Abstract
Nanotechnology and drug co-delivery offer a novel avenue in drug delivery research liposome-based co-delivery of anticancer drugs targeting the apoptosis pathway as a promising new approach to treat cancer. In this study, a co-delivery system of liposomes (arsenic trioxide/curcumin) modified with RGD peptide was designed to aim for enhancing the treatment of prostate cancer cells (PC3 cell line). Liposomal co-loaded curcumin and arsenic trioxide modified by RGD peptide (NLPs-RGD-Cur-ATO) were prepared by thin-layer lipid hydration techniques for the treatment of prostate cancer. The stability of the NLPs-RGD-Cur-ATO was evaluated by particle size analysis through dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). The percentage of cytotoxicity and apoptotic effect in PC3 cells treated with NLPs-RGD-Cur-ATO were detected by MTT and Annexin V-FITC (fluorescein isothiocyanate)/PI affinity assay, respectively. The particle size of NLPs-RGD-Cur-ATO was approximately 100 nm, with an encapsulation efficiency of about 99.52% and 70.61%, for ATO and Cur, respectively. Besides, NLPs-RGD-Cur-ATO displayed an enhanced anti-proliferative effect, increased the percentage of apoptotic cells 98 ± 1.85% (p < 0.0001), and significantly reduced EGFR gene expression level (p < 0.001) in the cell line tested. These results indicated that our NLPs-RGD-Cur-ATO co-delivery system was a promising strategy for prostate cancer therapy.
Similar content being viewed by others
Data availability
The datasets generated during the current study are available with the corresponding author(s).
Abbreviations
- RGD:
-
Arginine-glycine-aspartic
- ATO:
-
Arsenic trioxide
- TEM:
-
Transmission electron microscope
- DLS:
-
Dynamic light scattering
- Cur:
-
Curcumin
- NLPs:
-
Nanoliposomes
- PC:
-
Prostate cancer
References
Ahadi M, Naseh V, Salehipour M (2017) The HER-2 as a target gene of Curcumin to protect hepatocytes against the arsenic-induced carcinoma in mice. Iran J Pathol 12(2):158
Bardania H, Shojaosadati SA, Kobarfard F, Dorkoosh F (2016) Optimization of RGD-modified nano-liposomes encapsulating eptifibatide. Iran J Biotechnol 14(2):33
Bardania H, Shojaosadati SA, Kobarfard F, Morshedi D, Aliakbari F, Tahoori MT et al (2019) RGD-modified nano-liposomes encapsulated eptifibatide with proper hemocompatibility and cytotoxicity effect. Iran J Biotechnol 17(2) e2008.
Buhrmann C, Brockmueller A, Mueller A-L, Shayan P, Shakibaei M (2021) Curcumin attenuates environment-derived osteoarthritis by Sox9/NF-kB signaling axis. Int J Mol Sci 22(14):7645
Cackowski FC, Heath EI (2022) Prostate cancer dormancy and recurrence. Cancer Lett 524:103–108
Chow SK, Chan JY, Fung K (2004) Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells. J Cell Biochem 93(1):173–187
Fan J-X, Zeng Y-J, Wu J-W, Li Z-Q, Li Y-M, Zheng R et al (2014) Synergistic killing effect of arsenic trioxide combined with curcumin on KG1a cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 22(5):1267–1272
Fei M, Lu M, Wang Y, Zhao Y, He S, Gao S et al (2009) Arsenic trioxide-induced growth arrest of human hepatocellular carcinoma cells involving FOXO3a expression and localization. Med Oncol 26(2):178–185
Feng T, Wei Y, Lee RJ, Zhao L (2017) Liposomal curcumin and its application in cancer. Int J Nanomed 12:6027
Gandaglia G, Leni R, Bray F, Fleshner N, Freedland SJ, Kibel A et al (2021) Epidemiology and prevention of prostate cancer. Eur Urol Oncol 4(6):877–892
Han D, Ma G, Gao Y, Su Y (2021) Curcumin synergistically enhances the cytotoxicity of arsenic trioxide in U266 cells by increasing arsenic uptake. Evidence-Based Complementary and Alternative Medicine. 2021(3083041)9. https://doi.org/10.1155/2021/3083041
Hu J, Dong Y, Ding L, Dong Y, Wu Z, Wang W et al (2019) Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment. Signal Transduct Target Ther 4(1):1–7
Huang XL, Khan MI, Wang J, Ali R, Ali SW, Kazmi A et al (2021) Role of receptor tyrosine kinases mediated signal transduction pathways in tumor growth and angiogenesis—new insight and futuristic vision. Int J Biol Macromol 180:739–752
Ibrahim S, Tagami T, Kishi T, Ozeki T (2018) Curcumin marinosomes as promising nano-drug delivery system for lung cancer. Int J Pharm 540(1–2):40–49
Jiang S, Han J, Li T, Xin Z, Ma Z, Di W et al (2017) Curcumin as a potential protective compound against cardiac diseases. Pharmacol Res 119:373–383
Jutooru I, Chadalapaka G, Sreevalsan S, Lei P, Barhoumi R, Burghardt R et al (2010) Arsenic trioxide downregulates specificity protein (Sp) transcription factors and inhibits bladder cancer cell and tumor growth. Exp Cell Res 316(13):2174–2188
Khosravani F, Mir H, Mirzaei A, Kobarfard F, Bardania H, Hosseini E (2023) Arsenic trioxide and Erlotinib loaded in RGD‐modified nanoliposomes for targetedcombination delivery to PC3 and PANC‐1 cell lines. Biotechnol Appl Biochem 70(2):811–823
Large DE, Abdelmessih RG, Fink EA, Auguste DT (2021) Liposome composition in drug delivery design, synthesis, characterization, and clinical application. Adv Drug Deliv Rev 176:113851
Li N, Qiu S, Fang Y, Wu J, Li Q (2021) Comparison of linear vs. cyclic RGD pentapeptide interactions with integrin αvβ3 by molecular dynamics simulations. Biology 10(7):688
Liang Y, Zhao J, Zou H, Zhang J, Zhang T (2021) In vitro and in silico evaluation of EGFR targeting activities of curcumin and its derivatives. Food Funct 12(21):10667–10675
Liu J, Liu J, Xu H, Zhang Y, Chu L, Liu Q et al (2014) Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery. Int J Nanomed 9:197–208
Liu Y, Bravo KMC, Liu J (2021a) Targeted liposomal drug delivery: a nanoscience and biophysical perspective. Nanoscale Horizons 6(2):78–94
Liu M, Zheng B, Liu P, Zhang J, Chu X, Dong C et al (2021b) Exploration of the hepatoprotective effect and mechanism of magnesium isoglycyrrhizinate in mice with arsenic trioxide-induced acute liver injury. Mol Med Rep 23(6):1–13
Ludwig BS, Kessler H, Kossatz S, Reuning U (2021) RGD-binding integrins revisited: how recently discovered functions and novel synthetic ligands (re-) shape an ever-evolving field. Cancers 13(7):1711
Mahmoudi R, Ashraf Mirahmadi-Babaheidri S, Delaviz H, Fouani MH, Alipour M, JafariBarmak M et al (2021a) RGD peptide-mediated liposomal curcumin targeted delivery to breast cancer cells. J Biomater Appl 35(7):743–753
Mahmoudi R, Hassandokht F, Ardakani MT, Karimi B, Roustazadeh A, Tarvirdipour S et al (2021b) Intercalation of curcumin into liposomal chemotherapeutic agent augments apoptosis in breast cancer cells. J Biomater Appl 35(8):1005–1018
Margolis E, Brown G, Partin A, Carter B, McKiernan J, Tutrone R et al (2022) Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies. Prostate Cancer Prostatic Dis 25(2):296–301
Mathews V, Binu P, Paul MS, Abhilash M, Manju A, Nair RH (2012) Hepatoprotective efficacy of curcumin against arsenic trioxide toxicity. Asian Pac J Trop Biomed 2(2):S706–S711
Mehta K, Kaur B, Pandey KK, Kaler S, Dhar P (2020) Curcumin supplementation shows modulatory influence on functional and morphological features of hippocampus in mice subjected to arsenic trioxide exposure. Anat Cell Biol 53(3):355
Mirzaei A, Akbari MR, Zadeh SST, Khatami F, Mashhadi R, Aghamir SMK (2022a) Novel combination therapy of prostate cancer cells with arsenic trioxide and flutamide: an in-vitro study. Tissue Cell 74:101684
Mirzaei A, Jahanshahi F, Khatami F, Reis LO, Aghamir SMK (2022b) Human prostate cancer cell epithelial-to-mesenchymal transition as a novel target of arsenic trioxide and curcumin therapeutic approach. Tissue Cell 76:101805
Porębska N, Poźniak M, Matynia A, Żukowska D, Zakrzewska M, Otlewski J et al (2021) Galectins as modulators of receptor tyrosine kinases signaling in health and disease. Cytokine Growth Factor Rev 60:89–106
Qiu Y, Yin X, Li X, Wang Y, Fu Q, Huang R et al (2021) Untangling dual-targeting therapeutic mechanism of epidermal growth factor receptor (EGFR) based on reversed allosteric communication. Pharmaceutics 13(5):747
Rawla P (2019) Epidemiology of prostate cancer. World J Oncol 10(2):63
Rizvi SA, Saleh AM (2018) Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J 26(1):64–70
Sanchez Y, Simon GP, Calvino E, de Blas E, Aller P (2010) Curcumin stimulates reactive oxygen species production and potentiates apoptosis induction by the antitumor drugs arsenic trioxide and lonidamine in human myeloid leukemia cell lines. J Pharmacol Exp Ther 335(1):114–123
Sani S, Messe M, Fuchs Q, Pierrevelcin M, Laquerriere P, Entz-Werle N et al (2021) Biological relevance of RGD-integrin subtype-specific ligands in cancer. ChemBioChem 22(7):1151–1160
Singh SK, Singh S, Lillard JW Jr, Singh R (2017) Drug delivery approaches for breast cancer. Int J Nanomed 12:6205
Starok M, Preira P, Vayssade M, Haupt K, Salome L, Rossi C (2015) EGFR inhibition by curcumin in cancer cells: a dual mode of action. Biomacromol 16(5):1634–1642
SudheshDev S, ZainalAbidin SA, Farghadani R, Othman I, Naidu R (2021) Receptor tyrosine kinases and their signaling pathways as therapeutic targets of curcumin in cancer. Front Pharmacol 12:772510
Sun X-D, Liu X-E, Huang D-S (2012) Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Rep 6(6):1267–1270
Sun M, Wang T, Li L, Li X, Zhai Y, Zhang J et al (2021) The application of inorganic nanoparticles in molecular targeted cancer therapy: EGFR targeting. Front Pharmacol 12:702445
Ulldemolins A, Seras-Franzoso J, Andrade F, Rafael D, Abasolo I, Gener P et al (2021) Perspectives of nano-carrier drug delivery systems to overcome cancer drug resistance in the clinics. Cancer Drug Resist 4(1):44
Uribe ML, Marrocco I, Yarden Y (2021) EGFR in cancer: signaling mechanisms, drugs, and acquired resistance. Cancers 13(11):2748
Wang J, Peng X, Yang D, Guo M, Xu X, Yin F et al (2022a) Bcl-2 hijacks the arsenic trioxide resistance in SH-SY5Y cells. J Cell Mol Med 26(2):563–569
Wang L, Zhu S, Zou C, Kou H, Xu M, Li J (2022b) Preparation and evaluation of the anti-cancer properties of RGD-modified curcumin-loaded chitosan/perfluorohexane nanocapsules in vitro. Heliyon 8(7):e09931
Zeng Y, Weng G, Fan J, Li Z, Wu J, Li Y et al (2016) Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells. Oncol Rep 36(3):1233–1242
Zhan Y, Chen Y, Liu R, Zhang H, Zhang Y (2014) Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling. Arch Pharmacal Res 37(8):1086–1095
Zhang H, Wu Y, Xu X, Chen C, Xue X, Xu B et al (2021) Synthesis characterization of platinum (IV) complex curcumin backboned polyprodrugs: in vitro drug release anticancer activity. Polymers 13(1):67
Zhao L, Yang C, Dou J, Xi Y, Lou H, Zhai G (2015) Development of RGD-functionalized PEG-PLA micelles for delivery of curcumin. J Biomed Nanotechnol 11(3):436–446
Zhen L, Fan D, Yi X, Cao X, Chen D, Wang L (2014) Curcumin inhibits oral squamous cell carcinoma proliferation and invasion via EGFR signaling pathways. Int J Clin Exp Pathol 7(10):6438
Acknowledgements
The present article was extracted from a Master’s thesis written by Fatemeh Amiri.
Funding
This article was financially supported by Yasuj University of Medical Sciences, Yasuj, Iran (Project Number: 4000105).
Author information
Authors and Affiliations
Contributions
FK performed the experiments and analyzed the data; FA, RM, DM, FK, and MA performed the experiments; HB and EH designed the experiments, analyzed the data, and wrote the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical approval
We received full approval for this study from the Ethics Committee of Yasuj University of Medical Sciences (Ethical Code number: IR.YUMS.REC.1400.166).
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Khosravani, F., Amiri, F., Mahmoudi, R. et al. RGD-decorated nanoliposomes for combined delivery of arsenic trioxide and curcumin to prostate cancer cells. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2347–2357 (2024). https://doi.org/10.1007/s00210-023-02752-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-023-02752-7