Biodegradable Micelles Based on Poly(ethylene glycol)-b-polylipopeptide Copolymer: A Robust and Versatile Nanoplatform for Anticancer Drug Delivery
Abstract
Poly(ethylene glycol)- b -polypeptide block copolymer micelles, with excellent safety, are one of the most clinically studied nanocarriers for anticancer drug delivery. Notably, self-assembled nanosystems based on hydrophobic polypeptides showing typically a low drug loading and burst drug release are limited to preclinical studies. Here, we report that poly(ethylene glycol)- b -poly(α-aminopalmitic acid) (PEG- b -PAPA) block copolymer could be easily prepared with tailored M n through ring-opening polymerization of α-aminopalmitic acid N -carboxyanhydride (APA-NCA). Interestingly, PEG- b -PAPA copolymers exhibited superb solubility in common organic solvents (including CHCl 3, CH 2 Cl 2, and THF), while stable nanomicelles were formed in phosphate buffer, with a small size of 59 nm and a low critical micelle concentration of 2.38 mg/L. These polylipopeptide micelles (Lipep-Ms) allowed facile loading of a potent anticancer drug, docetaxel (DTX), likely due to the existence of a strong interaction between the lipophilic drug and polylipopeptide in the core. Notably, cRGD-peptide-functionalized Lipep-Ms (cRGD-Lipep-Ms) were also obtained with similar biophysical characteristics. The in vitro studies showed efficient cellular uptake of DTX-loaded cRGD-Lipep-Ms by B16F10 cells and fast intracellular drug release due to the enzymatic degradation of PAPA blocks in endo/lysosome, leading to a pronounced anticancer effect (IC 50 = 0.15 μg DTX equiv/mL). The in vivo therapy studies showed that DTX–cRGD-Lipep-Ms exhibited superior tumor growth inhibition of B16F10 melanoma, improved survival rate, and little side effects as compared to free DTX. These polylipopeptide micelles appear as a promising and robust nanoplatform for anticancer drug delivery.
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Drugs entrapped in micelles are protected from unexpected interactions and biodegradation in the in vivo environment, resulting in prolongation of half-life and improved efficiency.
“Moreover, drugs entrapped in micelles are protected from unexpected interactions and biodegradation in vivo environment, resulting in prolongation of the half-life and improved efficiency [49,50,51].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [50]
Cites
Cancer nanomedicine: progress, challenges and opportunities
Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.108 · Cited by 5,873 · see citing works
Doxil® — The first FDA-approved nano-drug: Lessons learned
Barenholz, Y. (. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.03.020 · Cited by 4,792 · see citing works
Functional Supramolecular Polymers
Aida, T., Meijer, E. W., & Stupp, S. I. (2012) · Science · doi:10.1126/science.1205962 · Cited by 3,703 · see citing works
Self-Assembly and Mineralization of Peptide-Amphiphile Nanofibers
Hartgerink, J. D., Beniash, E., & Stupp, S. I. (2001) · Science · doi:10.1126/science.1063187 · Cited by 3,607 · see citing works
Nanomedicine in cancer therapy: Challenges, opportunities, and clinical applications
WICKI, A. N., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.030 · Cited by 1,962 · see citing works
Solid lipid nanoparticles for parenteral drug delivery
Wissing, S. A., Kayser, O., & Müller, R. H. (2004) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2003.12.002 · Cited by 1,494 · see citing works
Self-Assembled Lipid−Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform
Zhang, L., Chan, J. M., Gu, F., Rhee, J., Wang, A. Z., Radovic‐Moreno, A. F., Alexis, F., Langer, R., & Farokhzad, O. C. (2008) · ACS Nano · doi:10.1021/nn800275r · Cited by 1,042 · see citing works
Progress of drug-loaded polymeric micelles into clinical studies
Cabral, H., & Kataoka, K. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.06.042 · Cited by 837 · see citing works
Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come
Yingchoncharoen, P., Kalinowski, D. S., & Richardson, D. R. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.012070 · Cited by 744 · see citing works
Investigating the optimal size of anticancer nanomedicine
Tang, L., Yang, X., Yin, Q., Cai, K., Wang, H., Chaudhury, I., Yao, C., Zhou, Q., Kwon, M., Hartman, J. A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411499111 · Cited by 658 · see citing works
Miura, Y., Takenaka, T., Toh, K., Wu, S., Nishihara, H., Kano, M. R., Ino, Y., Nomoto, T., Matsumoto, Y., Koyama, H., et al. (2013) · ACS Nano · doi:10.1021/nn402662d · Cited by 462 · see citing works
cRGD‐Functionalized Polymer Micelles for Targeted Doxorubicin Delivery
Nasongkla, N., Shuai, X., Ai, H., Weinberg, B. D., Pink, J. J., Boothman, D. A., & Gao, J. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200460800 · Cited by 434 · see citing works
Synthesis of Side-Chain Modified Polypeptides
Deming, T. J. (2015) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00292 · Cited by 420 · see citing works
Deng, C., Wu, J., Cheng, R., et al. (2013) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2013.10.008 · Cited by 371 · see citing works
Self-citationThe binding conformation of Taxol in β-tubulin: A model based on electron crystallographic density
Snyder, J. P., Nettles, J. H., Cornett, B., Downing, K. H., & Nogales, E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051309398 · Cited by 362 · see citing works
Accelerating the Translation of Nanomaterials in Biomedicine
Mitragotri, S., Anderson, D. G., Chen, X. S., Chow, E. K., Ho, D., Kabanov, A. V., Karp, J. M., Kataoka, K., Mirkin, C. A., Petrosko, S. H., et al. (2015) · ACS Nano · doi:10.1021/acsnano.5b03569 · Cited by 350 · see citing works
Superior Penetration and Retention Behavior of 50 nm Gold Nanoparticles in Tumors
Huo, S., Ma, H., Huang, K., Liu, J., Wei, T., Jin, S., Zhang, J., He, S., & Liang, X. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2071 · Cited by 342 · see citing works
Self-citationStimuli responsive synthetic polypeptides derived from N-carboxyanhydride (NCA) polymerisation
Huang, J., & Heise, A. (2013) · Chemical Society Reviews · doi:10.1039/c3cs60063g · Cited by 336 · see citing works
αVβ3 Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug
Graf, N., Bielenberg, D. R., Kolishetti, N., Muus, C., Banyard, J., Farokhzad, O. C., & Lippard, S. J. (2012) · ACS Nano · doi:10.1021/nn301148e · Cited by 327 · see citing works
Improvement of drug safety by the use of lipid-based nanocarriers
Lim, S. B., Banerjee, A., & Önyüksel, H. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.06.002 · Cited by 325 · see citing works
Lu, H., Wang, J., Song, Z., et al. (2013) · Chemical Communications · doi:10.1039/c3cc46317f · Cited by 301 · see citing works
Polysaccharide‐block‐polypeptide Copolymer Vesicles: Towards Synthetic Viral Capsids
Schatz, C., Louguet, S., Meins, J. L., et al. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200805895 · Cited by 288 · see citing works
Zhu, D., Tao, W., Zhang, H., Liu, G., Wang, T., Zhang, L., Zeng, X., & Mei, L. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.11.031 · Cited by 279 · see citing works
Puhr, M., Hoefer, J., Schäfer, G., Erb, H. H. H., Oh, S. J., Klocker, H., Heidegger, I. M., Neuwirt, H., & Čulig, Z. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.08.011 · Cited by 263 · see citing works
Antitumor Activity of Peptide Amphiphile Nanofiber-Encapsulated Camptothecin
Soukasene, S., Toft, D. J., Moyer, T. J., et al. (2011) · ACS Nano · doi:10.1021/nn203343z · Cited by 251 · see citing works
Kato, K., Chin, K., Yoshikawa, T., Yamaguchi, K., Tsuji, Y., Esaki, T., Sakai, K., Kimura, M., Hamaguchi, T., Shimada, Y., et al. (2012) · Investigational New Drugs · doi:10.1007/s10637-011-9709-2 · Cited by 237 · see citing works
Lyseng-Williamson, K. A., & Fenton, C. (2005) · Drugs · doi:10.2165/00003495-200565170-00007 · Cited by 226 · see citing works
Nomoto, T., Fukushima, S., Kumagai, M., Takeda, K. M., Arnida, Matsumoto, Y., Oba, M., Miyata, K., Osada, K., Nishiyama, N., et al. (2014) · Nature Communications · doi:10.1038/ncomms4545 · Cited by 198 · see citing works
A critical review of lipid-based nanoparticles for taxane delivery
Feng, L., & Mumper, R. J. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.07.006 · Cited by 191 · see citing works
Lipid-coated polymeric nanoparticles for cancer drug delivery
Krishnamurthy, S., Vaiyapuri, R., Zhang, L., & Chan, J. M. (2015) · Biomaterials Science · doi:10.1039/c4bm00427b · Cited by 182 · see citing works
Development of polymeric micelles for targeting intractable cancers
Nishiyama, N., Matsumura, Y., & Kataoka, K. (2016) · Cancer Science · doi:10.1111/cas.12960 · Cited by 181 · see citing works
Clinical application of polymeric micelles for the treatment of cancer
Varela-Moreira, A., Shi, Y., Fens, M. H. A. M., Lammers, T., Hennink, W. E., & Schiffelers, R. M. (2017) · Materials Chemistry Frontiers · doi:10.1039/c6qm00289g · Cited by 168 · see citing works
Preparation of Multifunctional and Multireactive Polypeptides via Methionine Alkylation
Kramer, J. R., & Deming, T. J. (2012) · Biomacromolecules · doi:10.1021/bm300807b · Cited by 166 · see citing works
Mochida, Y., Cabral, H., Miura, Y., Albertini, F., Fukushima, S., Osada, K., Nishiyama, N., & Kataoka, K. (2014) · ACS Nano · doi:10.1021/nn500498t · Cited by 163 · see citing works
Xu, H., Yao, Q., Cai, C., Gou, J., Zhang, Y. X., Zhong, H., & Tang, X. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.012 · Cited by 158 · see citing works
Zhu, Y., Zhang, J., Meng, F., Deng, C., Cheng, R., Feijén, J., & Zhong, Z. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.014 · Cited by 134 · see citing works
Self-citationThe antitumor effect of novel docetaxel-loaded thermosensitive micelles
Li, R., Yang, M., Li, R., Ding, Y., Qian, X., Yu, L., & Jiang, X. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.01.015 · Cited by 126 · see citing works
Chemically tunable mucin chimeras assembled on living cells
Kramer, J. R., Onoa, B., Bustamante, C., & Bertozzi, C. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516127112 · Cited by 121 · see citing works
Lipid prodrug nanocarriers in cancer therapy
Mura, S., Bui, D. T., Couvreur, P., & Nicolas, J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.01.021 · Cited by 114 · see citing works
Multifunctionality of lipid-core micelles for drug delivery and tumour targeting
Sawant, R. R., & Torchilin, V. P. (2010) · Molecular Membrane Biology · doi:10.3109/09687688.2010.516276 · Cited by 109 · see citing works
He, C., Cai, P., Li, J., Zhang, T., Lin, L. Q., Abbasi, A. Z., Henderson, J. T., Rauth, A. M., & Wu, X. Y. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.12.019 · Cited by 103 · see citing works
Zou, Y., Fang, Y., Meng, H., Meng, F., Deng, C., Zhang, J., & Zhong, Z. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.05.060 · Cited by 95 · see citing works
Self-citationZhong, Y., Wang, C., Cheng, R., Cheng, L., Meng, F., Liu, Z., & Zhong, Z. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.07.054 · Cited by 90 · see citing works
Self-citationJain, S., Gollapalli, S., Agrawal, A. K., Kushwah, V., & Thanki, K. (2015) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00281 · Cited by 85 · see citing works
Advances in lipid-based drug delivery: enhancing efficiency for hydrophobic drugs
Wang, G., Wang, J., Wu, W., To, S. S. T., Zhao, H., & Wang, J. (2015) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2015.1021681 · Cited by 78 · see citing works
Drug release of pH-sensitive poly( l -aspartate)-b-poly(ethylene glycol) micelles with POSS cores
Pu, Y., Zhang, L., Zheng, H., He, B., & Gu, Z. (2013) · Polymer Chemistry · doi:10.1039/c3py00965c · Cited by 66 · see citing works
Chen, P., Qiu, M., Deng, C., Meng, F., Zhang, J., Cheng, R., & Zhong, Z. (2015) · Biomacromolecules · doi:10.1021/acs.biomac.5b00113 · Cited by 65 · see citing works
Self-citationPolymeric micelles for targeted tumor therapy of platinum anticancer drugs
Mochida, Y., Cabral, H., & Kataoka, K. (2017) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2017.1307338 · Cited by 64 · see citing works
Zhou, J., Chen, P., Deng, C., et al. (2013) · Macromolecules · doi:10.1021/ma4014669 · Cited by 60 · see citing works
Self-citationChirality-mediated polypeptide micelles for regulated drug delivery
Ding, J., Li, C., Zhang, Y., Xu, W., Wang, J., & Chen, X. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.09.043 · Cited by 59 · see citing works
Moyle, P. M., Dai, W. H., Zhang, Y., et al. (2014) · Bioconjugate Chemistry · doi:10.1021/bc500108b · Cited by 58 · 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-citationSun, 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-citationInhibiting Solid Tumor Growth In Vivo by Non‐Tumor‐Penetrating Nanomedicine
Lv, S., Tang, Z., Song, W., Zhang, D., Li, M., Liu, H., Cheng, J., Zhong, W., & Chen, X. (2017) · Small · doi:10.1002/smll.201600954 · Cited by 47 · see citing works
Poly(aspartic acid)-based Degradable Assemblies for Highly Efficient Gene Delivery
Nie, J., Dou, X.-B., Hu, H., Yu, B., Chen, D., Wang, R., & Xu, F. (2014) · ACS Applied Materials & Interfaces · doi:10.1021/am506730t · Cited by 45 · see citing works
A Scalable Synthesis of l -Leucine-N-carboxyanhydride
Smeets, N. M. B., van der Weide, P. L. J., Meuldijk, J., Vekemans, J. A. J. M., & Hulshof, L. A. (2005) · Organic Process Research & Development · doi:10.1021/op058009e · Cited by 44 · see citing works
Cao, W., Zeng, X., Liu, G., et al. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.08.016 · Cited by 33 · see citing works
Lu, C. T., Li, X., Xia, W., Lu, S., Luo, H., Ye, D., Zhang, Y., & Liu, D. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.038 · Cited by 32 · see citing works
Comer, A. M., & Goa, K. L. (2000) · Drugs & Aging · doi:10.2165/00002512-200017010-00004 · Cited by 25 · see citing works
Facilitated Synthesis of Heterofunctional Glycopolypeptides
Krannig, K.-S., Doriti, A., & Schlaad, H. (2014) · Macromolecules · doi:10.1021/ma500379m · Cited by 24 · see citing works
Francini, N., Purdie, L., Alexander, C., et al. (2015) · Macromolecules · doi:10.1021/acs.macromol.5b00447 · Cited by 21 · see citing works
Lipophilic nalmefene prodrugs to achieve a one-month sustained release
Gaekens, T., Guillaume, M., Borghys, H., de Zwart, L. L., de Vries, R., Embrechts, R. C. A., Vermeulen, A., Megens, A. A. H. P., Leysen, J. E., Herdewijn, P. A., et al. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.04.029 · Cited by 14 · see citing works
Xiang, Y., Yang, Y., Guo, G.-L., et al. (2015) · Clinical and Experimental Medicine · doi:10.1007/s10238-015-0371-4 · Cited by 5 · see citing works
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Recent Advances in Nanomicelles Delivery Systems.
Tawfik, S. M., Azizov, S., Elmasry, M. R., Sharipov, M., & Lee, Y.-I. (2020) · Nanomaterials · doi:10.3390/nano11010070 · Cited by 156 · see citing works
- Authors
- Qiu, M., Ouyang, J., Sun, H., Meng, F., Cheng, R., Zhang, J., Cheng, L., Lan, Q., Deng, C., & Zhong, Z.
- Affiliations
- Soochow University (CN)
- Second Affiliated Hospital of Soochow University (CN)
- Corresponding author
- Deng, Chao
- Zhong, Zhiyuan
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-08-11
- Volume
- 9
- Issue
- 33
- Pages
- 27587-27595
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2743792273
- Cited by
- 45
- References
- 63
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 10 · 2019: 6 · 2018: 11
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (51473110, 51633005)
- 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 Biology › RNA Interference and Gene Delivery
- Keywords
- ring-opening polymerization, docetaxel, cRGD peptide, targeted drug delivery, melanoma, B16F10 melanoma cells, enzymatic degradation, intracellular drug release, tumor growth inhibition, biodegradable nanocarriers
- MeSH terms
- Antineoplastic Agents, Drug Carriers, Lipoproteins, Micelles, Polyethylene Glycols, Drug Delivery Systems
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