Abstract
To investigate the anti-cancer activity of curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells. Curcumin was incorporated with biopolymeric chitosan, gelatin, and hyaluronan nanoparticles using an electrostatic field system. Characteristics of curcumin-loaded aggregates were examined including size and morphology, incorporation efficiency, stability and in vitro release. Treatment effect on A549 cells were assessed with cell viability assay, apoptosis assay, cell cycle analysis, reactive oxygen species detection, and Western blot. Observation from transmission electron microscopy show that the prepared biopolymeric nanoparticles were approximately 3–4 nm in diameter and that the size of the aggregates increased to approximately 26–55 nm after the incorporation of curcumin with the nanoparticles. The incorporation efficiency of curcumin into the chitosan, gelatin, and hyaluronan nanoparticles was 81, 67, and 78 % respectively. The formation of hyaluronan/curcumin and gelatin/curcumin aggregates seems to improve the stability of curcumin drug. The chitosan/curcumin aggregate has a faster release of curcumin than gelatin/curcumin and hyaluronan/curcumin aggregates. Treatment with chitosan/curcumin, gelatin/curcumin and hyaluronan/curcumin aggregates resulted in higher apoptosis rates of 45, 40 and 32 %, respectively, as compared to pure curcumin (less than 20 %) via Annexin V-FITC/PI analysis. Chitosan/curcumin aggregates induce the highest apoptosis effect (indicated by sub-G1 phase). In summary, chitosan/curcumin, gelatin/curcumin, and hyaluronan/curcumin aggregates represent higher anticancer proliferation properties in A549 cells than curcumin alone that exhibit great potential enhancement by either using fewer drugs or a decreased duration.
Similar content being viewed by others
References
Manju S, Sreenivasan K. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability. J Colloid Interface Sci. 2011;359:318–25.
Sa G, Das T. Anti cancer effects of curcumin: cycle of life and death. Cell Div. 2008;3:14. doi:10.1186/1747-1028-3-14.
Datta R, Halder S, Zhang B. Role of TGF-β signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells. J Cancer Res Clin Oncol. 2013;139:563–72.
Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E. Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett. 2004;208:163–70.
Kizhakkayil J, Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S. Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells. Biochem Biophys Res Commun. 2010;394:476–81.
Tang H, Murphy CJ, Zhang B, Shen Y, Van Kirk EA, Murdoch WJ, Radosz M. Curcumin polymers as anticancer conjugates. Biomaterials. 2010;31:7139–49.
Sanoj Rejinold N, Muthunarayanan M, Divyarani VV, Sreerekha PR, Chennazhi KP, Nair SV, Tamura H, Jayakumar R. Curcumin-loaded biocompatible thermoresponsive polymeric nanoparticles for cancer drug delivery. J Colloid Interface Sci. 2011;360:39–51.
Yallapu MM, Gupta BK, Jaggi M, Chauhan SC. Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. J Colloid Interface Sci. 2010;351:19–29.
Dhule SS, Penfornis P, Frazier T, Walker R, Feldman J, Tan G, He J, Alb A, John V, Pochampally R. Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. Nanomed-Nanotechnol. 2012;8:440–51.
Zhou N, Zan X, Wang Z, Wu H, Yin D, Liao C, Wan Y. Galactosylated chitosan–polycaprolactone nanoparticles for hepatocyte-targeted delivery of curcumin. Carbohydr Polym. 2013;94:420–9.
Ahmed K, Li Y, McClements DJ, Xiao H. Nanoemulsion- and emulsion-based delivery systems for curcumin: encapsulation and release properties. Food Chem. 2012;132:799–807.
Song L, Shen Y, Hou J, Lei L, Guo S, Qian C. Polymeric micelles for parenteral delivery of curcumin: preparation, characterization and in vitro evaluation. Colloids Surf A. 2011;390:25–32.
Yu-Hsien K, Shwu-Jen C, Chin Wen C, Shyh-Ming K, Shu-Ying C, Ru-Ting L. Preparation of bio-polymeric nanoparticles by electrostatic field system. Micro Nano Lett. 2012;7:997–1000.
Gupta AK, Gupta M, Yarwood SJ, Curtis ASG. Effect of cellular uptake of gelatin nanoparticles on adhesion, morphology and cytoskeleton organisation of human fibroblasts. J Control Release. 2004;95:197–207.
Yoshikawa T, Okada N, Oda A, Matsuo K, Matsuo K, Mukai Y, Yoshioka Y, Akagi T, Akashi M, Nakagawa S. Development of amphiphilic γ-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier. Biochem Biophys Res Commun. 2008;366:408–13.
Tang J, Slowing II, Huang Y, Trewyn BG, Hu J, Liu H, et al. Poly(lactic acid)-coated mesoporous silica nanosphere for controlled release of venlafaxine. J Colloid Interface Sci. 2011;360:488–96.
Liu J, Xu L, Liu C, Zhang D, Wang S, Deng Z, Lou W, Xu H, Bai Q, Ma J. Preparation and characterization of cationic curcumin nanoparticles for improvement of cellular uptake. Carbohydr Polym. 2012;90:16–22.
Sun J, Bi C, Chan HM, Sun S, Zhang Q, Zheng Y. Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability. Colloids Surf B. 2013;111:367–75.
Kuo SM, Chiang MY, Lan CW, Niu GC-C, Chang SJ. Evaluation of nanoarchitectured collagen type II molecules on cartilage engineering. J Biomed Mater Res A. 2013;101A:368–77.
Kang PL, Chen CH, Chen SY, Wu YJ, Lin CY, Lin FH, Kuo SM. Nano-sized collagen I molecules enhanced the differentiation of rat mesenchymal stem cells into cardiomyocytes. J Biomed Mater Res A. 2013;101:2808–16.
Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997;15:1867–76.
Priyadarsini KI. Photophysics, photochemistry and photobiology of curcumin: studies from organic solutions, bio-mimetics and living cells. J Photochem Photobiol C. 2009;10:81–95.
Shen L, Ji H-F. The pharmacology of curcumin: is it the degradation products? Trends mol med. 2012;18:138–44.
Weitai W, Shuiqin Z. Hybrid micro-/nanogels for optical sensing and intracellular imaging. Nano Rev. 2010;1:5730. doi:10.3402/nano.v1i0.5730.
López-León T, Carvalho ELS, Seijo B, Ortega-Vinuesa JL, Bastos-González D. Physicochemical characterization of chitosan nanoparticles: electrokinetic and stability behavior. J Colloid Interface Sci. 2005;283:344–51.
Sun J, Bi C, Chan HM, Sun S, Zhang Q, Zheng Y. Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability. Colloids Surf B. 2013;111:367–75.
Huang ZW, Laurent V, Chetouani G, Ljubimova JY, Holler E, Benvegnu T, Loyer P, Cammas-Marion S. New functional degradable and bio-compatible nanoparticles based on poly(malic acid) derivatives for site-specific anti-cancer drug delivery. Int J Pharm. 2012;423:84–92.
Janumyan YM, Sansam CG, Chattopadhyay A, Cheng N, Soucie EL, Penn LZ, Andrews D, Knudson CM, Yang E. Bcl-xL/Bcl-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry. EMBO J. 2003;22:5459–70.
Sun S-H, Huang H-C, Huang C, Lin JK. Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin. Eur J Pharm Sci. 2012;690:22–30.
Punfa W, Yodkeeree S, Pitchakarn P, Ampasavate C, Limtrakul P. Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells. Acta Pharmacol Sin. 2012;33:823–31.
Treuel L, Jiang X, Nienhaus GU. New views on cellular uptake and trafficking of manufactured nanoparticles. J R Soc Interface. 2013;10:20120939. doi:10.1098/rsif.2012.0939.
Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release. 2010;145:182–95.
Acknowledgments
This study was supported by a Grant from the National Science Council, Taiwan (101-2221-E-214-007-MY3).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Benjamin Teong and Chun-Hsu Yao have contributed equally to the present work.
Rights and permissions
About this article
Cite this article
Teong, B., Lin, CY., Chang, SJ. et al. Enhanced anti-cancer activity by curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells. J Mater Sci: Mater Med 26, 49 (2015). https://doi.org/10.1007/s10856-014-5357-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10856-014-5357-3