Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Cys-BIS-P(VCL-HEA) Nanogels
2.3. Characterization
2.4. Dox Loading
2.5. In Vitro Dox Release from Cys-BIS-P(VCL-HEA)
2.6. Cell Culture
2.7. Cytotoxicity Study
2.8. Cell Uptake and Intracellular Distribution of Dox
3. Results and Discussion
3.1. Preparation and Characterization of Dox-Loaded Cys-BIS-P(VCL-HEA) Nanogels
3.2. Temperature and Redox-Responsive Nature of Cys-BIS-P(VCL-HEA) Nanogels
3.3. In Vitro Drug Release of Dox-Loaded Cys-BIS-P(VCL-HEA) Nanogels
3.4. In Vitro Cytotoxicity
3.5. Cellular Internalization of Dox-Loaded Cys-BIS-P(VCL-HEA) Nanogels
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Seyfried, T.N.; Shelton, L.M. Cancer as a metabolic disease. Nutr. Metab. 2010, 7, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fucic, A.; Gamulin, M.; Ferencic, Z.; Katic, J.; Krayer von Krauss, M.; Bartonova, A.; Merlo, D.F. Environmental exposure to xenoestrogens and oestrogen related cancers: Reproductive system, breast, lung, kidney, pancreas, and brain. J. Environ. Health 2012, 11, S8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adam, R.; Delvart, V.; Pascal, G.; Valeanu, A.; Castaing, D.; Azoulay, D.; Giacchetti, S.; Paule, B.; Kunstlinger, F.; Ghémard, O.; et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Ann. Surg. 2004, 240, 644–657. [Google Scholar] [CrossRef] [PubMed]
- Chang, M.; Zhang, F.; Wei, T.; Zuo, T.; Guan, Y.; Lin, G.; Shao, W. Smart linkers in polymer–drug conjugates for tumor-targeted delivery. J. Drug. Target. 2016, 24, 475–491. [Google Scholar] [CrossRef] [PubMed]
- Steichen, S.D.; Caldorera-Moore, M.; Peppas, N.A. A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics. Eur. J. Pharm. Sci. 2013, 48, 416–427. [Google Scholar] [CrossRef] [Green Version]
- Farokhzad, O.C.; Langer, R. Impact of nanotechnology on drug delivery. ACS Nano 2009, 3, 16–20. [Google Scholar] [CrossRef]
- Cheng, J.; Teply, B.A.; Sherifi, I.; Sung, J.; Luther, G.; Gu, F.X.; Levy-Nissenbaum, E.; Radovic-Moreno, A.F.; Langer, R.; Farokhzad, O.C. Formulation of functionalized PLGA–PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 2007, 28, 869–876. [Google Scholar] [CrossRef] [Green Version]
- Yokoyama, M. Clinical applications of polymeric micelle carrier systems in chemotherapy and image diagnosis of solid tumors. J. Exp. Clin. Med. 2011, 3, 151–158. [Google Scholar] [CrossRef]
- Ahmed, E.M. Hydrogel: Preparation, characterization, and applications: A review. J. Adv. Res. 2015, 6, 105–121. [Google Scholar] [CrossRef] [Green Version]
- Gao, Y.; Xie, J.; Chen, H.; Gu, S.; Zhao, R.; Shao, J.; Jia, L. Nanotechnology-based intelligent drug design for cancer metastasis treatment. Biotechnol. Adv. 2014, 32, 761–777. [Google Scholar] [CrossRef]
- Asadian-Birjand, M.; Sousa-Herves, A.; Steinhilber, D.; Cuggino, J.C.; Calderon, M. Functional nanogels for biomedical applications. Curr. Med. Chem. 2012, 19, 5029–5043. [Google Scholar] [CrossRef] [PubMed]
- Kabanov, A.V.; Vinogradov, S.V. Nanogels as pharmaceutical carriers: Finite networks of infinite capabilities. Angew. Chem. Int. Ed. 2009, 48, 5418–5429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karimi, M.; Ghasemi, A.; Zangabad, P.S.; Rahighi, R.; Basri, S.M.M.; Mirshekari, H.; Amiri, M.; Pishabad, Z.S.; Aslani, A.; Bozorgomid, M.; et al. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem. Soc. Rev. 2016, 45, 1457–1501. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, J.; Dutta, K.; Zhuang, J.; Thayumanavan, S. Cellular-and Subcellular-Targeted Delivery Using a Simple All-in-One Polymeric Nanoassembly. Angew. Chem. Int. Ed. 2020, 59, 23466–23470. [Google Scholar] [CrossRef]
- Mollazadeh, S.; Mackiewicz, M.; Yazdimamaghani, M. Recent advances in the redox-responsive drug delivery nanoplatforms: A chemical structure and physical property perspective. Mater. Sci. Eng. C 2021, 118, 111536. [Google Scholar] [CrossRef]
- Wu, P.; Gao, J.; Prasad, P.; Dutta, K.; Kanjilal, P.; Thayumanavan, S. Influence of Polymer Structure and Architecture on Drug Loading and Redox-Triggered Release. Biomacromolecules 2021, 23, 339–348. [Google Scholar] [CrossRef]
- Lei, B.; Wang, M.; Jiang, Z.; Qi, W.; Su, R.; He, Z. Constructing redox-responsive metal–organic framework nanocarriers for anticancer drug delivery. ACS Appl. Mater. Interfaces 2018, 10, 16698–16706. [Google Scholar] [CrossRef]
- Motamedi, S.; Massoumi, B.; Jaymand, M.; Derakhshankhah, H.; Alizadeh, E. Bioreducible and pH-responsive shell crosslinked polymeric micelles from a star-shaped terpolymer as drug delivery system. Int. J. Polym. Mater. Polym. Biomater. 2020, 71, 481–492. [Google Scholar] [CrossRef]
- Lin, W.; Ma, G.; Kampf, N.; Yuan, Z.; Chen, S. Development of long-circulating zwitterionic cross-linked micelles for active-targeted drug delivery. Biomacromolecules 2016, 17, 2010–2018. [Google Scholar] [CrossRef]
- Meeussen, F.; Nies, E.; Bergmans, H.; Verbrugghe, S.; Goethals, E.; Du Prez, F. Phase behaviour of poly (N-vinyl caprolactam) in water. Polymer 2000, 41, 8597–8602. [Google Scholar] [CrossRef]
- Vihola, H.; Laukkanen, A.; Valtola, L.; Tenhu, H.; Hirvonen, J. Cytotoxicity of thermosensitive polymers poly(N-isopropyl acrylamide), poly(N-vinyl caprolactam) and amphiphilically modified poly(N-vinyl caprolactam). J. Biomater. 2005, 26, 3055–3064. [Google Scholar] [CrossRef] [PubMed]
- Das, D.; Cho, H.; Kim, N.; Pham, T.T.H.; Kim, I.G.; Chung, E.J.; Noh, I. A terpolymeric hydrogel of hyaluronate-hydroxyethyl acrylate-gelatin methacryloyl with tunable properties as biomaterial. Carbohydr. Polym. 2019, 207, 628–639. [Google Scholar] [CrossRef] [PubMed]
- Maciel, D.; Figueira, P.; Xiao, S.; Hu, D.; Shi, X.; Rodrigues, J.; Tomás, H.; Li, Y. Redox-responsive alginate nanogels with enhanced anticancer cytotoxicity. Biomacromolecules 2013, 14, 3140–3146. [Google Scholar] [CrossRef] [PubMed]
- Madhusudana Rao, K.; Mallikarjuna, B.; Krishna Rao, K.S.V.; Siraj, S.; Chowdoji Rao, K.; Subha, M.C.S. Novel thermo/pH sensitive nanogels composed from poly(Nvinylcaprolactam) for controlled release of an anticancer drug. Colloids Surf. B 2013, 102, 891–897. [Google Scholar] [CrossRef] [PubMed]
- Cheng, R.; Feng, F.; Meng, F.; Deng, C.; Feijen, J.; Zhong, Z. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J. Control. Release 2011, 152, 2–12. [Google Scholar] [CrossRef]
- Yang, L.; Wang, Z.; Wang, J.; Jiang, W.; Jiang, X.; Bai, Z.; He, Y.; Jiang, J.; Wang, D.; Yang, L. Doxorubicin conjugated functionalizable carbon dots for nucleus targeted delivery and enhanced therapeutic efficacy. Nanoscale 2016, 8, 6801–6809. [Google Scholar] [CrossRef] [Green Version]
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Rao, K.M.; Suneetha, M.; Kumar, D.V.; Kim, H.J.; Seok, Y.J.; Han, S.S. Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells. Pharmaceutics 2022, 14, 852. https://doi.org/10.3390/pharmaceutics14040852
Rao KM, Suneetha M, Kumar DV, Kim HJ, Seok YJ, Han SS. Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells. Pharmaceutics. 2022; 14(4):852. https://doi.org/10.3390/pharmaceutics14040852
Chicago/Turabian StyleRao, Kummara Madhusudana, Maduru Suneetha, Dachuru Vinay Kumar, Hyeon Jin Kim, Yong Joo Seok, and Sung Soo Han. 2022. "Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells" Pharmaceutics 14, no. 4: 852. https://doi.org/10.3390/pharmaceutics14040852
APA StyleRao, K. M., Suneetha, M., Kumar, D. V., Kim, H. J., Seok, Y. J., & Han, S. S. (2022). Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells. Pharmaceutics, 14(4), 852. https://doi.org/10.3390/pharmaceutics14040852