Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems
Abstract
Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well-characterized polymeric drug carriers that have been broadly implemented in the delivery of anticancer therapeutics. In an attempt to improve the tumor accumulation of HPMA copolymer-based drug delivery systems, their in vivo application was combined with radiotherapy and hyperthermia. As the effects of radiotherapy and hyperthermia were considered to depend significantly on the tumor model used, we first analyzed the accumulation of two differently sized HPMA copolymers in three different types of tumors, based on the syngeneic Dunning rat prostate carcinoma model. Subsequently, in these three models, the effects of different doses of radiotherapy and hyperthermia on the tumor accumulation of 31 kDa poly(HPMA), 65 kDa poly(HPMA) and 28 kDa poly(HPMA)-GFLG-doxorubicin were evaluated. It was found that the polymeric drug delivery systems accumulated effectively in all three tumor models. In addition, as opposed to hyperthermia, radiotherapy was found to improve the concentrations of the copolymers independent of the tumor model used. Based on these findings, we conclude that radiotherapy is an effective means for increasing the tumor accumulation of (polymeric) drug delivery systems, and we propose that the combination of carrier-based chemotherapy with radiotherapy holds significant potential for improving the treatment of advanced solid malignancies.
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Auxiliary means such as topical hyperthermia, radiotherapy and high intensity focused ultrasound can be used to enhance EPR effect.
“Some auxiliary means, such as topical hyperthermia, radiotherapy and high intensity focused ultrasound, etc., can also be used to enhance this effect [158–160].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [159]
Cites
Matsumura, Y., & Maeda, H. (1986) · PubMed · Cited by 6,771 · see citing works
Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review
Maeda, H., Wu, J., Sawa, T., Matsumura, Y., & Hori, K. (2000) · Journal of Controlled Release · doi:10.1016/s0168-3659(99)00248-5 · Cited by 6,565 · see citing works
The dawning era of polymer therapeutics
Duncan, R. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1088 · Cited by 3,273 · see citing works
Dvorak, H. F., Brown, L. F., Detmar, M. J., & Dvořàk, A. M. (1995) · Europe PMC (PubMed Central) · Cited by 3,103 · see citing works
Hyperthermia in combined treatment of cancer
Wust, P., Hildebrandt, B., Sreenivasa, G., Rau, B., Gellermann, J., Riess, H. B., FELIX, R., & Schlag, P. (2002) · The Lancet Oncology · doi:10.1016/s1470-2045(02)00818-5 · Cited by 2,002 · see citing works
Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis
Garcı́a-Barros, M., Paris, F., Cordon‐Cardo, C., Lyden, D. C., Rafii, S., Haimovitz‐Friedman, A., FUKS, Z. Y., & Kolesnick, R. (2003) · Science · doi:10.1126/science.1082504 · Cited by 1,591 · see citing works
Salacinski, P., McLean, C., Sykes, J. E., Clement‐Jones, V., & Lowry, P. J. (1981) · Analytical Biochemistry · doi:10.1016/0003-2697(81)90703-x · Cited by 1,129 · see citing works
Vasey, P. A., Kaye, S. B., Morrison, R. A., Twelves, C. J., Wilson, P., Duncan, R., Thomson, A. H., Murray, L. S., Hilditch, T. E., Murray, T., et al. (1999) · PubMed · Cited by 689 · see citing works
Hyperthermia enables tumor-specific nanoparticle delivery: effect of particle size.
Kong, G., Braun, R. D., & Dewhirst, M. W. (2000) · PubMed · Cited by 630 · see citing works
HPMA copolymer–anticancer drug conjugates: design, activity, and mechanism of action
Kopeček, J. (2000) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(00)00075-8 · Cited by 561 · see citing works
Drug Delivery and Transport to Solid Tumors
Jang, S. H., Wientjes, M. G., Lü, D., & Au, J. L. ‐. (2003) · Pharmaceutical Research · doi:10.1023/a:1025785505977 · Cited by 491 · see citing works
Noguchi, Y., Wu, J., Duncan, R., Strohalm, J., Ulbrich, K., Akaike, T., & Maeda, H. (1998) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1998.tb00563.x · Cited by 470 · see citing works
Self-citationCharacterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature.
Kong, G., Braun, R. D., & Dewhirst, M. W. (2001) · PubMed · Cited by 438 · see citing works
Hepatic Drug Targeting: Phase I Evaluation of Polymer-Bound Doxorubicin
Seymour, L. W., Ferry, D. R., Anderson, D., Hesslewood, S., Julyan, P. J., Poyner, R., Doran, J., Young, A., Burtles, S. S., & Kerr, D. J. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.20.6.1668 · Cited by 435 · see citing works
Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470
Satchi‐Fainaro, R., Puder, M., Davies, J. W., Tran, H. T., Sampson, D. A., Greene, A. K., Corfas, G., & Folkman, J. (2004) · Nature Medicine · doi:10.1038/nm1002 · Cited by 345 · see citing works
Seymour, L. W., Miyamoto, Y., Maeda, H., Brereton, M., Strohalm, J., Ulbrich, K., & Duncan, R. (1995) · European Journal of Cancer · doi:10.1016/0959-8049(94)00514-6 · Cited by 337 · see citing works
Self-citationDifferential response of normal and tumor microcirculation to hyperthermia.
Dudar, T. E., & Jain, R. K. (1984) · PubMed · Cited by 307 · see citing works
Netti, P. A., Baxter, L. T., Boucher, Y., Skalak, R., & Jain, R. K. (1995) · PubMed · Cited by 265 · see citing works
Water soluble polymers in tumor targeted delivery
Kopec̆ek, J., Kopečková, P., Minko, T., Lu, Z., & Peterson, C. M. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00330-3 · Cited by 227 · see citing works
Rademaker-Lakhai, J. M., Terret, C., Howell, S. B., Baud, C., de Boer, R. F., Pluim, D., Beijnen, J. H., Schellens, J. H. M., & Droz, J. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0315 · Cited by 214 · see citing works
Enhancement of fluid filtration across tumor vessels: Implication for delivery of macromolecules
Netti, P. A., Hamberg, L. M., Babich, J. W., Kierstead, D., Graham, W. A., Hunter, G. J. S., Wolf, G. L., Fischman, A. J., Boucher, Y., & Jain, R. K. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3137 · Cited by 203 · see citing works
Gianasi, E., Wasil, M., Evagorou, E. G., Keddle, A., Wilson, G. D., & Duncan, R. (1999) · European Journal of Cancer · doi:10.1016/s0959-8049(99)00030-1 · Cited by 186 · see citing works
Samaniego, F., Markham, P. D., Gendelman, R., Watanabe, Y., Kao, V., Kowalski, K., SONNABEND, J. A., Pintus, A., Gallo, R. C., & Ensoli, B. (1998) · PubMed Central · Cited by 182 · see citing works
Feng, D., Nagy, J. A., Pyne, K., Hammel, I., Dvorak, H. F., & Dvořàk, A. M. (1999) · Microcirculation · doi:10.1111/j.1549-8719.1999.tb00085.x · Cited by 175 · see citing works
Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin
Satchi‐Fainaro, R., Mamluk, R., Wang, X., Short, S. M., Nagy, J. A., Feng, D., Dvořàk, A. M., Dvorak, H. F., Puder, M., Mukhopadhyay, D., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.02.007 · Cited by 173 · see citing works
Targeted Delivery of Doxorubicin by HPMA Copolymer-Hyaluronan Bioconjugates
Luo, Y., Bernshaw, N. J., Lu, Z., Kopec̆ek, J., & Prestwich, G. D. (2002) · Pharmaceutical Research · doi:10.1023/a:1015170907274 · Cited by 172 · see citing works
Determinants of drug delivery and transport to solid tumors
Au, J. L., Jang, S., Zheng, J., Chen, C.-T., Song, S., Hu, L., & Wientjes, M. G. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00308-x · Cited by 165 · see citing works
Davies, C. D. L., Lundstrøm, L. M., Frengen, J., Eikenes, L., Bruland, Ø. S., Kaalhus, O., Hjelstuen, M. H. B., & Brekken, C. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0576 · Cited by 163 · see citing works
Radiation-induced apoptosis in microvascular endothelial cells
Langley, R. E., Bump, E. A., Quartuccio, S., Medeiros, D., & Braunhut, S. J. (1997) · British Journal of Cancer · doi:10.1038/bjc.1997.119 · Cited by 153 · see citing works
Rissanen, T. T., Markkanen, J. E., Arve, K., Rutanen, J., Kettunen, M. I., Vajanto, I., Jauhiainen, S., Cashion, L. M., Gruchała, M., Närvänen, O., et al. (2002) · The FASEB Journal · doi:10.1096/fj.02-0377fje · Cited by 149 · see citing works
Targeting tumor angiogenic vasculature using polymer–RGD conjugates
Mitra, A., Mulholland, J., Nan, A., McNeill, E., Ghandehari, H., & Line, B. R. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.09.023 · Cited by 148 · see citing works
Shiah, J.-G., Dvořák, M., Kopečková, P., Sun, Y., Peterson, C. M., & Kopec̆ek, J. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(00)00374-9 · Cited by 140 · see citing works
Park, J. S., Qiao, L., Su, Z.-Z., Hinman, D., Willoughby, K. A., McKinstry, R. P., Yacoub, A., Duigou, G. J., Young, C. S. H., Grant, S., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204258 · Cited by 139 · see citing works
Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels
Hallahan, D. E., Geng, L., Qu, S., Scarfone, C., Giorgio, T. D., Donnelly, E. F., Gao, X., & Clanton, J. A. (2003) · Cancer Cell · doi:10.1016/s1535-6108(02)00238-6 · Cited by 134 · see citing works
Effect of radiation on interstitial fluid pressure and oxygenation in a human tumor xenograft.
Znati, C. A., Rosenstein, M., Boucher, Y., Epperly, M. W., Bloomer, W. D., & Jain, R. K. (1996) · PubMed · Cited by 131 · see citing works
Lammers, T., Kühnlein, R., Kissel, M., Šubr, V., Etrych, T., Pola, R., Pechar, M., Ulbrich, K., Storm, G., Huber, P. E., et al. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.09.010 · Cited by 131 · see citing works
Self-citationAntibody-targeted Polymer–doxorubicin Conjugates with pH-controlled Activation
Ulbrich, K., Etrych, T., Chytil, P., Jelínková, M., & Řı́hová, B. (2004) · Journal of drug targeting · doi:10.1080/10611860400011869 · Cited by 128 · see citing works
Self-citationDuncan, R., Kopec̆ek, J., Rejmanová, P., & Lloyd, J. B. (1983) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(83)90258-1 · Cited by 127 · see citing works
David, A., Kopečková, P., Minko, T., Rubinstein, A., & Kopec̆ek, J. (2003) · European Journal of Cancer · doi:10.1016/j.ejca.2003.07.001 · Cited by 110 · see citing works
Feng, D., Nagy, J. A., Pyne, K., Hammel, I., Dvorak, H. F., & Dvořàk, A. M. (1999) · Microcirculation · doi:10.1080/713773925 · Cited by 107 · see citing works
Shiah, J.-G., Sun, Y., Kopečková, P., Peterson, C. M., Straight, R. C., & Kopec̆ek, J. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00325-x · Cited by 105 · see citing works
Li, C., Shi, K., Wu, Q., Tansey, W., Hunter, N. R., Buchmiller, L., Milas, L., Charnsangavej, C., & Wallace, S. (2000) · PubMed · Cited by 102 · see citing works
Synthesis of Starlike N-(2-Hydroxypropyl)methacrylamide Copolymers: Potential Drug Carriers
Wang, D., Kopečková, P., Minko, T., Nanayakkara, V., & Kopec̆ek, J. (2000) · Biomacromolecules · doi:10.1021/bm0000236 · Cited by 100 · see citing works
Chung, Y., Jian, J. J., Cheng, S. H., Tsai, S. Y., Chuang, V. P., Soong, T. C., Lin, Y., & Horng, C. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2721 · Cited by 97 · see citing works
Toschi, E., Barillari, G., Sgadari, C., Bacigalupo, I., Cereseto, A., Carlei, D., Palladino, C., Zietz, C., Leone, P., Stürzl, M., et al. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.10.2934 · Cited by 90 · see citing works
Cope, D. A., Dewhirst, M. W., Friedman, H. S., Bigner, D. D., & Zalutsky, M. R. (1990) · PubMed · Cited by 78 · see citing works
Kovář, M., Strohalm, J., Etrych, T., Ulbrich, K., & Řı́hová, B. (2002) · Bioconjugate Chemistry · doi:10.1021/bc010063m · Cited by 70 · see citing works
Self-citationClinical Implications of N-(2-Hydroxypropyl)Methacrylamide Copolymers
Rihova, B., & Kubáčková, K. (2003) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201033489711 · Cited by 69 · see citing works
Lee, Y. J., Galoforo, S., Berns, C. M., Erdös, G., Gupta, A., Ways, D. K., & Corry, P. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.48.28790 · Cited by 60 · see citing works
Nishiyama, N., Nori, A., Malugin, A., Kasuya, Y., Kopečková, P., & Kopec̆ek, J. (2003) · PubMed · Cited by 49 · see citing works
Synthesis and characterization of HPMA copolymer–aminopropylgeldanamycin conjugates
Kasuya, Y., Lu, Z., Kopečková, P., Minko, T., Tabibi, S. E., & Kopec̆ek, J. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00318-2 · Cited by 48 · see citing works
Hauck, M., Dewhirst, M. W., Bigner, D. D., & Zalutsky, M. R. (1997) · PubMed · Cited by 47 · see citing works
Tang, A., Kopečková, P., & Kopec̆ek, J. (2003) · Pharmaceutical Research · doi:10.1023/a:1022639701388 · Cited by 45 · see citing works
Synthetic Polymers Conjugated to Monoclonal Antibodies: Vehicles for Tumour-Targeted Drug Delivery
Seymour, L. W., FLANAGAN, P. A., Al‐Shamkhani, A., Šubr, V., Ulbrich, K., Cassidy, J., & Duncan, R. (1991) · Selective Cancer Therapeutics · doi:10.1089/sct.1991.7.59 · Cited by 42 · see citing works
Self-citationSchuster, J. M., Zalutsky, M. R., Noska, M. A., Dodge, R. K., Friedman, H. S., Bigner, D. D., & Dewhirst, M. W. (1995) · International Journal of Hyperthermia · doi:10.3109/02656739509004948 · Cited by 41 · see citing works
Effect of hyperthermia on microvascular permeability to macromolecules in normal and tumor tissues.
Le, G., & Jain, R. (1985) · PubMed · Cited by 39 · see citing works
Lubaroff, D. M., Canfield, L., Feldbush, T. L., & Bonney, W. W. (1977) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/58.6.1677 · Cited by 35 · see citing works
Řı́hová, B., Jelínková, M., Strohalm, J., Šťastný, M., Hovorka, O., Plocová, D., Kovář, M., Dráberová, L., & Ulbrich, K. (2000) · Bioconjugate Chemistry · doi:10.1021/bc9901696 · Cited by 32 · see citing works
Self-citationTechnology evaluation: PK1, Pfizer/Cancer Research UK.
Bilim, V. N. (2003) · PubMed · Cited by 30 · see citing works
Ding, H., Prodinger, W. M., & Kopec̆ek, J. (2006) · Bioconjugate Chemistry · doi:10.1021/bc0503162 · Cited by 30 · see citing works
Hauck, M., & Zalutsky, M. R. (2004) · International Journal of Hyperthermia · doi:10.1080/02656730410001695906 · Cited by 22 · see citing works
Wróblewski, S., Berenson, M. M., Kopečková, P., & Kopec̆ek, J. (2001) · Journal of Controlled Release · doi:10.1016/s0168-3659(01)00338-8 · Cited by 22 · see citing works
Peschke, P., Klein, V. A., Wolber, G., Friedrich, E., & Hahn, E. W. (1999) · PubMed · doi:10.14670/hh-14.461 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
4 of the 67 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy
Pérez‐Herrero, E., & Fernández‐Medarde, A. (2015) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2015.03.018 · Cited by 1,888 · see citing works
Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress
Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.09.063 · Cited by 1,324 · see citing works
Self-citationDanhier, F. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.11.015 · Cited by 1,288 · see citing works
Tumor targeting via EPR: Strategies to enhance patient responses
Golombek, S. K., May, J.-N., Theek, B., Appold, L., Drude, N., Kiessling, F., & Lammers, T. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.07.007 · Cited by 1,262 · see citing works
Self-citationNanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer?
Nakamura, Y., Mochida, A., Choyke, P. L., & Kobayashi, H. (2016) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00437 · Cited by 1,107 · see citing works
Kobayashi, H., Watanabe, R., & Choyke, P. L. (2014) · Theranostics · doi:10.7150/thno.7193 · Cited by 996 · see citing works
Nanomedicine in cancer therapy
Fan, D., Cao, Y., Cao, M., Wang, Y., Cao, Y., & Gong, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01536-y · Cited by 944 · see citing works
Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements
Her, S., Jaffray, D. A., & Allen, C. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.12.012 · Cited by 865 · see citing works
Greco, F., & Vicent, M. J. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.05.006 · Cited by 654 · see citing works
Recent Advances in Tumor Targeting via EPR Effect for Cancer Treatment
Subhan, M. A., Yalamarty, S. S. K., Filipczak, N., Parveen, F., & Torchilin, V. P. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11060571 · Cited by 623 · see citing works
Noninvasive Imaging of Nanomedicines and Nanotheranostics: Principles, Progress, and Prospects
Kunjachan, S., Ehling, J., Storm, G., Kiessling, F. M., & Lammers, T. (2015) · Chemical Reviews · doi:10.1021/cr500314d · Cited by 480 · see citing works
Self-citationThe tumor EPR effect for cancer drug delivery: Current status, limitations, and alternatives
Sun, R., Xiang, J., Zhou, Q., Piao, Y., Tang, J., Shao, S., Zhou, Z., Bae, Y. H., & Shen, Y. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114614 · Cited by 442 · see citing works
Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
Nanotheranostics and image-guided drug delivery: current concepts and future directions
Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100228v · Cited by 397 · see citing works
Self-citationOverchuk, M., & Zheng, G. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.024 · Cited by 383 · see citing works
Strategies to improve the EPR effect: A mechanistic perspective and clinical translation
Ikeda-Imafuku, M., Wang, L. L.-W., Rodrigues, D., Shaha, S., Zhao, Z., & Mitragotri, S. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.043 · Cited by 330 · see citing works
Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research
Egusquiaguirre, S. P., Igartúa, M., Hernández, R. M., & Pedraz, J. L. (2012) · Clinical & Translational Oncology · doi:10.1007/s12094-012-0766-6 · Cited by 267 · see citing works
Synergistic nanomedicine by combined gene and photothermal therapy
Kim, J., Kim, J., Jeong, C., & Kim, W. J. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.12.018 · Cited by 262 · see citing works
Zhang, Y., Li, N., Suh, H., & Irvine, D. J. (2017) · Nature Communications · doi:10.1038/s41467-017-02251-3 · Cited by 248 · see citing works
Lammers, T., Šubr, V., Ulbrich, K., Peschke, P., Huber, P. E., Hennink, W. E., & Storm, G. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.02.040 · Cited by 240 · see citing works
Self-citationGold nanoparticles in combinatorial cancer therapy strategies
Beik, J., Khateri, M., Khosravi, Z., Kamrava, S. K., Kooranifar, S., Ghaznavi, H., & Shakeri‐Zadeh, A. (2019) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2019.02.025 · Cited by 230 · see citing works
Enhancement of EPR Effect for Passive Tumor Targeting: Current Status and Future Perspectives
Vagena, I.-A., Malapani, C., Gatou, Μ.-A., Lаgopati, N., & Pavlatou, E. A. (2025) · Applied Sciences · doi:10.3390/app15063189 · Cited by 232 · see citing works
Gao, G., Jiang, Y., Sun, W., Guo, Y., Jia, H., Yu, X., Pan, G., & Wu, F. (2019) · Small · doi:10.1002/smll.201900501 · Cited by 221 · see citing works
Current Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines
Durymanov, M. O., Rosenkranz, A. A., & Sobolev, A. S. (2015) · Theranostics · doi:10.7150/thno.11742 · Cited by 190 · see citing works
Huang, D., Sun, L., Huang, L., & Chen, Y. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020124 · Cited by 176 · see citing works
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Radiation effects on the tumor microenvironment: Implications for nanomedicine delivery
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Polymeric nanomedicines for image-guided drug delivery and tumor-targeted combination therapy
Lammers, T., Šubr, V., Ulbrich, K., Hennink, W. E., Storm, G., & Kiessling, F. M. (2010) · Nano Today · doi:10.1016/j.nantod.2010.05.001 · Cited by 136 · see citing works
Self-citationImage-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy
Lammers, T., Šubr, V., Peschke, P., Kühnlein, R., Hennink, W. E., Ulbrich, K., Kiessling, F. M., Heilmann, M., Debus, J., Huber, P. E., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604561 · Cited by 130 · see citing works
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Lammers, T. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.11.028 · Cited by 124 · see citing works
Self-citationNoninvasive Optical Imaging of Nanomedicine Biodistribution
Kunjachan, S., Gremse, F., Theek, B., Koczera, P., Pola, R., Pechar, M., Etrych, T., Ulbrich, K., Storm, G., Kiessling, F. M., et al. (2012) · ACS Nano · doi:10.1021/nn303955n · Cited by 112 · see citing works
Self-citationZhu, Y., Jia, H., Gao, G., Pan, G., Jiang, Y., Li, P., Zhou, N., Li, C., She, C., Ulrich, N. W., et al. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119668 · Cited by 107 · see citing works
Nanomedicine in Cancer Therapeutics: Current Perspectives from Bench to Bedside
Abdullah, K. M., Sharma, G., Singh, A. P., & Siddiqui, J. A. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02368-w · Cited by 117 · see citing works
Breakthrough discoveries in drug delivery technologies: The next 30 years
Brambilla, D., Luciani, P., & Leroux, J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.056 · Cited by 104 · see citing works
Dhaliwal, A. K., & Zheng, G. (2019) · Theranostics · doi:10.7150/thno.37204 · Cited by 103 · see citing works
Overcoming tumor microenvironment obstacles: Current approaches for boosting nanodrug delivery
Wang, X., Zhang, H., Chen, X., Wu, C., Ding, K., Sun, G., Luo, Y., & Xiang, D. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.05.043 · Cited by 104 · see citing works
Conjugates of doxorubicin with graft HPMA copolymers for passive tumor targeting
Etrych, T., Chytil, P., Mrkvan, T., Šírová, M., Řı́hová, B., & Ulbrich, K. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.04.017 · Cited by 98 · see citing works
Self-citationEkdawi, S. N., Stewart, J., Dunne, M., Stapleton, S., Mitsakakis, N., Dou, Y. N., Jaffray, D. A., & Allen, C. J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.04.006 · Cited by 93 · see citing works
Datta, N. R., Krishnan, S., Speiser, D. E., Neufeld, E., Kuster, N., Bodis, S., & Hofmann, H. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.09.016 · Cited by 92 · see citing works
Liu, J. F., Lan, Z., Ferrari, C., Stein, J. M., Higbee-Dempsey, E. M., Yan, L., Amirshaghaghi, A., Cheng, Z., Issadore, D., & Tsourkas, A. (2019) · ACS Nano · doi:10.1021/acsnano.9b05660 · Cited by 90 · see citing works
Polymer–Drug Conjugates for Novel Molecular Targets
Sanchis, J., Canal, F., Lucas-Domínguez, R., & Vicent, M. J. (2010) · Nanomedicine · doi:10.2217/nnm.10.71 · Cited by 89 · see citing works
Zhou, Z., Li, L., Yang, Y., Xu, X., & Huang, Y. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.04.059 · Cited by 86 · see citing works
Organic nanocarriers for cancer drug delivery
López-Dávila, V., Seifalian, A. M., & Loizidou, M. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.02.011 · Cited by 83 · see citing works
Auffinger, B., Morshed, R. A., Tobias, A. L., Cheng, Y., Ahmed, A. U., & Lesniak, M. S. (2013) · Oncotarget · doi:10.18632/oncotarget.937 · Cited by 83 · see citing works
Cancer Drug Delivery: Considerations in the Rational Design of Nanosized Bioconjugates
Kobayashi, H., Türkbey, B., Watanabe, R., & Choyke, P. L. (2014) · Bioconjugate Chemistry · doi:10.1021/bc500481x · Cited by 82 · see citing works
Melancon, M. P., Elliott, A. M., Shetty, A. M., Huang, Q., Stafford, R. J., & Li, C. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.06.030 · Cited by 82 · see citing works
Nanomedicine and tumor heterogeneity: Concept and complex reality
Ekdawi, S. N., Jaffray, D. A., & Allen, C. J. (2016) · Nano Today · doi:10.1016/j.nantod.2016.06.006 · Cited by 82 · see citing works
Stapleton, S., Dunne, M., Milosevic, M., Tran, C. W., Gold, M. J., Vedadi, A., McKee, T. D., Ohashi, P. S., Allen, C. J., & Jaffray, D. A. (2018) · ACS Nano · doi:10.1021/acsnano.7b06301 · Cited by 80 · see citing works
Imaging-assisted anticancer nanotherapy
Dasgupta, A., Biancacci, I., Kiessling, F., & Lammers, T. (2020) · Theranostics · doi:10.7150/thno.38288 · Cited by 74 · see citing works
Self-citationPlasmonic photothermal therapy increases the tumor mass penetration of HPMA copolymers
Gormley, A. J., Larson, N., Banisadr, A., Robinson, R., Frazier, N., Ray, A., & Ghandehari, H. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.12.007 · Cited by 71 · see citing works
Biological rationale for the design of polymeric anti-cancer nanomedicines
Zhou, Y., & Kopec̆ek, J. (2012) · Journal of drug targeting · doi:10.3109/1061186x.2012.723213 · Cited by 67 · see citing works
Yang, Y., Zhou, Z., He, S., Fan, T., Jin, Y., Zhu, X. D., Chen, C., Zhang, Z., & Huang, Y. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.12.007 · Cited by 65 · see citing works
Molecular imaging of HPMA copolymers: Visualizing drug delivery in cell, mouse and man☆
Lu, Z. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.12.007 · Cited by 63 · see citing works
Overcoming cellular multidrug resistance using classical nanomedicine formulations
Kunjachan, S., Błauż, A., Möckel, D., Theek, B., Kiessling, F. M., Etrych, T., Ulbrich, K., van Bloois, L., Storm, G., Bartosz, G., et al. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.08.028 · Cited by 62 · see citing works
Self-citationNanotechnology in Radiation Oncology
Wang, A. Z., & Tepper, J. E. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.0699 · Cited by 61 · see citing works
Larnaudie, S. C., Sanchis, J., Nguyen, T., Peltier, R., Catrouillet, S., Brendel, J. C., Porter, C. J. H., Jolliffe, K. A., & Perrier, S. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.047 · Cited by 60 · see citing works
Radiolabelled Polymeric Materials for Imaging and Treatment of Cancer: Quo Vadis?
Pant, K., Sedláček, O., Nadar, R. A., Hrubý, M., & Stephan, H. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201601115 · Cited by 56 · see citing works
Swetha, K. L., & Roy, A. (2018) · Drug Delivery and Translational Research · doi:10.1007/s13346-018-0578-5 · Cited by 51 · see citing works
Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment
Egorova, V. S., Kolesova, E. P., Lopus, M., Yan, N., Parodi, A., & Zamyatnin, A. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071848 · Cited by 49 · see citing works
Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor Stroma
Martínez-Zubiaurre, I., Chalmers, A. J., & Hellevik, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01679 · Cited by 52 · see citing works
Integrating nanomedicine into clinical radiotherapy regimens
DuRoss, A. N., Neufeld, M. J., Rana, S. R., Thomas, C. R., & Sun, C. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.07.002 · Cited by 49 · see citing works
Mimicking Tumors: Toward More Predictive In Vitro Models for Peptide- and Protein-Conjugated Drugs
van den Brand, D., Massuger, L. F. A. G., Brock, R. E., & Verdurmen, W. P. R. (2017) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6b00699 · Cited by 48 · see citing works
Jiang, Y., Lu, H., Dağ, A., Hart‐Smith, G., & Stenzel, M. H. (2016) · Journal of Materials Chemistry B · doi:10.1039/c5tb02576a · Cited by 42 · see citing works
Gray, B. P., McGuire, M. J., & Brown, K. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072938 · Cited by 39 · see citing works
Rajora, A. K., Ahire, E. D., Rajora, M. A. K., Singh, S., Bhattacharya, J., & Zhang, H. (2024) · Smart Medicine · doi:10.1002/smmd.20230035 · Cited by 38 · see citing works
Gouardères, S., Mingotaud, A., Vicendo, P., & Gibot, L. (2020) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2020.1814735 · Cited by 34 · see citing works
Advances in nuclei targeted delivery of nanoparticles for the management of cancer
Goyal, P., & Malviya, R. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188881 · Cited by 33 · see citing works
Delivery of Nanoconstructs in Cancer Therapy: Challenges and Therapeutic Opportunities
Saw, W. S., Anasamy, T., Foo, Y. Y., Kwa, Y. C., Kue, C. S., Yeong, C. H., Kiew, L. V., Lee, H. B., & Chung, L. Y. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000206 · Cited by 33 · see citing works
Improving chemoradiotherapy with nanoparticle therapeutics.
Eblan, M. J., & Wang, A. Z. (2013) · PubMed · doi:10.3978/j.issn.2218-676x.2013.08.04 · Cited by 31 · see citing works
Rama, E., May, J., Rix, A., Lammers, T., & Kiessling, F. M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152346 · Cited by 28 · see citing works
Self-citationImage-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment
Appelbe, O. K., Zhang, Q., Pelizzari, C. A., Weichselbaum, R. R., & Kron, S. J. (2016) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.6b00465 · Cited by 27 · see citing works
Tehrani, M. H. H., Kashkooli, F. M., & Soltani, M. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.108050 · Cited by 24 · see citing works
Polycation-based nanoparticles for RNAi-mediated cancer treatment
Ballarín-González, B., Ebbesen, M. F., & Howard, K. A. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.09.023 · Cited by 23 · see citing works
pH-triggered delivery of magnetic nanoparticles depends on tumor volume
Pershina, A. G., Brikunova, O. Y., Demin, A. M., Shevelev, O. B., Разумов, И. А., Zavjalov, E. L., Malkeyeva, D., Владимировна, К. Е., Krakhmal, N. V., Vtorushin, S. V., et al. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102086 · Cited by 23 · see citing works
Lammers, T., Šubr, V., Ulbrich, K., Peschke, P., Huber, P. E., Hennink, W. E., Storm, G., & Kiessling, F. M. (2010) · Nanomedicine · doi:10.2217/nnm.10.130 · Cited by 20 · see citing works
Self-citationEtrych, T., Kovář, L., Šubr, V., Braunová, A., Pechar, M., Chytil, P., Řı́hová, B., & Ulbrich, K. (2010) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911509353485 · Cited by 20 · see citing works
Self-citationRasel, M. S. I., Mohona, F. A., Akter, W., Kabir, S., Chowdhury, A. A., Chowdhury, J. A., Hassan, M. A., Mamun, A. A., Ghose, D. K., Ahmad, Z., et al. (2022) · Journal of Oncology · doi:10.1155/2022/9396760 · Cited by 20 · see citing works
Nanoparticles for Stem Cell Therapy Bioengineering in Glioma
Ruiz-Garcia, H. J., Alvarado-Estrada, K., Krishnan, S., Quiñones‐Hinojosa, A., & Trifiletti, D. M. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.558375 · Cited by 19 · see citing works
Singh, M., Ma, R., & Zhu, L. K. (2021) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-020-02308-4 · Cited by 18 · see citing works
Warnders, F.-J., Hooge, M. N. L., de Vries, E. G. E., & Kosterink, J. G. W. (2018) · Medicinal Research Reviews · doi:10.1002/med.21498 · Cited by 18 · see citing works
Papaioannou, L., & Avgoustakis, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114075 · Cited by 16 · see citing works
He, S., Zhou, Z., Li, L., Yang, Q., Yang, Y., Guan, S., Zhang, J., Zhu, X., Jin, Y., & Huang, Y. (2014) · Drug Delivery · doi:10.3109/10717544.2014.911991 · Cited by 16 · see citing works
Emerging strategies based on nanomaterials for ionizing radiation-optimized drug treatment of cancer
Yi, X., Shen, M., Liu, X., & Gu, J. (2021) · Nanoscale · doi:10.1039/d1nr03034e · Cited by 15 · see citing works
Radiation-assisted strategies provide new perspectives to improve the nanoparticle delivery to tumor
Zhang, D., He, J., & Zhou, M. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114642 · Cited by 15 · see citing works
Combined external beam radiotherapy with carbon ions and tumor targeting endoradiotherapy
Melzig, C., Golestaneh, A. F., Mier, W., Schwager, C., Das, S., Schlegel, J., Lasitschka, F., Kauczor, H., Debus, J., Haberkorn, U., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.25695 · Cited by 14 · see citing works
Self-citationNanomedicine formulations for combination therapies
Lammers, T., Storm, G., & Kiessling, F. M. (2010) · Nano Reviews · doi:10.3402/nano.v1i0.5705 · Cited by 14 · see citing works
Self-citationMacromolecular nanotheranostics for multimodal anticancer therapy
Veld, R. H. I. '., Storm, G., Hennink, W. E., Kiessling, F. M., & Lammers, T. (2011) · Nanoscale · doi:10.1039/c1nr10733j · Cited by 13 · see citing works
Self-citationMašek, V., Anzenbacherová, E., Etrych, T., Strohalm, J., Ulbrich, K., & Anzenbacher, P. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.037986 · Cited by 12 · see citing works
Self-citationHeating Induced Nanoparticle Migration and Enhanced Delivery in Tumor Treatment Using Nanotechnology
Gu, Q., & Zhu, L. K. (2024) · Bioengineering · doi:10.3390/bioengineering11090900 · Cited by 11 · see citing works
Multifunctional Polymeric Nanosystems for Tumor-Targeted Delivery
Magadala, P., van Vlerken, L. E., Shahiwala, A., & Amiji, M. M. (2008) · Fundamental biomedical technologies · doi:10.1007/978-0-387-76554-9_2 · Cited by 10 · see citing works
Drug–polymer conjugates: Challenges, opportunities, and future prospects in clinical trials
Bajwa, N., Mahal, S., Singh, P. A., Jyoti, K., Dewangan, P., Madan, J., & Baldi, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-91663-9.00011-4 · Cited by 9 · see citing works
Gu, Q., Dockery, L. T., Daniel, M., Bieberich, C. J., Ma, R., & Zhu, L. K. (2021) · Fluids · doi:10.3390/fluids6080272 · Cited by 8 · see citing works
Nanoparticles targeting tumor-associated macrophages: A novel anti-tumor therapy
Chen, S., Qin, F., Wang, M., Wei, Y., Qian, Z., & Wei, X. (2021) · Nano Research · doi:10.1007/s12274-021-3781-5 · Cited by 8 · see citing works
Price, L., Rivera, J. N., Madden, A. J., Herity, L. B., Piscitelli, J. A., Mageau, S., Santos, C., Roques, J., Midkiff, B. R., Feinberg, N. N., et al. (2021) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359211053700 · Cited by 8 · see citing works
Pressure Gradients in Solid Tumors
Stapleton, S., & Milosevic, M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7876-8_9 · Cited by 8 · see citing works
Lim, H., Martínez‐Santiesteban, F., Jensen, M. D., Chen, A., Wong, E., & Scholl, T. J. (2020) · Tomography · doi:10.18383/j.tom.2020.00024 · Cited by 7 · see citing works
- Authors
- Lammers, T., Peschke, P., Kühnlein, R., Subr, V., Ulbrich, K., Debus, J., Huber, P., Hennink, W., & Storm, G.
- Affiliations
- German Cancer Research Center (DE)
- Czech Academy of Sciences, Institute of Macromolecular Chemistry (CZ)
- Heidelberg University (DE)
- Utrecht University (NL)
- Corresponding author
- Lammers, Twan
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 117
- Issue
- 3
- Pages
- 333-341
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2054393872
- Cited by
- 124
- References
- 67
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 8 · 2012: 7
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- HPMA copolymer, polymeric drug carriers, radiotherapy, hyperthermia, tumor accumulation, polymeric drug delivery, doxorubicin, combination therapy, solid tumors
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Antineoplastic Agents, Combined Modality Therapy, Doxorubicin, Drug Carriers, Hyperthermia, Induced, Immunohistochemistry, Iodine Radioisotopes, Male, Methacrylates, Neoplasms, Prostatic Neoplasms, Radiotherapy, Tissue Distribution, Drug Delivery Systems, Rats
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