Advanced bis-MPA hyperbranched dendritic nanocarriers of artemisinin with anticancer potential
Source abstract
Abstract
In this work, a dendritic–linear–dendritic hybrid copolymer based on hyperbranched 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) and linear polyethylene glycol (PEG) chain was employed for the encapsulation of artemisinin, a natural bioactive product with proven anticancer properties. The incorporation of artemisinin in the hyperbranched dendritic nano-scaffolds was accomplished via the “molecular encapsulation process” in the liquid phase. The nano-formulations obtained were evaluated for their structural and textural properties and were characterized by high entrapment efficiency and loading capacity and quantitative in vitro release of their load. They were completely soluble in physiological media and enhanced the solubility of hydrophobic artemisinin. The novel nanomaterials were further biologically evaluated for their degree of anticancer activity in two breast cancer cell lines, namely, MCF-7 and MDA-231, with healthy fibroblasts serving as control. The findings show that the novel nano-formulations maintain the anticancer activity of artemisinin, while they are completely non-toxic towards healthy fibroblasts, demonstrating for the first time the potential of the bis-MPA hyperbranched dendritic scaffolds as carriers and bioavailability enhancers of hydrophobic natural products and pharmacophores.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Synthesis and Characterization of Heterocyclic Compounds · Dendrimers and Hyperbranched Polymers · RNA Interference and Gene Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (60)
Show source-provided references
1. Alexis F, Rhee JW, Richie JP, Radovic-Moreno AF, Langer R, Farokhzad OC (2008) New frontiers in nanotechnology for cancer treatment. Urol Oncol Semin Orig Invest. https://doi.org/10.1016/j.urolonc.2007.03.01710.1016/j.urolonc.2007.03.017 ↗
2. Andrén OCJ, Walter MV, Yang T, Hult A, Malkoch M (2013) Multifunctional poly(ethylene glycol): synthesis, characterization, and potential applications of dendritic–linear–dendritic block copolymer hybrids. Macromolecules 3726−3736. https://doi.org/10.1021/ma400398410.1021/ma4003984 ↗
3. Arvizo RR, Miranda OR, Moyano DF, Walden CA, Giri K, Bhattacharya R, Robertson JD, Rotello VM, Reid JM, Mukherjee P (2011) Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles. Plos One e24374. https://doi.org/10.1371/journal.pone.002437410.1371/journal.pone.0024374 ↗
4. Balan V, Mihai CT, Cojocaru FD, Uritu CM, Dodi G, Botezat D, Gardikiotis I (2019) Vibrational spectroscopy fingerprinting in medicine: from molecular to clinical practice. Materials 2884. https://doi.org/10.3390/ma1218288410.3390/ma12182884 ↗
5. Bharati A and Sabat SC (2010) A spectrophotometric assay for quantification of artemisinin. Talanta 1033–1037. https://doi.org/10.1016/j.talanta.2010.06.01510.1016/j.talanta.2010.06.015 ↗
6. Blanco E, Hsiao A, Mann AP, Landry MG, Meric-Bernstam F, Ferrari M (2011) Nanomedicine in cancer therapy: innovative trends and prospects. Cancer Sci. https://doi.org/10.1111/j.1349-7006.2011.01941.x10.1111/j.1349-7006.2011.01941.x ↗
7. Blaskó G and Cordel GA (1988) Definitive 1H- and 13C-nmr assignments of artemisinin (Qinghaosu). J Nat Prod:1273–1276. https://doi.org/10.1021/np50060a04010.1021/np50060a040 ↗
8. Blazquez AG, Fernandez-Dolon M, Sanchez-Vicente L, Maestre AD, Gomez-San Miguel AB, Alvarez M, Serrano MA, Jansen H, Efferth T, Marin JJ, Romero MR (2013) Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis. Bioorg Med Chem. https://doi.org/10.1016/j.bmc.2013.04.05910.1016/j.bmc.2013.04.059 ↗
9. Charlie-Silva I, Fraceto L, Ferreira Silva de Mélo N (2018) Progress in nano-drug delivery of artemisinin and its derivatives: towards to use in immunomodulatory approaches. Artif Cells Nanomed. Biotechnol. https://doi.org/10.1080/21691401.2018.150573910.1080/21691401.2018.1505739 ↗
10. Choudhary S, Gupta L, Rani S, Dave K, Gupta U (2017) Impact of dendrimers on solubility of hydrophobic drug molecules.FrontPharmacol.https://doi.org/10.3389/fphar.2017.0026110.3389/fphar.2017.00261 ↗
11. Dadgar N, Alavi SE, Esfahani MKM, Akbarzadeh A (2013) Study of toxicity effect of pegylated nanoliposomal artemisinin on breast cancer cell line. Ind J Clin Biochem. https://doi.org/10.1007/s12291-013-0306-310.1007/s12291-013-0306-3 ↗
12. Dadgar N, Esfahani MKM, Torabi S, Alavi SE, Akbarzadeh A (2014) Effects of nanoliposomal and pegylated nanoliposomal artemisinin in treatment of breast cancer. Ind J Clin Biochem. https://doi.org/10.1007/s12291-013-0389-x10.1007/s12291-013-0389-x ↗
13. Datki Z, Juhász A, Gálfi M, Soós K, Papp R, Zádori D, Penke B (2003) Method for measuring neurotoxicity of aggregating polypeptides with the MTT assay on differentiated neuroblastoma cells. Brain Res Bull. https://doi.org/10.1016/j.brainresbull.2003.09.01110.1016/j.brainresbull.2003.09.011 ↗
14. Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJ, Marschall, M (2008) The antiviral activities of artemisinin and artesunate. Clin Infect Dis. https://doi.org/10.1086/59119510.1086/591195 ↗
15. Fröhlich T, Hahn F, Belmudes L, Leidenberger M, Friedrich O, Kappes B, Couté Y, Marschall M, Tsogoeva SB (2018) Synthesis of artemisinin-derived di/tri-mers and dendrimers, investigation of their activity against P. falciparum and cytomegalovirus, and insights into their mechanisms of action. Chem Eur J 24:8103–8113. https://doi.org/10.1002/chem.20180072910.1002/chem.201800729 ↗
16. García-Gallego S, Nyström AM, Malkoch M (2015) Chemistry of multifunctional polymers based on bis-MPA and their cutting-edge applications. Prog Polym Sci. https://doi.org/10.1016/j.progpolymsci.2015.04.00610.1016/j.progpolymsci.2015.04.006 ↗
17. Gharib A, Faezizadeh Z, Mesbah-Namin SAR, Saravani R (2014) Preparation, characterization and in vitro efficacy of magnetic nanoliposomes containing the artemisinin and transferring. Daru 44. https://doi.org/10.1186/2008-2231-22-4410.1186/2008-2231-22-44 ↗
18. Gillies ER, Frechet JM (2005) pH-responsive copolymer assemblies for controlled release of doxorubicin. J Bioconjugate Chem. https://doi.org/10.1021/bc049851c10.1021/bc049851c ↗
19. Gupta S, Tyagi R, Parmar VS, Sharma SK, Haag R (2012) Polyether based amphiphiles for delivery of active components. Polymer. https://doi.org/10.1016/j.polymer.2012.04.04710.1016/j.polymer.2012.04.047 ↗
20. Hed Y, Zhang Y, Andren OCJ, Zeng X, Nystrom AM, Malkoch MJ (2013) Side‐by‐side comparison of dendritic‐linear hybrids and their hyperbranched analogs as micellar carriers of chemotherapeutics. Polym Sci. Part A: Polym Chem. https://doi.org/10.1002/pola.2682510.1002/pola.26825 ↗
21. Hof F, Craig SL, Nuckolls C, Rebek J (2002) Molecular encapsulation. Angew Chem Int Ed. https://doi.org/10.1002/1521-3773(20020503)41:9<1488::aid-anie1488>3.0.co;2-g10.1002/1521-3773(20020503)41:9<1488::aid-anie1488>3.0.co;2-g ↗
22. Irfan M and Seiler, M (2010) Encapsulation using hyperbranched polymers: from research and technologies to emerging applications. Ind Eng Chem Res. https://doi.org/10.1021/ie900216r10.1021/ie900216r ↗
23. Jang J and Oh JH (1999) In situ FT-IR spectroscopic investigation on the microstructure of hyperbranched aliphatic polyesters. Polymer 5985–5992. https://doi.org/10.1016/S0032-3861(98)00824-610.1016/S0032-3861(98)00824-6 ↗
24. Khandare J, Calderon M, Dagia NM, Haag R (2012) Multifunctional dendritic polymers in nanomedicine: opportunities and challenges. Chem Soc Rev 41:2824–2848. https://doi.org/10.1039/c1cs15242d10.1039/c1cs15242d ↗
25. Kojima C, Kono K, Maruyama K, Takagish T (2000) Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs. Bioconjug Chem. https://doi.org/10.1021/bc000058310.1021/bc0000583 ↗
26. Kolhe P, Misra E, Kannan RM, Kannan S, Lieh-Lai M (2003) Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int J Pharm. https://doi.org/10.1016/s0378-5173(03)00225-410.1016/s0378-5173(03)00225-4 ↗
27. Lai H, Singh NP (2006) Oral artemisinin prevents and delays the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in the rat. Cancer Lett. https://doi.org/10.1016/j.canlet.2005.01.01910.1016/j.canlet.2005.01.019 ↗
28. Lai HC, Singh NP, Sasaki T (2012) Development of artemisinin compounds for cancer treatment. Invest New Drugs. https://doi.org/10.1007/s10637-012-9873-z10.1007/s10637-012-9873-z ↗
29. Lawal A, Umar RA, Abubakar MG, Faruk UZ, Wali U (2012) FTIR and UV-Visible spectrophotometric analyses of artemisinin and its derivatives. J Pharm Biomed Sci 6–14
30. Loo CS, Lam NS, Yu D, Su XZ, Lu F (2017) Artemisinin and its derivatives in treating protozoan infections beyond malaria. Pharmacol Res. https://doi.org/10.1016/j.phrs.2016.11.01210.1016/j.phrs.2016.11.012 ↗
31. Lundberg P, Walter MV, Montanez MI, Hult D, Hult A, Nystrom A, Malkoch M (2011) Linear dendritic polymeric amphiphiles with intrinsic biocompatibility: synthesis and characterization to fabrication of micelles and honeycomb membranes. Polym Chem. https://doi.org/10.1039/C0PY00258E10.1039/C0PY00258E ↗
32. Medina SH, El-Sayed MEH (2009) Dendrimers as carriers for delivery of chemotherapeutic agents. Chem Rev. https://doi.org/10.1021/cr900174j10.1021/cr900174j ↗
33. Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today. https://doi.org/10.1016/j.drudis.2010.01.00910.1016/j.drudis.2010.01.009 ↗
34. Michailidou G, Ainali NM, Xanthopoulou E, Nanaki S, Kostoglou M, Koukaras EN, Bikiaris DN (2020) Effect of poly(vinyl alcohol) on nanoencapsulation of budesonide in chitosan nanoparticles via ionic gelation and its improved bioavailability. Polymers (Basel). https://doi.org/10.3390/polym1205110110.3390/polym12051101 ↗
35. Misra SK, Chang HH, Mukherjee P, Tiwari S, Ohoka A, Pan D (2015) Regulating biocompatibility of carbon spheres via defined nanoscale chemistry and a careful selection of surface functionalities. Sci Rep. https://doi.org/10.1038/srep1498610.1038/srep14986 ↗
36. Mohammadifar E, Kharat AN, Adeli M (2015) Polyamidoamine and polyglycerol; their linear, dendritic and linear–dendritic architectures as anticancer drug delivery systems. J Mater Chem B. https://doi.org/10.1039/C4TB02133A10.1039/C4TB02133A ↗
37. Nakase I, Lai H, Singh NP, Sasaki T (2008) Anticancer properties of artemisinin derivatives and their targeted delivery by transferrin conjugation. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2007.09.00310.1016/j.ijpharm.2007.09.003 ↗
38. Namazi H and Adeli M (2005a) Synthesis of barbell-like triblock copolymers, dendritic triazine-block-poly(ethylene glycol)-block-dendritic triazine and investigation of their solution behaviors. Polymer. https://doi.org/10.1016/j.polymer.2005.09.02010.1016/j.polymer.2005.09.020 ↗
39. Namazi H and Adeli M (2005b) Solution proprieties of dendritic triazine/poly (ethylene glycol)/dendritic triazine block copolymers. J Polym Sci Part A: Polym Chem. https://doi.org/10.1002/pola.2047110.1002/pola.20471 ↗
40. Neda D, Dariush N, Mohsen C, Hassan ES, Mohammadreza MS, Ali FA, Akbarzadeh, A (2013) Effect of artemisinin liposome and artemisinin liposome polyethyleneglycol on MCF-7 cell line. Int J Life Sc Bt & Pharm Res 349–355
41. Park JH, Lee S, Kim JH, Park K, Kim K, Kwon IC (2008) Polymeric nanomedicine for cancer therapy. Prog Polym Sci. https://doi.org/10.1016/j.progpolymsci.2007.09.00310.1016/j.progpolymsci.2007.09.003 ↗
42. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. https://doi.org/10.1038/nnano.2007.38710.1038/nnano.2007.387 ↗
43. Polu AR and Kumar R (2011) Impedance spectroscopy and FTIR studies of PEG-based polymer electrolytes. J Chemistry. https://doi.org/10.1155/2011/62879010.1155/2011/628790 ↗
44. Porsch C, Zhang Y, Ducani C, Vilaplana F, Nordstierna L, Nyström AM, Malmström E (2014) Toward unimolecular micelles with tunable dimensions using hyperbranched dendritic-linear polymers. Biomacromolecules. https://doi.org/10.1021/bm500363710.1021/bm5003637 ↗
45. Raffetin A, Bruneel F, Roussel C, Thellier M, Buffet P, Caumes E, Jauréguiberry S (2018) Use of artesunate in non-malarial indications. Med Mal Infect. https://doi.org/10.1016/j.medmal.2018.01.00410.1016/j.medmal.2018.01.004 ↗
46. Ramazani A, Keramati M, Malvandi H, Danafar H, Manjili HK (2018) Preparation and in vivo evaluation of anti-plasmodial properties of artemisinin-loaded PCL-PEG-PCL nanoparticles. Pharm Dev Technol. https://doi.org/10.1080/10837450.2017.137278110.1080/10837450.2017.1372781 ↗
47. Shah SMH, Ullah F, Khan S, Shah SMM, Isreb M (2017) Fabrication and evaluation of smart nanocrystals of artemisinin for antimalarial and antibacterial efficacy. Afr J Tradit Complement Altern Med. https://doi.org/10.21010/ajtcam.v14i1.2710.21010/ajtcam.v14i1.27 ↗
48. Singh NP, Lai HC (2004) Artemisinin induces apoptosis in human cancer cells. Anticancer Res 2277–2280
49. Suberu JO, Romero-Canelón I, Sullivan N, Lapkin AA, Barker GC (2014) Comparative cytotoxicity of artemisinin and cisplatin and their interactions with chlorogenic acids in MCF7 breast cancer cells. Chem Med Chem. https://doi.org/10.1002/cmdc.20140228510.1002/cmdc.201402285 ↗
50. Suttiruengwong S, Rolker J, Smirnova I, Arlt W, Seiler M, Luderitz L, de Diego YP, Jansens PJ (2006) Hyperbranched polymers as drug carriers: microencapsulation and release kinetics. Pharm Dev Technol. https://doi.org/10.1080/1083745050046391910.1080/10837450500463919 ↗
51. Tin AS, Sundar SN, Tran KQ, Park AH, Poidexter KM, Firestone GL (2012) Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1target cell cycle genes. Anticancer Drugs. https://doi.org/10.1097/CAD.0b013e32834f6ea810.1097/CAD.0b013e32834f6ea8 ↗
52. Tomalia, DA, Nixon LS, Hedstrand DM (2020) The role of branch cell symmetry and other critical nanoscale design parameters in the determination of dendrimer encapsulation properties. Biomolecules. https://doi.org/10.3390/biom1004064210.3390/biom10040642 ↗
53. Wang J, Zhang CJ, Chia WN, Loh CC, Li Z, Lee YM, He Y, Yuan LX, Lim TK, Liu M, Liew CX, Lee YQ, Zhang J, Lu N, Lim CT, Hua ZC, Liu B, Shen HM, Tan KS, Lin, Q (2015) Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat Commun. https://doi.org/10.1038/ncomms1011110.1038/ncomms10111 ↗
54. Want MY, Islamuddin M, Chouhan G, Dasgupta AK, Chattopadhyay AP, Afrin, F (2014) Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis. J Colloid Interface Sci:258–26910.1016/j.jcis.2014.06.035 ↗
55. Want MY, Islammudin M, Chouhan G, Ozbak HA, Hemeg HA, Chattopadhyay AP, Afrin F (2017) Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis. Int J Nanomedicine. https://doi.org/10.2147/IJN.S10654810.2147/IJN.S106548 ↗
56. White NJ (1997) Assessment of the pharmacodynamic properties of antimalarial drugs in vivo. Antimicrob. Agents Chemother. https://doi.org/10.1128/AAC.41.7.141310.1128/AAC.41.7.1413 ↗
57. Yu H, Zhao X, Zu Y, Zhang X, Zu B, Zhang X (2012) Preparation and characterization of micronized artemisinin via a rapid expansion of supercritical solutions (RESS) method. Int J Mol Sci. https://doi.org/10.3390/ijms1304506010.3390/ijms13045060 ↗
58. Zeng X, Zhang Y, Wu Z, Lundberg P, Malkoch M, Nyström AM (2012) Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells. J Polym Sci A Polym Chem. https://doi.org/10.1002/pola.2502710.1002/pola.25027 ↗
59. Zhang Y, Xu G, Zhang S, Wang D, Prabha PS, Zuo, Z (2018) Synthesis and anti-glioblastoma effects of artemisinin-isothiocyanate derivatives. Nat Prod Bioprospect. https://doi.org/10.1039/C8RA08162J10.1039/C8RA08162J ↗
60. Zhang Y, Andrén OCJ, Nordström R, Fan Y, Malmsten M, Mongkhontreerat S, Malkoch M (2019) Off-stoichiometric thiol-ene chemistry to dendritic nanogel therapeutics. Adv Funct Mater. https://doi.org/10.1002/adfm.20180669310.1002/adfm.201806693 ↗