Lipoyl Ester Terminated Star PLGA as a Simple and Smart Material for Controlled Drug Delivery Application
Abstract
PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs). Interestingly, sPLGA XNPs obtained in the presence of 23.0 wt % PEG-PDLLA displayed a small hydrodynamic size of 73 ± 1.2 nm, high stability against dilution and 10% serum, while fast destabilization under a reductive environment. Moreover, sPLGA XNPs achieved efficient loading of lipophilic anticancer drug model, doxorubicin (DOX), at a theoretical drug loading content of 13.3 wt %, giving DOX-loaded sPLGA XNPs with reduced drug leakage under physiological conditions as well as significantly accelerated drug release under 10 mM glutathione condition compared with both linear and star PLGA controls (denoted as lPLGA NPs and sPLGA NPs, respectively). Confocal microscopy and flow cytometry displayed obviously stronger DOX fluorescence in B16F10 melanoma cells treated with DOX-loaded sPLGA XNPs than with lPLGA and sPLGA counterparts. MTT assays revealed that DOX-sPLGA XNPs caused 2.4- and 4.2-fold higher antitumor activity toward B16F10 cells than DOX-sPLGA NPs and DOX-lPLGA NPs, respectively. Notably, in vivo pharmacokinetics studies showed prolonged circulation time and significantly improved AUC for DOX-sPLGA XNPs over lPLGA NPs control. Hence, lipoyl ester terminated star PLGA emerges as a simple and smart material for better-controlled anticancer drug delivery.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An increase in polylactic acid content leads to less water absorption, thus reducing the rate of degradation.
“The increase in polylactic acid content leads to less water absorption, thus reduces the rate of degradation.20”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [20]
Cites
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
PLGA-based nanoparticles: An overview of biomedical applications
Danhier, F., Ansorena, E., Silva, J. M., Coco, R., Breton, A. L., & Véronique Préat, A. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.01.043 · Cited by 3,884 · see citing works
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
Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery
Fang, R. H., Hu, C. J., Luk, B. T., Gao, W., Copp, J. A., Tai, Y., O’Connor, D. E., & Zhang, L. (2014) · Nano Letters · doi:10.1021/nl500618u · Cited by 1,509 · see citing works
Hrkach, J. S., Hoff, D. D. V., Ali, M. M., Andrianova, E. A., Auer, J., Campbell, T., Witt, D. D., Figa, M. A., Figueiredo, M., Horhota, A. T., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003651 · Cited by 1,147 · 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
Advanced materials and processing for drug delivery: The past and the future
Zhang, Y., Chan, H. F., & Leong, K. W. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.10.003 · Cited by 1,008 · see citing works
Polymer-encapsulated organic nanoparticles for fluorescence and photoacoustic imaging
Li, K., & Liu, B. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00014e · Cited by 989 · see citing works
Biodegradation and biocompatibility of PLA and PLGA microspheres
Anderson, J., & Shive, M. S. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.004 · Cited by 814 · see citing works
Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation
Danhier, F., Lecouturier, N., Vroman, B., Jérôme, C., Marchand‐Brynaert, J., Féron, O., & Véronique Préat, A. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.09.086 · Cited by 617 · see citing works
Synthetic biopolymer nanocomposites for tissue engineering scaffolds
Okamoto, M., & John, B. (2013) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2013.06.001 · Cited by 509 · see citing works
Li, Y., Zhu, L., Liu, Z., Cheng, R., Meng, F., Cui, J., Ji, S., & Zhong, Z. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200904260 · Cited by 451 · see citing works
Self-citationPolymeric nanostructured materials for biomedical applications
Tang, Z., He, C., Tian, H., Ding, J., Hsiao, B. S., Chu, B., & Chen, X. (2016) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2016.05.005 · Cited by 364 · see citing works
Hoff, D. D. V., Mita, M. M., Ramanathan, R. K., Weiss, G. J., Mita, A. C., LoRusso, P. M., Burris, H. A., Hart, L. L., Low, S. C., Parsons, D. M., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2548 · Cited by 289 · see citing works
Zhong, Y., Zhang, J., Cheng, R., Deng, C., Meng, F., Xie, F., & Zhong, Z. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.01.012 · Cited by 285 · see citing works
Self-citationPLGA nanoparticles loaded with host defense peptide LL37 promote wound healing
Chereddy, K. K., Her, C.-H., Comune, M., Moia, C., Lopes, A., Porporato, P. E., Vanacker, J., Lam, M. C., Steinstraesser, L., Sonveaux, P., et al. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.08.016 · Cited by 268 · see citing works
Stimuli-Responsive Programmed Specific Targeting in Nanomedicine
Wang, S., Huang, P., & Chen, X. S. (2016) · ACS Nano · doi:10.1021/acsnano.6b00870 · Cited by 252 · see citing works
Self‐Assembled Smart Nanocarriers for Targeted Drug Delivery
Cui, W., Li, J., & Decher, G. (2015) · Advanced Materials · doi:10.1002/adma.201502479 · Cited by 235 · see citing works
Zhu, H., Chen, H., Zeng, X., Wang, Z., Zhang, X., Wu, Y., Gao, Y., Zhang, J., Liu, K., Liu, R., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.086 · Cited by 233 · see citing works
Fornaguera, C., Dols-Pérez, A., Calderó, G., García, M. J. N., Camarasa, J., & Solans, C. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.06.002 · Cited by 221 · see citing works
Wang, H., Agarwal, P., Zhao, S., Xu, R. X., Yu, J., Lu, X., & He, X. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.08.048 · Cited by 217 · see citing works
Nanoscale theranostics for physical stimulus-responsive cancer therapies
Chen, Q., Ke, H., Dai, Z., & Liu, Z. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.09.018 · Cited by 209 · see citing works
Wu, L., Zou, Y., Deng, C., Cheng, R., Meng, F., & Zhong, Z. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.035 · Cited by 187 · see citing works
Self-citationPagels, R. F., & Prud’homme, R. K. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.09.001 · Cited by 182 · see citing works
Design of nanocarriers based on complex biological barriers in vivo for tumor therapy
Liu, J., Li, M., Luo, Z. Y., Dai, L., Guo, X., & Cai, K. (2017) · Nano Today · doi:10.1016/j.nantod.2017.06.010 · Cited by 157 · see citing works
Combination antitumor therapy with targeted dual-nanomedicines
Dai, W., Wang, X., Song, G., Liu, T., He, B., Zhang, H., Wang, X., & Zhang, Q. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.03.001 · Cited by 139 · see citing works
Self-citationZhang, C., An, T., Wang, D., Wan, G., Zhang, M., Wang, H., Zhang, S., Li, R., Yang, X., & Wang, Y. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.02.030 · Cited by 133 · see citing works
Biodegradable polymers for targeted delivery of anti-cancer drugs
Doppalapudi, S., Jain, A., Domb, A. J., & Khan, W. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1156671 · Cited by 125 · see citing works
Liu, L., Cao, F., Liu, X., Wang, H., Zhang, C., Sun, H., Wang, C., Leng, X., Song, C. X., Kong, D., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b01135 · Cited by 117 · see citing works
Zou, Y., Meng, F., Deng, C., & Zhong, Z. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.08.022 · Cited by 112 · see citing works
Self-citationEngineering red‐blood‐cell‐membrane–coated nanoparticles for broad biomedical applications
Gao, W., & Zhang, L. (2015) · AIChE Journal · doi:10.1002/aic.14735 · Cited by 105 · see citing works
Li, Z., Qiu, L., Chen, Q., Hao, T., Qiao, M., Zhao, H., Zhang, J., Hu, H., Zhao, X., Chen, D., et al. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.09.014 · Cited by 103 · see citing works
Zhang, P., Zhang, H., He, W., Zhao, D., Song, A., & Luan, Y. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.5b01758 · Cited by 103 · see citing works
Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying
Wan, F., & Yang, M. (2015) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2015.12.025 · Cited by 102 · see citing works
Hybrid PLGA-Organosilica Nanoparticles with Redox-Sensitive Molecular Gates
Quesada, M., Muniesa, C., & Botella, P. (2013) · Chemistry of Materials · doi:10.1021/cm400700g · Cited by 91 · see citing works
Fang, Y., Yang, W., Cheng, L., Meng, F., Zhang, J., & Zhong, Z. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.10.013 · Cited by 79 · see citing works
Self-citationWu, B., Yu, P., Cui, C., et al. (2015) · Biomaterials Science · doi:10.1039/c4bm00462k · Cited by 64 · see citing works
Chen, L., Chen, T., Fang, W., et al. (2013) · Biomacromolecules · doi:10.1021/bm401215w · Cited by 63 · see citing works
Xia, J., Du, Y., Huang, L., Chaurasiya, B., Tu, J., Webster, T. J., & Sun, C. (2018) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2017.12.017 · Cited by 63 · see citing works
Yang, W., Zou, Y., Meng, F., et al. (2016) · Advanced Materials · doi:10.1002/adma.201600065 · Cited by 62 · see citing works
Wu, J., Zhang, J., Deng, C., Meng, F., Cheng, R., & Zhong, Z. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b15105 · Cited by 57 · see citing works
Self-citationZhang, Y., Wu, K., Sun, H., Zhang, J., Yuan, J., & Zhong, Z. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b17718 · Cited by 54 · see citing works
Self-citationKhoee, S., & Rahmatolahzadeh, R. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.02.027 · Cited by 48 · see citing works
Sun, B., Deng, C., Meng, F., Zhang, J., & Zhong, Z. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.08.048 · Cited by 48 · see citing works
Self-citationYang, W., Xia, Y., Zou, Y., Meng, F., Zhang, J., & Zhong, Z. (2017) · Chemistry of Materials · doi:10.1021/acs.chemmater.7b02953 · Cited by 45 · see citing works
Self-citationWu, J., Zhang, J., Deng, C., et al. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b00380 · Cited by 33 · see citing works
Multimodality Imaging of Coiled‐Coil Mediated Self‐Assembly in a “Drug‐Free” Therapeutic System
Zhang, R., Yang, J., Chu, T.-W., et al. (2015) · Advanced Healthcare Materials · doi:10.1002/adhm.201400679 · Cited by 30 · see citing works
Isolated lung model for assessing drug absorption from PLGA microparticles
Park, K. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.03.003 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
- Authors
- Wang, X., Cheng, R., Cheng, L., & Zhong, Z.
- Affiliations
- Soochow University (CN)
- Corresponding author
- Cheng, Ru
- Zhong, Zhiyuan
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-03-19
- Volume
- 19
- Issue
- 4
- Pages
- 1368-1373
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- OpenAlex
- W2789619448
- Cited by
- 28
- References
- 48
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 4
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomacromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (51373113, 51633005)
- Priority Academic Program Development of Jiangsu Higher Education Institution
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- alpha-lipoic acid, smart nanoparticles, glutathione-responsive release, doxorubicin, controlled drug delivery, anticancer drug delivery, B16F10 melanoma cells, biodegradable polymers, nanoparticle stability, pharmacokinetics, tumor targeting
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Antioxidants, Dioxanes, Doxorubicin, Flow Cytometry, Glutathione, Humans, Thioctic Acid, Neoplasms, Drug Delivery Systems, Nanoparticles, Biodegradable Plastics, Drug Liberation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review