Abstract
Here, chitosan/gelatin hybrid nanogel containing gold nanoparticles (CS/AuNPs@Gel) was prepared as an efficient enzyme-responsive carrier for doxorubicin (DOX) delivery. Nanogel was fabricated via ionic crosslinking of CS/AuNPs in the presence of gelatin as an enzyme-responsive moiety. The physicochemical properties of the final compounds were investigated by FT-IR, DLS, TEM, and UV–Vis spectroscopy. The mean size of the prepared CS/AuNPs and CS/AuNPs@Gel was around 83 nm and 119.3 nm with a zeta potential of 83.9 mV and 31.9 mV, respectively. The loading efficiency of DOX in the CS/AuNPs@Gel nanogel was about 56% and DOX was released from the nanogel in an enzyme-responsive manner. The cytotoxic assay on the MCF-7 cells revealed the nontoxicity of free nanogel, the effectiveness of drug-loaded nanogel (DN), and DN in the presence of an enzyme compared with the free DOX.
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References
Jacob J, Haponiuk JT, Thomas S, Gopi S (2018) Biopolymer based nanomaterials in drug delivery systems: a review. Mater Today Chem 9:43–55. https://doi.org/10.1016/j.mtchem.2018.05.002
Ranjbar-Navazi Z, Fathi M, Abdolahinia ED, Omidi Y, Davaran S (2021) MUC-1 aptamer conjugated InP/ZnS quantum dots/nanohydrogel fluorescent composite for mitochondria-mediated apoptosis in MCF-7 cells. Mater Sci Eng C 118:111469. https://doi.org/10.1016/j.msec.2020.111469
Kukoyi AR (2016) Economic impacts of natural polymers. Natural Polymers 339–362 (Springer)
Fathi M, Safary A, Barar J (2020) Therapeutic impacts of enzyme-responsive smart nanobiosystems. BioImpacts: BI 10(1):1. https://doi.org/10.15171/bi.2020.01
Khiavi MA, Safary A, Aghanejad A, Barar J, Rasta SH, Golchin A et al (2019) Enzyme-conjugated gold nanoparticles for combined enzyme and photothermal therapy of colon cancer cells. Colloids Surf A Physicochem Eng Asp 572:333–344. https://doi.org/10.1016/j.colsurfa.2019.04.019
Hu Q, Katti PS, Gu Z (2014) Enzyme-responsive nanomaterials for controlled drug delivery. Nanoscale 6(21):12273–12286. https://doi.org/10.1039/C4NR04249B
Das SS, Bharadwaj P, Bilal M, Barani M, Rahdar A, Taboada P et al (2020) Stimuli-responsive polymeric nanocarriers for drug delivery, imaging, and theragnosis. Polymers 12(6):1397. https://doi.org/10.3390/polym12061397
Lu J, Li Z, Zink JI, Tamanoi F (2012) In vivo tumor suppression efficacy of mesoporous silica nanoparticles-based drug-delivery system: enhanced efficacy by folate modification. Nanomed: Nanotechnol Biol Med 8(2):212–220. https://doi.org/10.1016/j.nano.2011.06.002
Wang M, Thanou M (2010) Targeting nanoparticles to cancer. Pharmacol Res 62(2):90–99. https://doi.org/10.1016/j.phrs.2010.03.005
Banu H, Sethi DK, Edgar A, Sheriff A, Rayees N, Renuka N et al (2015) Doxorubicin loaded polymeric gold nanoparticles targeted to human folate receptor upon laser photothermal therapy potentiates chemotherapy in breast cancer cell lines. J Photochem Photobiol B Biol 149:116–128. https://doi.org/10.1016/j.jphotobiol.2015.05.008
Essawy MM, El-Sheikh SM, Raslan HS, Ramadan HS, Kang B, Talaat IM et al (2021) Function of gold nanoparticles in oral cancer beyond drug delivery: implications in cell apoptosis. Oral Dis 27(2):251–265. https://doi.org/10.1111/odi.13551
Suri SS, Fenniri H, Singh B (2007) Nanotechnology-based drug delivery systems. J Occup Med Toxicol 2(1):1–6. https://doi.org/10.1186/1745-6673-2-16
Khodashenas B, Ardjmand M, Rad A, Esfahani M (2021) Gelatin-coated gold nanoparticles as an effective pH-sensitive methotrexate drug delivery system for breast cancer treatment. Mater Today Chem 20:100474. https://doi.org/10.1016/j.mtchem.2021.100474
Grobmyer SR, Zhou G, Gutwein LG, Iwakuma N, Sharma P, Hochwald SN (2012) Nanoparticle delivery for metastatic breast cancer. Nanomed Nanotechnol Biol Med 8:S21–S30. https://doi.org/10.1016/j.nano.2012.05.011
Arami S, Mahdavi M, Rashidi MR, Fathi M, Hejazi M-s, Samadi N (2016) Novel polyacrylate-based cationic nanoparticles for survivin siRNA delivery combined with mitoxantrone for treatment of breast cancer. Biologicals 44(6):487–496. https://doi.org/10.1016/j.biologicals.2016.09.005
Gobi R, Ravichandiran P, Babu RS, Yoo DJ (2021) Biopolymer and synthetic polymer-based nanocomposites in wound dressing applications: a review. Polymers 13(12):1962. https://doi.org/10.3390/polym13121962
Yang YY, Wang Y, Powell R, Chan P (2006) Polymeric core-shell nanoparticles for therapeutics. Clin Exp Pharmacol Physiol 33(5–6):557–562. https://doi.org/10.1111/j.1440-1681.2006.04408.x
Coelho JF (2014) Drug delivery systems: advanced technologies potentially applicable in personalised treatment, educational measures. EPMA Journal: Springer; p 1–1
Fathi M, Abdolahinia ED, Barar J, Omidi Y (2020) Smart stimuli-responsive biopolymeric nanomedicines for targeted therapy of solid tumors. Nanomedicine 15(22):2171–2200. https://doi.org/10.2217/nnm-2020-0146
Caló E, Khutoryanskiy VV (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J 65:252–267. https://doi.org/10.1016/j.eurpolymj.2014.11.024
Fathi M, Zangabad PS, Majidi S, Barar J, Erfan-Niya H, Omidi Y (2017) Stimuli-responsive chitosan-based nanocarriers for cancer therapy. BioImpacts: BI 7(4):269. https://doi.org/10.15171/bi.2017.32
Yousefi M, Orojzadeh P, Jafari SM (2019) Nanoencapsulation of food ingredients by dendrimers. Biopolymer nanostructures for food encapsulation purposes. Elsevier; p. 607-625
Mu J, Lin J, Huang P, Chen X (2018) Development of endogenous enzyme-responsive nanomaterials for theranostics. Chem Soc Rev 47(15):5554–5573. https://doi.org/10.1039/C7CS00663B
Safary A, Moniri R, Hamzeh-Mivehroud M, Dastmalchi S (2019) Highly efficient novel recombinant L-asparaginase with no glutaminase activity from a new halo-thermotolerant Bacillus strain. BioImpacts: BI 9(1):15. https://doi.org/10.15171/bi.2019.03
Shahriari M, Zahiri M, Abnous K, Taghdisi SM, Ramezani M, Alibolandi M (2019) Enzyme responsive drug delivery systems in cancer treatment. J Control Release 308:172–189. https://doi.org/10.1016/j.jconrel.2019.07.004
Cheng N-C, Lin W-J, Ling T-Y, Young T-H (2017) Sustained release of adipose-derived stem cells by thermosensitive chitosan/gelatin hydrogel for therapeutic angiogenesis. Acta Biomater 51:258–267. https://doi.org/10.1016/j.actbio.2017.01.060
Nezhad-Mokhtari P, Akrami-Hasan-Kohal M, Ghorbani M (2020) An injectable chitosan-based hydrogel scaffold containing gold nanoparticles for tissue engineering applications. Int J Biol Macromol 154:198–205. https://doi.org/10.1016/j.ijbiomac.2020.03.112
Fathi M, Zangabad PS, Barar J, Aghanejad A, Erfan-Niya H, Omidi Y (2018) Thermo-sensitive chitosan copolymer-gold hybrid nanoparticles as a nanocarrier for delivery of erlotinib. Int J Biol Macromol 106:266–276. https://doi.org/10.1016/j.ijbiomac.2017.08.020
Chidambaram N, Burgess D (1999) A novel in vitro release method for submicron-sized dispersed systems. AAPS Pharm Sci 1(3):32–40. https://doi.org/10.1208/ps010311
Baei P, Jalili-Firoozinezhad S, Rajabi-Zeleti S, Tafazzoli-Shadpour M, Baharvand H, Aghdami N (2016) Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering. Mater Sci Eng C 63:131–141. https://doi.org/10.1016/j.msec.2016.02.056
Peng J, Wang X, Lou T (2020) Preparation of chitosan/gelatin composite foam with ternary solvents of dioxane/acetic acid/water and its water absorption capacity. Polym Bull 77(10):5227–5244. https://doi.org/10.1007/s00289-019-03016-2
Ferreira Tomaz A, Sobral de Carvalho SM, Cardoso Barbosa R, L. Silva SM, Sabino Gutierrez MA, B. de Lima AG, et al (2018) Ionically crosslinked chitosan membranes used as drug carriers for cancer therapy application. Materials 11(10):2051. https://doi.org/10.2147/IJN.S232350
Conde J, Dias JT, Grazú V, Moros M, Baptista PV, de la Fuente JM (2014) Revisiting 30 years of biofunctionalization and surface chemistry of inorganic nanoparticles for nanomedicine. Front Chem 2:48. https://doi.org/10.3389/fchem.2014.00048
Corbierre MK, Cameron NS, Sutton M, Mochrie SG, Lurio LB, Rühm A et al (2001) Polymer-stabilized gold nanoparticles and their incorporation into polymer matrices. J Am Chem Soc 123(42):10411–10412. https://doi.org/10.1021/ja0166287
Chen AL, Hu YS, Jackson MA, Lin AY, Young JK, Langsner RJ et al (2014) Quantifying spectral changes experienced by plasmonic nanoparticles in a cellular environment to inform biomedical nanoparticle design. Nanoscale Res Lett 9(1):1–16. https://doi.org/10.1186/1556-276X-9-454
Zhang X, Hu Y, Liu R, Sun J, Fang S (2015) Thermosensitive gold nanoparticles based on star-shaped poly (N-isopropylacrylamide) with a cubic silsesquioxane core. Macromol Res 23(3):227–230. https://doi.org/10.1007/s13233-015-3038-9
Salem DS, Sliem MA, El-Sesy M, Shouman SA, Badr Y (2018) Improved chemo-photothermal therapy of hepatocellular carcinoma using chitosan-coated gold nanoparticles. J Photochem Photobiol B Biol 182:92–99. https://doi.org/10.1016/j.jphotobiol.2018.03.024
Jiang X, Århammar C, Liu P, Zhao J, Ahuja R (2013) The R3-carbon allotrope: a pathway towards glassy carbon under high pressure. Sci Rep 3(1):1–9. https://doi.org/10.1038/srep01877
Xue P, Cheong KK, Wu Y, Kang Y (2015) An in-vitro study of enzyme-responsive Prussian blue nanoparticles for combined tumor chemotherapy and photothermal therapy. Colloids Surf B 125:277–283. https://doi.org/10.1016/j.colsurfb.2014.10.059
Borse S, Joshi S, Khan A (2015) Enhanced in vitro cytotoxicity and cellular uptake of DNA bases functionalized gold nanoparticles in HeLa cell lines. RSC Adv 5(18):13402–13410. https://doi.org/10.1039/C4RA15356A
Acknowledgements
Also, the authors are thankful to the Research Center for Pharmaceutical Nanotechnology at Tabriz University of Medical Sciences and Faculty of Chemical and Petroleum Engineering, University of Tabriz, for the technical supports.
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The study was financially supported by the Research Vice-Chancellor of Tabriz University of Medical Sciences (Grant # 66349).
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Aslzad, S., Heydari, P., Abdolahinia, E.D. et al. Chitosan/gelatin hybrid nanogel containing doxorubicin as enzyme-responsive drug delivery system for breast cancer treatment. Colloid Polym Sci 301, 273–281 (2023). https://doi.org/10.1007/s00396-023-05066-5
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DOI: https://doi.org/10.1007/s00396-023-05066-5