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- In relation to this article, we declare that there is no conflict of interest.
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Received August 8, 2023
Revised September 26, 2023
Accepted September 26, 2023
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This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/3.0) which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright © KIChE. All rights reserved.
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Doxorubicin-loaded PEI-silica Nanoparticles for Cancer Therapy
Chung-Ang University 1PCL, Inc.
dhlee@cau.ac.kr
Korean Chemical Engineering Research, November 2023, 61(4), 570-575(6), 10.9713/kcer.2023.61.4.570 Epub 1 November 2023
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Abstract
Targeted anticancer drug delivery systems are needed to enhance therapeutic efficacy by selectively
delivering drugs to tumor cells while minimizing off-target effects, improving treatment outcomes and reducing toxicity.
In this study, a silica-based nanocarrier capable of targeting drug delivery to cancer cells was developed. First, silica
nanoparticles were synthesized by the Stöber method using the surfactant cetyltrimethylammonium bromide (CTAB).
Increasing the ratio of EtOH in the solvent produced uniformly spherical silica nanoparticles. Washing the nanoparticles
removed unreacted residues, resulting in a non-toxic carrier for drug delivery in cells. Upon surface modification, the
pH-responsive polymer, polyethyleneimine (PEI) exhibited slow doxorubicin release at pH 7.4 and accelerated release at
pH 5.5. By exploiting this feature, we developed a system capable of targeted drug release in the acidic tumor
microenvironment.
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(1990).
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“Effect of Molecular Weight of Regenerated Silk Fibroin onSilk-based Spheres for Drug Delivery,” Korean J. Chemical Engineering,
37, 1732-1742(2020).
24. Bagalkot, V., Farokhzad, O. C., Langer, R. and Jon, S., “An
Aptamer-doxorubicin Physical Conjugate as a Novel Targeted
Drug-delivery Platform,” Angewandte Chemie International Edition,
45(48), 8149-8152B(2006).
25. Sethuraman, V. A., Na, K. and Bae, Y. H., “pH-responsive Sulfonamide/
PEI System for Tumor Specific Gene Delivery: An In
Vitro Study,” Biomacromolecules, 7(1), 64-70(2006).
26. Hu, J., Miura, S., Na, K. and Bae, Y. H., “pH-responsive and
Charge Shielded Cationic Micelle of Poly(L-histidine)-block-
Short Branched PEI for Acidic Cancer Treatment,” J. Controlled
Release, 172(1), 69-76(2013).
27. Xu, B., Zhu, Y.-J., Wang, C.-H., Qiu, C., Sun, J., Yan, Y., Chen,
X., Wang, J.-C. and Zhang, Q., “Improved Cell Transfection of
siRNA by pH-responsive Nanomicelles Self-assembled with
mPEG-b-PHis-b-PEI Copolymers,” ACS Applied Materials & Interfaces,
10(26), 21847-21860(2018).
28. Yang, J., Ryu, W., Lee, S., Kim, K., Choi, M., Lee, Y. and Kim,
B., “Synthesis of pH-Sensitive Hydrogel Nanoparticles in Supercritical
Carbon Dioxide,” Korean Chemical Engineering Research,
47(4), 453-458(2009).
Bagwe, R. P., “Bionanotechnology Based on Silica Nanoparticles,”
Medicinal Research Reviews, 24(5), 621-638(2004).
2. Rahman, I., Vejayakumaran, P., Sipaut, C., Ismail, J. and Chee,
C., “Size-dependent Physicochemical and Optical Properties of
Silica Nanoparticles,” Materials Chemistry and Physics, 114(1),
328-332(2009).
3. Wang, L., Zhao, W. and Tan, W., “Bioconjugated Silica Nanoparticles:
Development and Applications,” Nano Research, 1, 99-115
(2008).
4. Jeelani, P. G., Mulay, P., Venkat, R. and Ramalingam, C., “Multifaceted
Application of Silica Nanoparticles. A Review,” Silicon,
12, 1337-1354(2020).
5. Singh, L. P., Bhattacharyya, S. K., Kumar, R., Mishra, G., Sharma,
U., Singh, G. and Ahalawat, S., “Sol-Gel Processing of Silica
Nanoparticles and Their Applications,” Advances in Colloid and
Interface Science, 214, 17-37(2014).
6. Li, Z.-Z., Wen, L.-X., Shao, L. and Chen, J.-F., “Fabrication of
Porous Hollow Silica Nanoparticles and Their Applications in
Drug Release Control,” J. Controlled Release, 98(2), 245-254
(2004).
7. Bagwe, R. P., Hilliard, L. R. and Tan, W., “Surface Modification of
Silica Nanoparticles to Reduce Aggregation and Nonspecific
Binding,” Langmuir, 22(9), 4357-4362(2006).
8. Wu, S.-H., Hung, Y. and Mou, C.-Y., “Mesoporous Silica Nanoparticles
as Nanocarriers,” Chemical Communications, 47(36), 9972-
9985(2011).
9. Manzano, M. and Vallet-Regí, M., “Mesoporous Silica Nanoparticles
for Drug Delivery,” Advanced Functional Materials, 30(2),
1902634(2020).
10. Wang, Y., Zhao, Q., Han, N., Bai, L., Li, J., Liu, J., Che, E., Hu,
L., Zhang, Q. and Jiang, T., “Mesoporous Silica Nanoparticles
in Drug Delivery and Biomedical Applications,” Nanomedicine:
Nanotechnology, Biology and Medicine, 11(2), 313-327(2015).
11. Mo, R., Sun, Q., Xue, J., Li, N., Li, W., Zhang, C. and Ping, Q.,
“Multistage pH-responsive Liposomes for Mitochondrial-targeted
Anticancer Drug Delivery,” Advanced Materials, 24(27),
3659-3665(2012).
12. Olusanya, T. O., Haj Ahmad, R. R., Ibegbu, D. M., Smith, J. R.,
Elkordy, A. A., “Liposomal Drug Delivery Systems and Anticancer
Drugs,” Molecules, 23(4), 907(2018).
13. Zhang, X., Lin, Y.; Gillies, R. J., “Tumor pH and Its Measurement,”
J. Nuclear Medicine, 51(8), 1167-1170(2010).
14. Gerweck, L. E., Seetharaman, K., “Cellular pH Gradient in Tumor
Versus Normal Tissue: Potential Exploitation for the Treatment
of Cancer,” Cancer Research, 56(6), 1194-1198(1996).
15. Thews, O.; Riemann, A., “Tumor pH and Metastasis: a Malignant
Process Beyond Hypoxia,” Cancer and Metastasis Reviews,
38, 113-129(2019).
16. Koo, H., Lee, H., Lee, S., Min, K. H., Kim, M. S., Lee, D. S.,
Choi, Y., Kwon, I. C., Kim, K., Jeong, S. Y., “In vivo Tumor
Diagnosis and Photodynamic Therapy via Tumoral pH-responsive
Polymeric Micelles,” Chemical Communications, 46(31),
5668-5670(2010).
17. Arcamone, F., Doxorubicin: Anticancer Antibiotics, Elsevier, 2012.
18. Rivankar, S., “An Overview of Doxorubicin Formulations in
Cancer Therapy,” J. Cancer Research and Therapeutics, 10(4),
853-858(2014).
19. Lao, J., Madani, J., Puértolas, T., Álvarez, M., Hernández, A.,
Pazo-Cid, R., Artal, Á., Antón Torres, A., “Liposomal Doxorubicin
in the Treatment of Breast Cancer Patients: A Review,” J.
Drug Delivery, 2013 (2013).
20. Ramalingam, V., Varunkumar, K., Ravikumar, V., Rajaram, R.,
“Target Delivery of Doxorubicin Tethered with PVP Stabilized
Gold Nanoparticles for Effective Treatment of Lung Cancer,”
Scientific Reports, 8(1), 3815(2018).
21. Monk, B. J., Herzog, T. J., Kaye, S. B., Krasner, C. N., Vermorken,
J. B., Muggia, F. M., Pujade-Lauraine, E., Lisyanskaya,
A. S., Makhson, A. N. and Rolski, J., “Trabectedin Plus Pegylated
Liposomal Doxorubicin in Recurrent Ovarian Cancer,” J. Clin
Oncol, 28(19), 3107-14(2010).
22. Olson, R. D., Mushlin, P. S., “Doxorubicin Cardiotoxicity: Analysis
of Prevailing Hypotheses,” The FASEB J., 4(13), 3076-3086
(1990).
23. Wang, Z., Li, X., Cui, Y., Cheng, K., Dong, M. and Liu, L.,
“Effect of Molecular Weight of Regenerated Silk Fibroin onSilk-based Spheres for Drug Delivery,” Korean J. Chemical Engineering,
37, 1732-1742(2020).
24. Bagalkot, V., Farokhzad, O. C., Langer, R. and Jon, S., “An
Aptamer-doxorubicin Physical Conjugate as a Novel Targeted
Drug-delivery Platform,” Angewandte Chemie International Edition,
45(48), 8149-8152B(2006).
25. Sethuraman, V. A., Na, K. and Bae, Y. H., “pH-responsive Sulfonamide/
PEI System for Tumor Specific Gene Delivery: An In
Vitro Study,” Biomacromolecules, 7(1), 64-70(2006).
26. Hu, J., Miura, S., Na, K. and Bae, Y. H., “pH-responsive and
Charge Shielded Cationic Micelle of Poly(L-histidine)-block-
Short Branched PEI for Acidic Cancer Treatment,” J. Controlled
Release, 172(1), 69-76(2013).
27. Xu, B., Zhu, Y.-J., Wang, C.-H., Qiu, C., Sun, J., Yan, Y., Chen,
X., Wang, J.-C. and Zhang, Q., “Improved Cell Transfection of
siRNA by pH-responsive Nanomicelles Self-assembled with
mPEG-b-PHis-b-PEI Copolymers,” ACS Applied Materials & Interfaces,
10(26), 21847-21860(2018).
28. Yang, J., Ryu, W., Lee, S., Kim, K., Choi, M., Lee, Y. and Kim,
B., “Synthesis of pH-Sensitive Hydrogel Nanoparticles in Supercritical
Carbon Dioxide,” Korean Chemical Engineering Research,
47(4), 453-458(2009).
