted carrier. Consistently, RSV‑GL exhibited a significantly increased cytotoxic effect compared with that of the non‑targeted nanoparticles. Notably, RSV‑GL induced significantly increased proportions of early (~60%) and late (~10%) apoptotic cells in head and neck cancer cell populations. To the best of our knowledge, the application and development of EGFR‑targeted peptide‑conjugated liposome system for RSV delivery has not been studied previously in the treatment of head and neck cancer. In addition, RSV‑GL exhibited the greatest antitumor efficacy compared with any other group. RSV‑GL exhibited a 2‑fold decrease in tumor volume compared with the free RSV and a 3‑fold decrease in volume compared with the control. Overall, the nanomedicine strategy described in the present study may potentially advance the chemotherapy‑based treatment of head and neck cancer, with promising applications in other EGFR‑overexpressing tumors.

View Figures

View References

1	Kamangar F, Dores GM and Anderson WF: Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 24:2137–2150. 2006. View Article : Google Scholar : PubMed/NCBI
2	Leemans CR, Braakhuis BJ and Brakenhoff RH: The molecular biology of head and neck cancer. Nat Rev Cancer. 11:9–22. 2011. View Article : Google Scholar
3	Marur S and Forastiere AA: Head and neck cancer: Changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 83:489–501. 2008. View Article : Google Scholar : PubMed/NCBI
4	Vermorken JB and Specenier P: Optimal treatment for recurrent/ metastatic head and neck cancer. Ann Oncol. 21(Suppl 7): vii252–vii261. 2010. View Article : Google Scholar
5	Kuczynski EA, Sargent DJ, Grothey A and Kerbel RS: Drug rechallenge and treatment beyond progressionimplications for drug resistance. Nat Rev Clin Oncol. 10:571–587. 2013. View Article : Google Scholar : PubMed/NCBI
6	Holohan C, Van Schaeybroeck S, Longley DB and Johnston PG: Cancer drug resistance: An evolving paradigm. Nat Rev Cancer. 13:714–726. 2013. View Article : Google Scholar : PubMed/NCBI
7	Yang CS, Landau JM, Huang MT and Newmark HL: Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 21:381–406. 2001. View Article : Google Scholar : PubMed/NCBI
8	Joe AK, Liu H, Suzui M, Vural ME, Xiao D and Weinstein IB: Resveratrol induces growth inhibition, S-phase arrest, apoptosis and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res. 8:893–903. 2002.PubMed/NCBI
9	Jiang H, Zhang L, Kuo J, Kuo K, Gautam SC, Groc L, Rodriguez AI, Koubi D, Hunter TJ, Corcoran GB, et al: Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther. 4:554–561. 2005. View Article : Google Scholar : PubMed/NCBI
10	Buhrmann C, Shayan P, Kraehe P, Popper B, Goel A and Shakibaei M: Resveratrol induces chemosensitization to 5-fluorouracil through up-regulation of intercellular junctions, Epithelial-to-mesenchymal transition and apoptosis in colorectal cancer. Biochem Pharmacol. 98:51–68. 2015. View Article : Google Scholar : PubMed/NCBI
11	Shen M, Wu RX, Zhao L, Li J, Guo HT, Fan R, Cui Y, Wang YM, Yue SQ and Pei JM: Resveratrol attenuates ischemia/reperfusion injury in neonatal cardiomyocytes and its underlying mechanism. PLoS One. 7:e512232012. View Article : Google Scholar
12	Ku CR, Lee HJ, Kim SK, Lee EY, Lee MK and Lee EJ: Resveratrol prevents streptozotocininduced diabetes by inhibiting the apoptosis of pancreatic β-cell and the cleavage of poly (ADP-ribose) polymerase. Endocr J. 59:103–109. 2012. View Article : Google Scholar
13	Walle T, Hsieh F, DeLegge MH, Oatis JE Jr and Walle UK: High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 32:1377–1382. 2004. View Article : Google Scholar : PubMed/NCBI
14	Ramasamy T, Kim JH, Choi JY, Tran TH, Choi HG, Yong CS and Kim JO: pH sensitive polyelectrolyte complex micelles for highly effective combination chemotherapy. J Material Chem B. 2:63242014. View Article : Google Scholar
15	Hare JI, Lammers T, Ashford MB, Puri S, Storm G and Barry ST: Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. Adv Drug Deliv Rev. 108:25–38. 2017. View Article : Google Scholar
16	Sundaramoorthy P, Ramasamy T, Mishra SK, Jeong KY, Yong CS, Kim JO and Kim HM: Engineering of caveolae-specific self-micellizing anticancer lipid nanoparticles to enhance the chemotherapeutic efficacy of oxaliplatin in colorectal cancer cells. Acta Biomater. 42:220–231. 2016. View Article : Google Scholar : PubMed/NCBI
17	Allen TM and Cullis PR: Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliv Rev. 65:36–48. 2013. View Article : Google Scholar
18	Kneidl B, Peller M, Winter G, Lindner LH and Hossann M: Thermosensitive liposomal drug delivery systems: State of the art review. Int J Nanomed. 9:4387–4398. 2014.
19	Mohan A, Narayanan S, Balasubramanian G, Sethuraman S and Krishnan UM: Dual drug loaded nanoliposomal chemotherapy: A promising strategy for treatment of head and neck squamous cell carcinoma. Eur J Pharm Biopharm. 99:73–83. 2016. View Article : Google Scholar
20	Ramasamy T, Ruttala HB, Gupta B, Poudel BK, Choi HG, Yong CS and Kim JO: Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review. J Control Release. 258:226–253. 2017. View Article : Google Scholar : PubMed/NCBI
21	Ramasamy T, Haidar ZS, Tran TH, Choi JY, Choi HG, Yong CS and Kim JO: Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs. Acta Biomaterialia. 10:5116–5127. 2014. View Article : Google Scholar : PubMed/NCBI
22	Rosi NL and Mirkin CA: Nanostructures in biodiagnostics. Chem Rev. 105:1547–1562. 2005. View Article : Google Scholar : PubMed/NCBI
23	Sheng Q and Liu J: The therapeutic potential of targeting the EGFR family in epithelial ovarian cancer. Br J Cancer. 104:1241–1245. 2011. View Article : Google Scholar : PubMed/NCBI
24	Vidal F, de Araujo WM, Cruz AL, Tanaka MN, Viola JP and Morgado-Díaz JA: Lithium reduces tumorigenic potential in response to EGF signaling in human colorectal cancer cells. Int J Oncol. 38:1365–1373. 2011.PubMed/NCBI
25	Acharya S, Dilnawaz F and Sahoo SK: Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. Biomaterials. 30:5737–5750. 2009. View Article : Google Scholar : PubMed/NCBI
26	Chen L, She X, Wang T, He L, Shigdar S, Duan W and Kong L: Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow meso-porous silica nanoparticles. Nanoscale. 7:14080–14092. 2015. View Article : Google Scholar : PubMed/NCBI
27	Kim MW, Jeong HY, Kang SJ, Choi MJ, You YM, Im CS, Lee TS, Song IH, Lee CG, Rhee KJ, et al: Cancer-targeted nucleic acid delivery and quantum dot imaging using EGF receptor aptamer-conjugated lipid nanoparticles. Sci Rep. 7:94742017. View Article : Google Scholar : PubMed/NCBI
28	Li Z, Zhao R, Wu X, Sun Y, Yao M, Li J, Xu Y and Gu J: Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. FASEB J. 19:1978–1985. 2005. View Article : Google Scholar : PubMed/NCBI
29	Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R and Langer R: Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2:751–760. 2007. View Article : Google Scholar
30	Liu D and Auguste DT: Cancer targeted therapeutics: From molecules to drug delivery vehicles. J Control Release. 219:632–643. 2015. View Article : Google Scholar : PubMed/NCBI
31	Huang WC, Chen SH, Chiang WH, Huang CW, Lo CL, Chern CS and Chiu HC: Tumor microenvironment-responsive nanoparticle delivery of chemotherapy for enhanced selective cellular uptake and transportation within tumor. Biomacromolecules. 17:3883–3892. 2016. View Article : Google Scholar : PubMed/NCBI
32	Field LD, Nag OK, Sangtani A, Burns KE and Delehanty JB: The role of nanoparticles in the improvement of systemic anticancer drug delivery. Ther Deliv. 9:527–545. 2018. View Article : Google Scholar : PubMed/NCBI
33	Ruttala HB, Chitrapriya N, Kaliraj K, Ramasamy T, Shin WH, Jeong JH, Kim JR, Ku SK, Choi HG, Yong CS and Kim JO: Facile construction of bioreducible crosslinked polypeptide micelles for enhanced cancer combination therapy. Acta Biomater. 63:135–149. 2017. View Article : Google Scholar : PubMed/NCBI
34	Xu Y, Wang S, Chan HF, Liu Y, Li H, He C, Li Z and Chen M: Triphenylphosphonium-modified poly(ethylene glycol)-poly(ε-caprolactone) micelles for mitochondria- targeted gambogic acid delivery. Int J Pharm. 522:21–33. 2017. View Article : Google Scholar : PubMed/NCBI
35	Sundaramoorthy P, Baskaran R, Mishra SK, Jeong KY, Oh SH, Kyu Yoo B and Kim HM: Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells. Colloids Surf B Biointerfaces. 135:793–801. 2015. View Article : Google Scholar : PubMed/NCBI
36	Ma J, Wu H, Li Y, Liu Z, Liu G, Guo Y, Hou Z, Zhao Q, Chen D and Zhu X: Novel core-interlayer-shell DOX/ZnPc Co-loaded MSNs@ pH-sensitive CaP@PEGylated liposome for enhanced synergetic chemo-photodynamic therapy. Pharm Res. 35:572018. View Article : Google Scholar : PubMed/NCBI
37	Gupta B, Ramasamy T, Poudel BK, Pathak S, Regmi S, Choi JY, Son Y, Thapa RK, Jeong JH, Kim JR, et al: Development of bioactive PEGylated nanostructured platforms for sequential delivery of doxorubicin and imatinib to overcome drug resistance in metastatic tumors. ACS Appl Mater Interfaces. 9:9280–9290. 2017. View Article : Google Scholar : PubMed/NCBI
38	Tyagi P and Subramony JA: Nanotherapeutics in oral and parenteral drug delivery: Key learnings and future outlooks as we think small. J Control Release. 272:159–168. 2018. View Article : Google Scholar