Thermo-triggered Drug Release from Actively Targeting Polymer Micelles
Abstract
How to deliver the drug to the target area at the right time and at the right concentration is still a challenge in cancer therapy. In this study, we present a facile strategy to control drug release by precisely controlling the thermo-sensitivity of the nanocarriers to the variation of environmental temperature. One type of thermoresponsive Pluronic F127-poly(d,l-lactic acid) (F127-PLA, abbreviated as FP) copolymer micelles was developed and decorated with folate (FA) for active targeting. FP100 micelles assembled from FP with PLA segment having polymerization degree of 100 had a low critical solution temperature of 39.2 °C close to body temperature. At 37 °C, little amount of encapsulated anticancer drug DOX is released from the FP100 micelles, while at a slightly elevated temperature (40 °C), the shrinkage of thermoresponsive segments causes a rapid release of DOX and instantly increases the drug concentration locally. The cytocompatibility analysis and cellular uptake efficiency were characterized with the fibroblast cell line NIH 3T3 and human cervix adenocarcinoma cell line HeLa. The results demonstrate that this copolymer has excellent cytocompatibility, and FA-decorated FP100 micelles present much better efficiency of cellular uptake and higher cytotoxicity to folate receptor (FR)-overexpressed HeLa cells. In particular, under hyperthermia (40 °C) the cytotoxicity of DOX-loaded FA-FP100 micelles against HeLa cells was significantly more obvious than that upon normothermia (37 °C). Therefore, these temperature-responsive micelles have great potential as a drug vehicle for cancer therapy.
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Thermally responsive polymers are a key component of these systems, which are subjected to a distinctive volume phase transition to become hydrophobic or hydrophilic at different temperature.
“Thermally responsive polymers are a key component of these systems, which are subjected to a distinctive volume phase transition to become hydrophobic or hydrophilic at different temperature.171”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [171]
Cites
Nanocarriers as an emerging platform for cancer therapy
Peer, D., Karp, J. M., Hong, S., Farokhzad, O. C., Margalit, R., & Langer, R. (2007) · Nature Nanotechnology · doi:10.1038/nnano.2007.387 · Cited by 8,710 · see citing works
Stimuli-responsive nanocarriers for drug delivery
Mura, S., Nicolas, J., & Couvreur, P. (2013) · Nature Materials · doi:10.1038/nmat3776 · Cited by 6,289 · see citing works
Maeda, H., Nakamura, H., & Fang, J. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.10.002 · Cited by 2,376 · see citing works
Ligand-targeted therapeutics in anticancer therapy
Allen, T. M. (2002) · Nature reviews. Cancer · doi:10.1038/nrc903 · Cited by 1,648 · see citing works
Targeted drug delivery via the folate receptor
Sudimack, J. J., & Lee, R. J. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(99)00062-9 · Cited by 1,477 · see citing works
Fleige, E., Quadir, M., & Haag, R. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.01.020 · Cited by 1,114 · see citing works
Hyperthermia adds to chemotherapy
Issels, R. D. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.07.038 · Cited by 545 · see citing works
Voltage-Responsive Vesicles Based on Orthogonal Assembly of Two Homopolymers
Yan, Q., Yuan, J., Cai, Z., Xin, Y., Kang, Y., & Yin, Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja1027502 · Cited by 511 · see citing works
Polymeric anticancer drugs with pH-controlled activation
Ulbrich, K. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.10.040 · Cited by 495 · see citing works
Feng, L., Yang, X., Shi, X., Tan, X., Peng, R., Wang, J., & Liu, Z. (2013) · Small · doi:10.1002/smll.201202538 · Cited by 414 · see citing works
Self-citationSmart Drug Delivery through DNA/Magnetic Nanoparticle Gates
Ruiz‐Hernández, E., Baeza, A., & Vallet‐Regí, M. (2011) · ACS Nano · doi:10.1021/nn1029229 · Cited by 408 · see citing works
Tumor Redox Heterogeneity‐Responsive Prodrug Nanocapsules for Cancer Chemotherapy
Wang, J., Sun, X., Mao, W., Sun, W., Tang, J., Sui, M., Shen, Y., & Gu, Z. (2013) · Advanced Materials · doi:10.1002/adma.201300929 · Cited by 394 · see citing works
Self-citationZhou, S., Deng, X., & Yang, H. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00207-2 · Cited by 384 · see citing works
Self-citationDuan, X., Xiao, J., Yin, Q., Zhang, Z., Yu, H., Mao, S., & Li, Y. (2013) · ACS Nano · doi:10.1021/nn4010796 · Cited by 378 · see citing works
Zhu, L., Wang, T., Perche, F., Taigind, A., & Torchilin, V. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304987110 · Cited by 360 · see citing works
Krawczyk, P. M., Eppink, B., Essers, J., Stap, J., Rodermond, H. M., Odijk, H., Zelensky, A. N., Chris van, B. R. E. E., Stalpers, L. J. A., Buist, M. R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101053108 · Cited by 353 · see citing works
Martin, G., & Jain, R. K. (1994) · PubMed · Cited by 310 · see citing works
Controlled targeting of liposomal doxorubicin via the folate receptor in vitro
Saul, J. M., Annapragada, A., Natarajan, J. V., & Bellamkonda, R. V. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(03)00295-5 · Cited by 303 · see citing works
pH-triggered intracellular release from actively targeting polymer micelles
Guo, X., Shi, C., Wang, J., Di, S., & Zhou, S. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.02.071 · Cited by 225 · see citing works
Self-citationTumor radiation response enhancement by acoustical stimulation of the vasculature
Czarnota, G. J., Karshafian, R., Burns, P. N., Wong, C. S., Al‐Mahrouki, A., Lee, J. W., Caissie, A. L., Tran, W. T., Kim, C., Furukawa, M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200053109 · Cited by 223 · see citing works
Li, L., ten Hagen, T. L. M., Hossann, M., Süss, R., van Rhoon, G. C., Eggermont, A. M. M., Haemmerich, D., & Koning, G. A. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.03.011 · Cited by 211 · see citing works
Enzyme Sensitive Synthetic Polymer Micelles Based on the Azobenzene Motif
Rao, J., & Khan, A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja407514z · Cited by 207 · see citing works
Fan, N., Cheng, F., Ho, J. A., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203339 · Cited by 203 · see citing works
Ge, H., Hu, Y., Jiang, X., Cheng, D., Yuan, Y., Bi, H., & Yang, C. (2002) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.10143 · Cited by 199 · see citing works
Chen, S., Li, Y., Guo, C., Wang, J., Ma, J., Liang, X., Yang, L., & Liu, H. (2007) · Langmuir · doi:10.1021/la702049d · Cited by 194 · see citing works
Self-citationHubbell, J. A. (2003) · Science · doi:10.1126/science.1083625 · Cited by 186 · see citing works
Functionalized Nanoscale Micelles Improve Drug Delivery for Cancer Therapy in Vitro and in Vivo
Wei, T., Liu, J., Ma, H., Cheng, Q., Huang, Y., Zhao, J., Huo, S., Xue, X., Liang, Z., & Liang, X. (2013) · Nano Letters · doi:10.1021/nl400586t · Cited by 183 · see citing works
Lee, S. H., Choi, S. H., Kim, S. H., et al. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.09.011 · Cited by 166 · see citing works
Yang, H., Mao, H., Wan, Z., Zhu, A., Guo, M., Li, Y., Li, X., Wan, J., Yang, X., Shuai, X., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.08.022 · Cited by 159 · see citing works
Multifunctional Dendronized Peptide Polymer Platform for Safe and Effective siRNA Delivery
Zeng, H., Little, H. C., Tiambeng, T. N., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja400986u · Cited by 148 · see citing works
Relationship Between Microvessel Density and Thermographic Hot Areas in Breast Cancer
Yoshida, S., Nakagawa, S., Yahara, T., Koga, T., Deguchi, H., & Shirouzu, K. (2003) · Surgery Today · doi:10.1007/s005950300055 · Cited by 131 · see citing works
Dong, H., Lei, J., Ju, H., Zhi, F., Wang, H., Guo, W., Zhu, Z., & Yan, F. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201108302 · Cited by 130 · see citing works
Stability and release performance of a series of pegylated copolymeric micelles
Lin, W.-J., Juang, L.-W., & Lin, C.-C. (2003) · Pharmaceutical Research · doi:10.1023/a:1023215320026 · Cited by 125 · see citing works
Dicheva, B. M., ten Hagen, T. L. M., Li, L., et al. (2012) · Nano Letters · doi:10.1021/nl3014154 · Cited by 125 · see citing works
Galactosylated PVDF membrane promotes hepatocyte attachment and functional maintenance
Lu, H., Lim, W. S., Wang, J., et al. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00404-6 · Cited by 89 · see citing works
Self-citationChen, C.-J., Wang, J., Zhao, E.-Y., Gao, L., Feng, Q., Liu, X.-Y., Zhao, Z.-X., Ma, X., Hou, W., Zhang, L., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.056 · Cited by 88 · see citing works
Self-citationFluorescent Multiblock π‐Conjugated Polymer Nanoparticles for In Vivo Tumor Targeting
Ahmed, E., Morton, S. W., Hammond, P. T., & Swager, T. M. (2013) · Advanced Materials · doi:10.1002/adma.201301656 · Cited by 87 · see citing works
Batrakova, E. V., Vinogradov, S. V., Robinson, S. M., et al. (2005) · Bioconjugate Chemistry · doi:10.1021/bc049730c · Cited by 80 · see citing works
Huang, H.-Y., Hu, S.-H., Chian, C.-S., et al. (2012) · Journal of Materials Chemistry · doi:10.1039/c2jm00032f · Cited by 62 · see citing works
Lee, J., Chen, K., Noh, S., Garcia, M. A., Wang, H., Lin, W., Jeong, H., Kong, B. J., Stout, D. B., Cheon, J., et al. (2013) · Angewandte Chemie · doi:10.1002/ange.201207721 · Cited by 62 · see citing works
Thermally Switched Release from Nanoparticle Colloidosomes
Zhou, S., Fan, J., Datta, S. S., et al. (2013) · Advanced Functional Materials · doi:10.1002/adfm.201301030 · Cited by 56 · see citing works
Self-citationIn vivo temperature measurements in brain tumors using proton MR spectroscopy.
Jayasundar, R., & Singh, V. P. (2002) · PubMed · Cited by 45 · see citing works
Chung, M., Chen, K., Liang, H., Liao, Z., Chia, W., Younan Xia, A., & Sung, H. (2012) · Angewandte Chemie · doi:10.1002/ange.201205482 · Cited by 23 · see citing works
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Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00346 · Cited by 3,070 · see citing works
Smart nanoparticles for cancer therapy
Sun, L., Liu, H., Ye, Y., Lei, Y., Islam, R., Tan, S., Tong, R., Miao, Y.-B., & Cai, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01642-x · Cited by 1,073 · see citing works
Karimi, M., Sahandi Zangabad, P., Ghasemi, A., Amiri, M., Bahrami, M., Malekzad, H., Ghahramanzadeh Asl, H., Mahdieh, Z., Bozorgomid, M., Ghasemi, A., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b00371 · Cited by 500 · see citing works
Tang, Z., Zhang, L., Wang, Y., Li, D., Zhong, Z., & Zhou, S. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.06.038 · Cited by 73 · see citing works
Self-citationFolate-conjugated pH-controllable fluorescent nanomicelles acting as tumor targetable drug carriers
Hao, W., Wang, T., Liu, D., Shang, Y., Zhang, J., Xu, S., & Liu, H. (2017) · Microchimica Acta · doi:10.1007/s00604-017-2255-7 · Cited by 9 · see citing works
- Authors
- Guo, X., Li, D., Yang, G., Shi, C., Tang, Z., Wang, J., & Zhou, S.
- Affiliations
- Southwest Jiaotong University (CN)
- Corresponding author
- Zhou, Shaobing
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-05-07
- Volume
- 6
- Issue
- 11
- Pages
- 8549-8559
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2319121321
- Cited by
- 97
- References
- 43
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 13 · 2018: 12 · 2017: 13 · 2016: 12 · 2015: 5 · 2014: 1
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- Pluronic F127, poly(D,L-lactide), folate targeting, drug release, doxorubicin, hyperthermia, folate receptor, anticancer drug delivery, critical solution temperature, cytocompatibility, cellular uptake, HeLa cells
- MeSH terms
- Animals, Doxorubicin, Drug Carriers, HeLa Cells, Humans, Micelles, Polymers, NIH 3T3 Cells, Mice
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