Abstract
Polyamidoamine (PAMAM) dendrimer is emerging as an effective nanocarrier for delivering anticancer drugs. Still, unmodified PAMAM dendrimer is hardly used in vivo because of unsatisfied drug release, high tendency of interfering with cellular membranes, and rapid clearance by reticuloendothelial system. In this study, low generation polyamidoamine (PAMAM) dendrimer G3.0 is developed and surface modified with methoxypolyethylene glycol (PAMAM G3.0-mPEG) to overcome its limitations. Specifically, PAMAM G3.0 conjugated with mPEG at different ratios are investigated to effectively eliminate its charge-associated toxicity, in which PAMAM G3.0-mPEG- 8 is chosen for oxaliplatin (OX) loading. Results reveal that OX-loaded PAMAM G3.0-mPEG-8 has desirable size, good entrapment efficiency, and sustained release with minimum drug leakage. In addition, Resazurin assay indicates that the toxicity of loaded OX is reduced as compared to free drug but still maintain substantially anticancer activity on HeLa cells, suggesting the potential application of PAMAM G3.0-mPEG-8 for OX delivery in cancer therapy.
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Luong, D., P. Kesharwani, R. Deshmukh, M. C. I. Mohd Amin, U. Gupta, K. Greish, and A. K. Iyer (2016) PEGylated PAMAM dendrimers: Enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. Acta Biomater. 43: 14–29.
Nguyen, C. K., N. Q. Tran, T. P. Nguyen, and D. H. Nguyen (2017) Biocompatible nanomaterials based on dendrimers, hydrogels and hydrogel nanocomposites for use in biomedicine. Adv. Nat. Sci. Nanosci. Nanotechnol. 8: 015001.
Jiang, Y. Y., G. T. Tang, L. H. Zhang, S. Y. Kong, S. J. Zhu, and Y. Y. Pei (2010) PEGylated PAMAM dendrimers as a potential drug delivery carrier: in vitro and in vivo comparative evaluation of covalently conjugated drug and noncovalent drug inclusion complex. J. Drug Target. 18: 389–403.
Tran, N. Q., C. K. Nguyen, and T. P. Nguyen (2013) Dendrimerbased nanocarriers demonstrating a high efficiency for loading and releasing anticancer drugs against cancer cells in vitro and in vivo. Adv. Nat. Sci. Nanosci. Nanotechnol. 4: 045013.
Singh, S. K., G. K. Lohiya, P. P. Limburkar, N. B. Dharbale, and V. K. Mourya (2014) Dendrimer a versatile polymer in drug delivery. Asian J. Pharm. 3: 178–187.
Ho, M. N., L. G. Bach, D. H. Nguyen, C. H. Nguyen, C. K. Nguyen, N. Q. Tran, N. V. Nguyen, and T. T. H. Thi (2019) PEGylated PAMAM dendrimers loading oxaliplatin with prolonged release and high payload without burst effect. Biopolymers. 110: e23272.
Nguyen, D. T. D., L. G. Bach, T. H. Nguyen, M. H. Ho, M. N. Ho, D. H. Nguyen, C. K. Nguyen, and T. T. H. Thi (2019) Preparation and characterization of oxaliplatin drug delivery vehicle based on PEGylated half-generation PAMAM dendrimer. J. Polym. Res. 26: 116.
Liao, H., H. Liu, Y. Li, M. Zhang, H. Tomás, M. Shen, and X. Shi (2014) Antitumor efficacy of doxorubicin encapsulated within PEGylated poly (amidoamine) dendrimers. J. Appl. Polym. Sci. 131: 40358.
Sommerfeld, N. S., M. Hejl, M. H. Klose, E. Schreiber-Brynzak, A. Bileck, S. M. Meier, C. Gerner, M. A. Jakupec, M. Galanski, and B. K. Keppler (2017) Low-generation polyamidoamine dendrimers as drug carriers for platinum (IV) complexes. Eur. J. Inorg. Chem. 2017: 1713–1720.
Nguyen, D. H., J. S. Lee, J. H. Choi, K. M. Park, Y. Lee, and K. D. Park (2016) Hierarchical self-assembly of magnetic nanoclusters for theranostics: tunable size, enhanced magnetic resonance imagability, and controlled and targeted drug delivery. Acta Biomater. 35: 109–117.
Ly, T. U., N. Q. Tran, T. K. Hoang, K. N. Phan, H. N. Truong, and C. K. Nguyen (2013) Pegylated dendrimer and its effect in fluorouracil loading and release for enhancing antitumor activity. J. Biomed. Nanotechnol. 9: 213–220.
Nguyen, T. L., T. H. Nguyen, C. K. Nguyen, and Nguyen (2017) Redox and pH responsive poly (amidoamine) dendrimerheparin conjugates via disulfide linkages for letrozole delivery. Biomed. Res. Int. 2017: 8589212.
Vu, M. T., L. G. Bach, D. C. Nguyen, M. N. Ho, N. H. Nguyen, N. Q. Tran, D. H. Nguyen, C. K. Nguyen, and T. T. H. Thi (2019) Modified carboxyl-terminated PAMAM dendrimers as great cytocompatible nano-based drug delivery system. Int. J. Mol. Sci. 20: 2016.
Ho, M. N., L. G. Bach, T. H. Nguyen, M. H. Ho, D. H. Nguyen, C. K. Nguyen, C. H. Nguyen, N. V. Nguyen, and T. T. H. Thi (2019) PEGylated poly (amidoamine) dendrimers-based drug loading vehicles for delivering carboplatin in treatment of various cancerous cells. J. Nanopart Res. 21: 43.
Hu, W., L. Cheng, L. Cheng, M. Zheng, Q. Lei, Z. Hu, M. Xu, Qiu, and D. Chen (2014) Redox and pH-responsive poly (amidoamine) dendrimer-poly (ethylene glycol) conjugates with disulfide linkages for efficient intracellular drug release. Colloids Sur. B Biointerfaces. 123: 254–263.
Buczkowski, A., D. Waliszewski, P. Urbaniak, and B. Palecz (2016) Study of the interactions of PAMAM G3-NH2 and G3- OH dendrimers with 5-fluorouracil in aqueous solutions. Int. J. Pharm. 505: 1–13.
Shah, N., R. J. Steptoe, and H. S. Parekh (2011) Low-generation asymmetric dendrimers exhibit minimal toxicity and effectively complex DNA. J. Pept. Sci. 17: 470–478.
Yang, H., S. T. Lopina, L. P. DiPersio, and S. P. Schmidt (2008) Stealth dendrimers for drug delivery: correlation between PEGylation, cytocompatibility, and drug payload. J. Mater. Sci. Mater. Med. 19: 1991–1997.
Nguyen, A. K., T. H. Nguyen, B. Q. Bao, L. G. Bach, and D. H. Nguyen (2018) Efficient self-assembly of mPEG end-capped porous silica as a redox-sensitive nanocarrier for controlled doxorubicin delivery. Int. J. Biomater. 2018: 1575438.
Kim, Y., A. M. Klutz, and K. A. Jacobson (2008) Systematic investigation of polyamidoamine dendrimers surface-modified with poly (ethylene glycol) for drug delivery applications: synthesis, characterization, and evaluation of cytotoxicity. Bioconjugate Chem. 19: 1660–1672.
Sarkar, K. and H. Yang (2008) Encapsulation and extended release of anti-cancer anastrozole by stealth nanoparticles. Drug Deliv. 15: 343–346.
Tran, D. H. N., T. H. Nguyen, T. N. N. Vo, L. P. T. Pham, D. M. H. Vo, C. K. Nguyen, L. G. Bach, and D. H. Nguyen (2019) Selfassembled poly (ethylene glycol) methyl ether-grafted gelatin nanogels for efficient delivery of curcumin in cancer treatment. J. Appl. Polym. Sci. 136: 47544.
Jevprasesphant, R., J. Penny, R. Jalal, D. Attwood, N. B. McKeown, and A. D’Emanuele (2003) The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int. J. Pharm. 252: 263–266.
Karthikeyan, R., O. S. Koushik, and V. P. Kumar (2016) Surface modification of cationic dendrimers eases drug delivery of anticancer drugs. Nano Sci. Nano Technol. 10: 109.
Dilruba, S. and G. V. Kalayda (2016) Platinum-based drugs: past, present and future. Cancer Chemother. Pharmacol. 77: 1103–1124.
Marques, M. P. M. (2013) Platinum and palladium polyamine complexes as anticancer agents: the structural factor. Int. Sch. Res. Notices. 2013: 287353.
Lee, P. C., C. Y. Lin, C. L. Peng, and M. J. Shieh (2016) Development of a controlled-release drug delivery system by encapsulating oxaliplatin into SPIO/MWNT nanoparticles for effective colon cancer therapy and magnetic resonance imaging. Biomater. Sci. 4: 1742–1753.
Vivek, R., R. Thangam, V. Nipunbabu, T. Ponraj, and S. Kannan (2014) Oxaliplatin-chitosan nanoparticles induced intrinsic apoptotic signaling pathway: A “smart” drug delivery system to breast cancer cell therapy. Int. J. Biol. Macromol. 65: 289–297.
Dutta, R. K. and S. Sahu (2012) Development of oxaliplatin encapsulated in magnetic nanocarriers of pectin as a potential targeted drug delivery for cancer therapy. Results Pharma Sci. 2: 38–45.
Brown, S. D., P. Nativo, J. A. Smith, D. Stirling, P. R. Edwards, B. Venugopal, D. J. Flint, J. A. Plumb, D. Graham, and N. J. Wheate (2010) Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. J. Am. Chem. Soc. 132: 4678–4684.
Thanh, V. M., T. H. Nguyen, T. V. Tran, U. P. Ngoc, M. N. Ho, T. T. Nguyen, Y. N. T. Chau, V. T. Le, N. Q. Tran, C. K. Nguyen, and D. H. Nguyen (2018) Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release. Mater. Sci. Eng. C Mater. Biol. Appl. 82: 291–298.
Tong, N. A. N., T. H. Nguyen, D. H. Nguyen, C. K. Nguyen, and N. Q. Tran (2015) Preparation of the cationic dendrimer-based hydrogels for controlled heparin release. J. Macromol. Sci. Part A. 52: 830–837.
Bao, B. Q., N. H. Le, D. H. T. Nguyen, T. V. Tran, L. P. T. Pham, L. G. Bach, H. M. Ho, T. H. Nguyen, and D. H. Nguyen (2018) Evolution and present scenario of multifunctionalized mesoporous nanosilica platform: A mini review. Mater. Sci. Eng. C Mater. Biol. Appl. 91: 912–928.
Thi, T. N. L., T. H. Nguyen, D. Q. Hoang, T. V. Tran, N. T. Nguyen, and D. H. Nguyen (2017) Development of new magnetic nanoparticles: Oligochitosan obtained by γ-rays and- coated Fe3O4 nanoparticles. Appl. Surf. Sci. 422: 863–868.
Nguyen, D. H., J. W. Bae, J. H. Choi, J. S. Lee, and K. D. Park (2013) Bioreducible cross-linked Pluronic micelles: pH-triggered release of doxorubicin and folate-mediated cellular uptake. J. Bioact. Compat. Polym. 28: 341–354.
Thi, T. T. H., D. H. N. Tran, L. G. Bach, Q. H. Vu, D. C. Nguyen, K. D. Park, and D. H. Nguyen (2019) Functional magnetic coreshell system-based iron oxide nanoparticle coated with biocompatible copolymer for anticancer drug delivery. Pharmaceutics. 11: e120.
Babu, A., J. Periasamy, A. Gunasekaran, G. Kumaresan, S. Naicker, P. Gunasekaran, and R. Murugesan (2013) Polyethylene glycol-modified gelatin/polylactic acid nanoparticles for enhanced photodynamic efficacy of a hypocrellin derivative in vitro. J. Biomed. Nanotechnol. 9: 177–192.
Narmani, A., M. Kamali, B. Amini, A. Salimi, and Y. Panahi (2018) Targeting delivery of oxaliplatin with smart PEG-modified PAMAM G4 to colorectal cell line: In vitro studies. Process Biochem. 69: 178–187.
Ebrahimifar, M., A. Nili-Ahmadabadi, A. Akbarzadeh, H. E. Shahemabadi, M. Hasanzadegan, H. Moradi-Sardareh, H. Madadizadeh, and J. Rezaee-diyan (2017) Preparation, characterization and cytotoxic effects of pegylated nanoliposomal containing carboplatin on ovarian cancer cell lines. Indian J. Clin. Biochem. 32: 230–234.
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Effective Elimination of Charge-associated Toxicity of Low Generation Polyamidoamine Dendrimer Eases Drug Delivery of Oxaliplatin
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Do, V.M.H., Bach, L.G., Tran, DH.N. et al. Effective Elimination of Charge-associated Toxicity of Low Generation Polyamidoamine Dendrimer Eases Drug Delivery of Oxaliplatin. Biotechnol Bioproc E 25, 224–234 (2020). https://doi.org/10.1007/s12257-019-0047-0
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DOI: https://doi.org/10.1007/s12257-019-0047-0