The accelerated blood clearance (ABC) phenomenon: Clinical challenge and approaches to manage
Abstract
Despite the clinical introduction of an increasing number of polyethylene glycol (PEG)-conjugated substances, PEG has been named as the cause of an unexpected immunogenic response known as the "accelerated blood clearance (ABC) phenomenon." This phenomenon has been extensively observed during the repeated administration of PEG-conjugated substances and PEGylated nanocarriers including PEGylated liposomes, PEGylated nanoparticles, PEGylated micelles, etc., resulting in the increased clearance and reduced efficacy of PEG-conjugated substances/PEGylated nanocarriers. In this review, therefore, we focused on the possible mechanisms underlying the induction of such a phenomenon and emphasized the factors affecting its magnitude. In addition, the clinical implications of the ABC phenomenon on the therapeutic efficacy of PEG-conjugated substances/PEGylated nanocarriers, along with the new approaches that can be applied to manage and/or abrogate the induction of the ABC phenomenon, are also discussed.
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?
In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance.
“In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [217]
In preclinical studies, the presence of anti-PEG IgM in animal serum caused a complete loss of the efficacy of mRNA therapeutics.
“In preclinical studies, the presence of anti-PEG IgM in animal serum accelerated nanoparticle clearance and caused a complete loss of the efficacy of mRNA therapeutics217,218.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [217]
PEG-lipids could induce hypersensitivity reactions by stimulating the complement system.
“Lipid components may activate host immune responses following systemic or local administration; for example, PEG-lipids could induce hypersensitivity reactions by stimulating the complement system127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]
Numerous natural and synthetic polymers have been investigated as alternatives to PEG, several of which are under evaluation in clinical trials.
“To ameliorate safety concerns, numerous natural and synthetic polymers have been investigated as alternatives to PEG, of which several are under evaluation in clinical trials127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]
Anti-PEG antibodies could result in fast systemic clearance of subsequently administered PEGylated nanoparticles by accelerated blood clearance.
“Moreover, anti-PEG antibodies could result in fast systemic clearance of subsequently administered PEGylated nanoparticles by accelerated blood clearance127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]
Lipid components may activate host immune responses following systemic or local administration.
“Lipid components may activate host immune responses following systemic or local administration; for example, PEG-lipids could induce hypersensitivity reactions by stimulating the complement system127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]
The accelerated blood clearance phenomenon may change the bioavailability and biodistribution of the drug encapsulated in PEGylated nanoparticles and cause side effects.
“The accelerated blood clearance phenomenon may change the bioavailability and biodistribution of the drug encapsulated in PEGylated nanoparticles and, thus, cause side effects127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [169]
Cites
Matsumura, Y., & Maeda, H. (1986) · PubMed · Cited by 6,771 · see citing works
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · see citing works
Drug Delivery Systems: Entering the Mainstream
Allen, T. M., & Cullis, P. R. (2004) · Science · doi:10.1126/science.1095833 · Cited by 4,552 · see citing works
Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes
Klibanov, A. L., Maruyama, K., Torchilin, V. P., & Huang, L. (1990) · FEBS Letters · doi:10.1016/0014-5793(90)81016-h · Cited by 2,030 · see citing works
Abuchowski, A., Es, T. V., Palczuk, N. C., & Davis, F. F. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40291-2 · Cited by 1,358 · see citing works
Abuchowski, A., McCoy, J. R., Palczuk, N. C., Es, T. V., & Davis, F. F. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40292-4 · Cited by 1,276 · see citing works
Martin, F., Oliver, A. M., & Kearney, J. F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00129-7 · Cited by 987 · see citing works
Armstrong, J. K., Hempel, G., Koling, S., Chan, L. S., Fisher, T., Meiselman, H. J., & Garratty, G. (2007) · Cancer · doi:10.1002/cncr.22739 · Cited by 699 · see citing works
Dams, E. T. M., Laverman, P., Oyen, W. J. G., Storm, G., Scherphof, G. L., van der Meer, J. W. M., Corstens, F. H. M., & Boerman, O. C. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35391-1 · Cited by 606 · see citing works
Ishida, T., Ichihara, M., Wang, X., Yamamoto, K., Kimura, J., Majima, E., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.01.005 · Cited by 558 · see citing works
Self-citationLasiç, D. D., Martin, F. J., Gabizón, A., Huang, S. K., & Papahadjopoulos, D. (1991) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(91)90162-2 · Cited by 545 · see citing works
Senior, J. H., Delgado, C., Fisher, D., Tilcock, C., & Gregoriadis, G. (1991) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(91)90337-8 · Cited by 521 · see citing works
Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes
Ishida, T., & Kiwada, H. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.11.005 · Cited by 496 · see citing works
Self-citationThe Proteolytic Activation Systems of Complement
Reid, K. B. M., & Porter, R. (1981) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.50.070181.002245 · Cited by 480 · see citing works
Chanan-Khan, A., Szebeni, J., Savay, S., Liebes, L., Rafique, N. M., Alving, C. R., & Muggia, F. M. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg374 · Cited by 479 · see citing works
Vos, Q., Lees, A., Wu, Z.-Q., Snapper, C. M., & Mond, J. J. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.00607.x · Cited by 469 · see citing works
In Vivo Targeted Delivery of Nanoparticles for Theranosis
Koo, H., Huh, M. S., Sun, I., Yuk, S. H., Choi, K., Kim, K., & Kwon, I. C. (2011) · Accounts of Chemical Research · doi:10.1021/ar2000138 · Cited by 447 · see citing works
Wang, X., Ishida, T., & Kiwada, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.02.010 · Cited by 421 · see citing works
Self-citationAllen, C. J., Santos, N. D., Gallagher, R., Chiu, G. N. C., Shu, Y., Li, W. M., Johnstone, S. A., Janoff, A. S., Mayer, L. D., Webb, M. S., et al. (2002) · Bioscience Reports · doi:10.1023/a:1020186505848 · Cited by 388 · see citing works
PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner
Ishida, T., Wang, X., Shimizu, T., Nawata, K., & Kiwada, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.05.015 · Cited by 382 · see citing works
Self-citationIshida, T., Harada, M., Wang, X., Ichihara, M., Irimura, K., & Kiwada, H. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.04.003 · Cited by 365 · see citing works
Self-citationGanson, N. J., Kelly, S. J., Scarlett, E., Sundy, J. S., & Hershfield, M. S. (2005) · Arthritis Research & Therapy · doi:10.1186/ar1861 · Cited by 350 · see citing works
Accelerated clearance of PEGylated liposomes in rats after repeated injections
Ishida, T., Maeda, R., Ichihara, M., Irimura, K., & Kiwada, H. (2003) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00462-5 · Cited by 327 · see citing works
Self-citationLaverman, P., Carstens, M. G., Boerman, O. C., Dams, E. T. M., Oyen, W. J. G., van Rooijen, N., Corstens, F. H. M., & Storm, G. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29419-2 · Cited by 298 · see citing works
Ishida, T., Atobe, K., Wang, X., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.08.017 · Cited by 290 · see citing works
Self-citationSupramolecular Nanodevices: From Design Validation to Theranostic Nanomedicine
Cabral, H., Nishiyama, N., & Kataoka, K. (2011) · Accounts of Chemical Research · doi:10.1021/ar200094a · Cited by 290 · see citing works
Richter, A. W., & Akerblom, E. B. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000233309 · Cited by 282 · see citing works
Judge, A. D., McClintock, K., Phelps, J. R., & MacLachlan, I. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.09.014 · Cited by 280 · see citing works
Ishida, T., Ichihara, M., Wang, X., & Kiwada, H. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.08.001 · Cited by 270 · see citing works
Self-citationGabizón, A., Dagan, A., Goren, D., Barenholz, Y., & FUKS, Z. Y. (1982) · PubMed · Cited by 263 · see citing works
Non-viral and hybrid vectors in human gene therapy: an update
Schmidt‐Wolf, G., & Schmidt‐Wolf, I. G. H. (2003) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(03)00005-4 · Cited by 253 · see citing works
Polymer-coated long-circulating microparticulate pharmaceuticals
Torchilin, V. P. (1998) · Journal of Microencapsulation · doi:10.3109/02652049809006831 · Cited by 236 · see citing works
Zandvoort, A., & Timens, W. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01953.x · Cited by 225 · see citing works
Semple, S. C., Harasym, T. O., Clow, K. A., Ansell, S. M., Klimuk, S. K., & Hope, M. J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.078113 · Cited by 211 · see citing works
Ambegia, E., Ansell, S. M., Cullis, P. R., Heyes, J. A., Palmer, L., & MacLachlan, I. (2005) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2005.02.001 · Cited by 203 · see citing works
Recent advances in liposomal drug-delivery systems
Chonn, A., & Cullis, P. R. (1995) · Current Opinion in Biotechnology · doi:10.1016/0958-1669(95)80115-4 · Cited by 200 · see citing works
Accelerated Blood Clearance Phenomenon Upon Repeated Injection of PEG-modified PLA-nanoparticles
Ishihara, T., Takeda, M., Sakamoto, H., Kimoto, A., Kobayashi, C., Takasaki, N., Yuki, K., Tanaka, K., Takenaga, M., Igarashi, R., et al. (2009) · Pharmaceutical Research · doi:10.1007/s11095-009-9943-x · Cited by 196 · see citing works
Self-citationLü, W., Wan, J., She, Z., & Jiang, X. (2006) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.11.015 · Cited by 193 · see citing works
Szebeni, J., Baranyi, L., Sávay, S., Bodo, M., Morse, D. S., Bašta, M., Stahl, G. L., Bünger, R., & Alving, C. R. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.3.h1319 · Cited by 172 · see citing works
Webb, M. S., Saxon, D., Wong, F. M. P., Lim, H. J., Wang, Z., Bally, M. B., Choi, L. S. L., Cullis, P. R., & Mayer, L. D. (1998) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(98)00077-7 · Cited by 171 · see citing works
Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats
Ichihara, M., Shimizu, T., Imoto, A., Hashiguchi, Y., Uehara, Y., Ishida, T., & Kiwada, H. (2010) · Pharmaceutics · doi:10.3390/pharmaceutics3010001 · Cited by 157 · see citing works
Self-citationIshihara, T., Maeda, T., Sakamoto, H., Takasaki, N., Shigyo, M., Ishida, T., Kiwada, H., Mizushima, Y., & Mizushima, T. (2010) · Biomacromolecules · doi:10.1021/bm100754e · Cited by 155 · see citing works
Self-citationParticle size-dependent triggering of accelerated blood clearance phenomenon
Koide, H., Asai, T., Hatanaka, K., Urakami, T., Ishii, T., Kenjo, E., Nishihara, M., Yokoyama, M., Ishida, T., Kiwada, H., et al. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.06.004 · Cited by 148 · see citing works
Self-citationAccelerated Clearance of Polyethylene Glycol-Modified Proteins by Anti-Polyethylene Glycol IgM
Cheng, T., Wu, P.-Y., Wu, M., Chern, J., & Roffler, S. R. (1999) · Bioconjugate Chemistry · doi:10.1021/bc980143z · Cited by 147 · see citing works
Koide, H., Asai, T., Hatanaka, K., Akai, S., Ishii, T., Kenjo, E., Ishida, T., Kiwada, H., Tsukada, H., & Oku, N. (2010) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2010.03.022 · Cited by 143 · see citing works
Self-citationShiraishi, K., Hamano, M., Ma, H., Kawano, K., Maitani, Y., Aoshi, T., Ishii, K. J., & Yokoyama, M. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.11.016 · Cited by 141 · see citing works
Suzuki, T., Ichihara, M., Hyodo, K., Yamamoto, E., Ishida, T., Kiwada, H., Ishihara, H., & Kikuchi, H. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.07.049 · Cited by 127 · see citing works
Self-citationSaadati, R., Dadashzadeh, S., Abbasian, Z., & Soleimanjahi, H. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0934-y · Cited by 127 · see citing works
Ishida, T., Kashima, S., & Kiwada, H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.11.009 · Cited by 125 · see citing works
Self-citationXu, H., Wang, K. Q., Deng, Y. H., et al. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.02.049 · Cited by 118 · see citing works
Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients
La-Beck, N. M., Zamboni, B. A., Gabizón, A., Schmeeda, H., Amantea, M., Gehrig, P. A., & Zamboni, W. C. (2011) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-011-1664-2 · Cited by 118 · see citing works
Ishida, T., Ichikawa, T., Ichihara, M., et al. (2004) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.12.011 · Cited by 116 · see citing works
Self-citationXu, H., Deng, Y., Chen, D., HONG, W., Lu, Y., & Dong, X. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2008.05.009 · Cited by 109 · see citing works
Tagami, T., Uehara, Y., Moriyoshi, N., Ishida, T., & Kiwada, H. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.12.013 · Cited by 93 · see citing works
Self-citationYagi, N., Manabe, I., Tottori, T., Ishihara, A., Ogata, F., Kim, J. H., Nishimura, S., Fujiu, K., Oishi, Y., Itaka, K., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3945 · Cited by 92 · see citing works
Hussain, S., Plückthun, A., Allen, T. M., & Zangemeister‐Wittke, U. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-07-0615 · Cited by 89 · see citing works
Romberg, B., Oussoren, C., Snel, C. J., Carstens, M. G., Hennink, W. E., & Storm, G. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.12.005 · Cited by 87 · see citing works
Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma
Miyazaki, T., Kato, H., Shitara, Y., Yoshikawa, M., Tajima, K., Masuda, N., Shouji, H., Tsukada, K., Nakajima, T., & Kuwano, H. (2000) · Cancer · doi:10.1002/1097-0142(20000901)89:5 · Cited by 84 · see citing works
Formann, E., Jessner, W., Bennett, L. N., et al. (2003) · Journal of Viral Hepatitis · doi:10.1046/j.1365-2893.2003.00446.x · Cited by 81 · see citing works
Effect of siRNA in PEG-coated siRNA-lipoplex on anti-PEG IgM production
Tagami, T., Nakamura, K., Shimizu, T., Ishida, T., & Kiwada, H. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.04.006 · Cited by 81 · see citing works
Self-citationDeng, Y., Zhao, Wang, Yan, Y., Ma, Zang, & She (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s30943 · Cited by 79 · see citing works
Chen, D., Shen, Y., Liu, Mu, M., Liang, L., Wang, & Sun (2011) · International Journal of Nanomedicine · doi:10.2147/ijn.s24344 · Cited by 78 · see citing works
Induction of CD4 + T-Cell-Independent Immunoglobulin Responses by Inactivated Influenza Virus
Sha, Z., & Compans, R. W. (2000) · Journal of Virology · doi:10.1128/jvi.74.11.4999-5005.2000 · Cited by 78 · see citing works
CpG motifs in pDNA-sequences increase anti-PEG IgM production induced by PEG-coated pDNA-lipoplexes
Tagami, T., Nakamura, K., Shimizu, T., Yamazaki, N., Ishida, T., & Kiwada, H. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.10.017 · Cited by 77 · see citing works
Self-citationSolid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria
Joshi, M., Pathak, S., Sharma, S., & Patravale, V. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.06.012 · Cited by 71 · see citing works
Zhao, Y., Wang, C., Wang, L., Yang, Q., Tang, W., She, Z., & Deng, Y. (2012) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.04.023 · Cited by 70 · see citing works
Cheng, T., Chen, B., Chern, J., Wu, M., & Roffler, S. R. (2000) · Bioconjugate Chemistry · doi:10.1021/bc990147j · Cited by 67 · see citing works
A Double-modulation Strategy in Cancer Treatment With a Chemotherapeutic Agent and siRNA
Nakamura, K., Lila, A. S. A., Matsunaga, M., Doi, Y., Ishida, T., & Kiwada, H. (2011) · Molecular Therapy · doi:10.1038/mt.2011.174 · Cited by 66 · see citing works
Self-citationKumagai, M., Kano, M. R., Morishita, Y., Ota, M., Imai, Y., Nishiyama, N., Sekino, M., Ueno, S., Miyazono, K., & Kataoka, K. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.06.002 · Cited by 64 · see citing works
Liu, Y., Reidler, H., Pan, J., Milunic, D., Qin, D., Chen, D., Vallejo, R. P., & Yin, R. (2011) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2011.07.003 · Cited by 64 · see citing works
The complement system in liposome clearance: Can complement deposition be inhibited?
Devine, D. V., & Bradley, A. J. (1998) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(97)00129-4 · Cited by 59 · see citing works
Li, C., Cao, J., Wang, Y., Zhao, X., Deng, C., Wei, N., Yang, J., & Cui, J. (2012) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23254 · Cited by 57 · see citing works
Ma, Y., Yang, Q., Wang, L., Zhou, X., Zhao, Y., & Deng, Y. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.11.014 · Cited by 57 · see citing works
Kanamycin A‐Derived Cationic Lipids as Vectors for Gene Transfection
Sainlos, M., Hauchecorne, M., Oudrhiri, N., et al. (2005) · ChemBioChem · doi:10.1002/cbic.200400344 · Cited by 57 · see citing works
Deng, Y., Yang, P., Ma, Zhao, She, Wang, Li, X., & Wang (2013) · International Journal of Nanomedicine · doi:10.2147/ijn.s41701 · Cited by 54 · see citing works
Pharmacokinetic change of nanoparticulate formulation “Lactosome” on multiple administrations
Hara, E., Makino, A., Kurihara, K., Yamamoto, F., Ozeki, E., & Kimura, S. (2012) · International Immunopharmacology · doi:10.1016/j.intimp.2012.07.011 · Cited by 54 · see citing works
Tc-99m-PEG-Liposomes for the Evaluation of Colitis in Crohn's Disease
Brouwers, A. H., Jong, D. D., Dams, E. T. M., et al. (2000) · Journal of drug targeting · doi:10.3109/10611860008997901 · Cited by 54 · see citing works
Taguchi, K., Urata, Y., Anraku, M., Watanabe, H., Kadowaki, D., Sakai, H., Horinouchi, H., Kobayashi, K., Tsuchida, E., Maruyama, T., et al. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.028852 · Cited by 51 · see citing works
Ma, H., Shiraishi, K., Minowa, T., Kawano, K., Yokoyama, M., Hattori, Y., & Maitani, Y. (2009) · Pharmaceutical Research · doi:10.1007/s11095-009-0018-9 · Cited by 51 · see citing works
Sun, W., Zou, W., Huang, G., et al. (2008) · Journal of drug targeting · doi:10.1080/10611860801927598 · Cited by 44 · see citing works
Li, C., Zhao, X., Wang, Y., et al. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.01.012 · Cited by 44 · see citing works
Lila, A. S. A., Eldin, N. E., Ichihara, M., Ishida, T., & Kiwada, H. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.08.030 · Cited by 39 · see citing works
Self-citationNagao, A., Lila, A. S. A., Ishida, T., & Kiwada, H. (2012) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2012.11.015 · Cited by 39 · see citing works
Self-citationCui, J., Li, C., Wang, C., Li, Y., Zhang, L., Zhang, L., & Yang, H. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.60.12.0011 · Cited by 39 · see citing works
Ishida, T., Maeda, R., Ichihara, M., et al. (2002) · PubMed · Cited by 36 · see citing works
Self-citationCui, J., Li, C., Wang, C., et al. (2008) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp/60.12.0011 · Cited by 32 · see citing works
Repeat Injection Studies of Technetium-99M-Labeled Peg-Liposomes in the Same Animal
Coins, B., Phillips, W. T., & Klipper, R. W. (1998) · Journal of Liposome Research · doi:10.3109/08982109809035531 · Cited by 31 · see citing works
Tardi, P. G., Swartz, E. N., Harasym, T. O., et al. (1997) · Journal of Immunological Methods · doi:10.1016/s0022-1759(97)00178-6 · Cited by 26 · see citing works
Oussoren, C., & Storm, G. (1999) · Journal of Liposome Research · doi:10.3109/08982109909018655 · Cited by 25 · see citing works
Taguchi, K., Ogaki, S., Watanabe, H., et al. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.177832 · Cited by 12 · see citing works
Cardiac pheochromocytoma: A new case reported
Knop, G., & Margaria, R. (2006) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2006.07.028 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · 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
mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555 · see citing works
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309 · see citing works
Targeting drugs to tumours using cell membrane-coated nanoparticles
Fang, R. H., Gao, W., & Zhang, L. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00699-x · Cited by 980 · see citing works
Fang, J., Islam, W., & Maeda, H. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.06.005 · Cited by 757 · see citing works
Hwang, D., Ramsey, J. D., & Kabanov, A. V. (2020) · Advanced drug delivery reviews · doi:10.1016/j.addr.2020.09.009 · Cited by 699 · see citing works
“Recently, the phenomenon of accelerated blood clearance (ABC) of PEG has gained a lot of attention due to its detrimental effects on the nanoparticle therapeutics which utilize PEG shielding [77].”
BackgroundKozma, G. T., Shimizu, T., Ishida, T., & Szebeni, J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.024 · Cited by 696 · see citing works
Self-citationHoang Thi, T. T., Pilkington, E. H., Nguyen, D. H., Lee, J. S., Park, K. D., & Truong, N. P. (2020) · Polymers · doi:10.3390/polym12020298 · Cited by 668 · see citing works
Anti‐ <scp>PEG</scp> immunity: emergence, characteristics, and unaddressed questions
Yang, Q., & Lai, S. K. (2015) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1339 · Cited by 593 · see citing works
Kim, J., Eygeris, Y., Gupta, M., & Sahay, G. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.014 · Cited by 514 · 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
The blood clearance kinetics and pathway of polymeric micelles in cancer drug delivery
Sun, X., Wang, G., Zhang, H., Hu, S., Liu, X., Tang, J., & Shen, Y. (2018) · ACS Nano · doi:10.1021/acsnano.8b02830 · Cited by 253 · see citing works
Kierstead, P. H., Okochi, H., Venditto, V. J., Chuong, T. C., Kivimae, S., Fréchet, J. M. J., & Szoka, F. C. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.06.023 · Cited by 210 · see citing works
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112 · see citing works
Leyva-Gómez, G., Cortés, H., Magaña, J. J., Leyva-García, N., Quintanar-Guerrero, D., & Florán, B. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.02.009 · Cited by 102 · see citing works
Gaspar, V. M., Gonçalves, C., de Melo-Diogo, D., Costa, E. C., Queiroz, J. A., Pichon, C., Sousa, F., & Correia, I. J. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.06.040 · Cited by 91 · see citing works
de Maar, J. S., Sofias, A. M., Porta Siegel, T., Vreeken, R. J., Moonen, C., Bos, C., & Deckers, R. (2020) · Theranostics · doi:10.7150/thno.38625 · Cited by 71 · see citing works
Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery
Wang, Y., van Steenbergen, M. J., Beztsinna, N., Shi, Y., Lammers, T., van Nostrum, C. F., & Hennink, W. E. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.09.013 · Cited by 66 · see citing works
Børresen, B., Hansen, A. E., Fliedner, F. P., Henriksen, J. R., Elema, D. R., Brandt-Larsen, M., Kristensen, L. K., Kristensen, A. T., Andresen, T. L., & Kjær, A. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s239172 · Cited by 28 · see citing works
- Authors
- Abu Lila, A. S., Kiwada, H., & Ishida, T.
- Affiliations
- Tokushima University (JP)
- Corresponding author
- Ishida, Tatsuhiro
- ORCID
- Ishida, Tatsuhiro
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 172
- Issue
- 1
- Pages
- 38-47
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W1987259801
- Cited by
- 721
- References
- 91
- Citations by year
- 2026: 80 · 2025: 73 · 2024: 70 · 2023: 80 · 2022: 76 · 2021: 55 · 2020: 62 · 2019: 46 · 2018: 50 · 2017: 27 · 2016: 38 · 2015: 34 · 2014: 26 · 2013: 3 · 2012: 1
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- 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
- accelerated blood clearance, PEGylation, polyethylene glycol, PEGylated liposomes, PEGylated nanoparticles, immunogenicity, drug clearance, treatment efficacy
- MeSH terms
- Animals, Complement Activation, Drug Carriers, Humans, Immunoglobulin M, Liposomes, Polyethylene Glycols, Spleen
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