Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts
Open accessAbstract
Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome.
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For fibrotic lesion, degradation of extracellular matrix using collagenase or hyaluronidase can be effective strategies to enhance accumulation.
“Besides, for the fibrotic lesion, degradation of the extracellular matrix using collagenase or hyaluronidase can be effective strategies to enhance accumulation [161, 162].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [162]
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Gabizón, A., Catane, R., Uziely, B., Kaufman, B., Safra, T., Cohen, R., Martin, F., Huang, A., & Barenholz, Y. (1994) · PubMed · Cited by 1,382 · see citing works
Yuan, F., Leunig, M., Huang, S. K., Berk, D. A., Papahadjopoulos, D., & Jain, R. K. (1994) · PubMed · Cited by 908 · see citing works
Dynamic imaging of collagen and its modulation in tumors in vivo using second-harmonic generation
Brown, E. B., McKee, T. D., DiTomaso, E., Pluen, A., Seed, B., Boucher, Y., & Jain, R. K. (2003) · Nature Medicine · doi:10.1038/nm879 · Cited by 836 · see citing works
(1990) · PubMed · Cited by 757 · see citing works
Jain, R. K., & Baxter, L. T. (1988) · PubMed · Cited by 710 · see citing works
Pluen, A., Boucher, Y., Ramanujan, S., McKee, T. D., Gohongi, T., di Tomaso, E., Brown, E. B., Izumi, Y., Campbell, R. B., Berk, D. A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081626898 · Cited by 604 · see citing works
Harris, L. N., Batist, G., Belt, R. J., Rovira, D. K., Navari, R. M., Azarnia, N., Welles, L., Winer, E. P., & TLC D‐99 Study Group (2001) · Cancer · doi:10.1002/cncr.10201 · Cited by 511 · see citing works
Boucher, Y., & Jain, R. K. (1992) · PubMed · Cited by 510 · see citing works
Polyethylenglykol-umhülltes (pegyliertes) liposomales Doxorubicin
Gabizón, A., & Martin, F. (1997) · Drugs · doi:10.2165/00003495-199700544-00005 · Cited by 478 · see citing works
Pulsatile pressures in the microcirculation of frog's mesentery
Wiederhielm, C. A., Woodbury, J. W., Kirk, S., & Rushmer, R. F. (1964) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1964.207.1.173 · Cited by 439 · see citing works
Permeation of the luminal capillary glycocalyx is determined by hyaluronan
Henry, C. B. S., & Duling, B. R. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.2.h508 · Cited by 426 · see citing works
Diffusion and convection in normal and neoplastic tissues.
Swabb, E. A., Wei, J., & Gullino, P. M. (1974) · PubMed · Cited by 398 · see citing works
Wu, N. Z., Da, D., Rudoll, T. L., Needham, D., Whorton, A. R., & Dewhirst, M. W. (1993) · PubMed · Cited by 365 · see citing works
Current Treatment of Osteosarcoma
Ferguson, W. S., & Goorin, A. M. (2001) · Cancer Investigation · doi:10.1081/cnv-100102557 · Cited by 295 · see citing works
Gabizón, A., & Martin, F. J. (1997) · Drugs · Cited by 292 · see citing works
Eikenes, L., Bruland, Ø. S., Brekken, C., & Davies, C. D. L. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1472 · Cited by 251 · see citing works
Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes
Symon, Z., PEYSER, A. B., Tzemach, D., Lyass, O., Sucher, E., Shezen, E., & Gabizón, A. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990701)86:1 · Cited by 214 · see citing works
Interstitial fluid pressure in rats measured with a modified wick technique
FADNES, H. O., Reed, R. K., & Aukland, K. (1977) · Microvascular Research · doi:10.1016/0026-2862(77)90138-8 · Cited by 189 · see citing works
Two-photon fluorescence correlation microscopy reveals the two-phase nature of transport in tumors
Alexandrakis, G., Brown, E. B., Tong, R. T., McKee, T. D., Campbell, R. B., Boucher, Y., & Jain, R. K. (2004) · Nature Medicine · doi:10.1038/nm981 · Cited by 178 · 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
Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy
van Haaren, P. M. A., VanBavel, E., Vink, H., & Spaan, J. A. E. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00117.2003 · Cited by 161 · see citing works
Adamson, R. H. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018197 · Cited by 148 · see citing works
Bruland, Ø. S., & Pihl, A. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00252-9 · Cited by 147 · see citing works
Role of a glycocalyx on coronary arteriole permeability to proteins: evidence from enzyme treatments
Huxley, V. H., & Williams, D. A. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.4.h1177 · Cited by 143 · see citing works
Davies, C. D. L., Berk, D. A., Pluen, A., & Jain, R. K. (2002) · British Journal of Cancer · doi:10.1038/sj.bjc.6600270 · Cited by 121 · see citing works
Fodstad, Ø., Brögger, A., Bruland, Ø. S., Solheim, Ø. P., Nesland, J. M., & Pihl, A. (1986) · International Journal of Cancer · doi:10.1002/ijc.2910380107 · Cited by 119 · see citing works
Vaage, J., Donovan, D., Uster, P. S., & Working, P. (1997) · British Journal of Cancer · doi:10.1038/bjc.1997.84 · Cited by 104 · see citing works
Hyaluronidase reduces human breast cancer xenografts in SCID mice
Shuster, S., Frost, G. I., Csoka, A. B., Formby, B., & Stern, R. (2002) · International Journal of Cancer · doi:10.1002/ijc.10668 · Cited by 95 · see citing works
Hyaluronidase enhances the activity of Adriamycin in breast cancer models in vitro and in vivo
Beckenlehner, K., Bannke, S., Spru�, T., Bernhardt, G., Sch�nenberger, H., & Schiess, W. (1992) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf01211802 · Cited by 81 · see citing works
Albanell, J., & Baselga, J. (2000) · PubMed · Cited by 68 · see citing works
Kohno, N., Ohnuma, T., & Truog, P. (1994) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf01236386 · Cited by 68 · see citing works
SMITH, K., Skelton, H. G., Turiansky, G. W., & WAGNER, K. (1997) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(97)70288-3 · Cited by 56 · see citing works
Brekken, C., Hjelstuen, M., Bruland, Ø. S., & Davies, C. D. L. (2000) · PubMed · Cited by 53 · see citing works
Brekken, C., Bruland, Ø. S., & Davies, C. D. L. (2001) · PubMed · Cited by 50 · see citing works
Maier, U., & Baumgartner, G. (1989) · The Journal of Urology · doi:10.1016/s0022-5347(17)40881-0 · Cited by 47 · see citing works
Pegylated Liposomal Doxorubicin: Scientific Rationale and Preclinical Pharmacology
Martin, F. J. (1997) · Cited by 43 · see citing works
Bruera, E. D., Neumann, C. M., Pituskin, E., Calder, K., & Hanson, J. (1999) · Annals of Oncology · doi:10.1023/a:1008331727535 · Cited by 39 · see citing works
Extracellular matrix hyaluronan is a determinant of the endothelial barrier
Qiao, R. L., Wang, H. S., Yan, W., Odekon, L. E., Vecchio, P. J. D., Smith, T. J., & Malik, A. B. (1995) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1995.269.1.c103 · Cited by 35 · see citing works
Chang, N. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4701 · Cited by 23 · see citing works
Adjuvant Therapy with Hyaluronidase Prior to Excision of Dermatofibrosarcoma Protuberans
Menon, P., Smith, K. J., Crittenden, J., & Skelton, H. G. (1999) · Dermatologic Surgery · doi:10.1046/j.1524-4725.1999.08148.x · Cited by 14 · see citing works
[Hyaluronidase in the therapy of malignant diseases].
Baumgartner, G. (1987) · PubMed · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195 · see citing works
“Local injection of hyaluronidase into osteosarcoma xenografts has been shown to decrease IFP (Brekken et al., 2000; Eikenes et al., 2005), although enforced overexpression of HA in thyroid and colon carcinoma xenografts did not increase it (Jacobson et al., 2003).”
BackgroundDanhier, F. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.11.015 · Cited by 1,288 · see citing works
Barua, S., & Mitragotri, S. (2014) · Nano Today · doi:10.1016/j.nantod.2014.04.008 · Cited by 1,270 · see citing works
Challenges and strategies in anti-cancer nanomedicine development: An industry perspective
Hare, J. I., Lammers, T., Ashford, M. B., Puri, S., Storm, G., & Barry, S. T. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.025 · Cited by 1,246 · see citing works
Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy
Henke, E., Nandigama, R., & Ergün, S. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2019.00160 · Cited by 1,142 · see citing works
“, 2013) and of liposomal DOX in osteosarcoma xenografts (Eikenes et al., 2005).”
BackgroundInfluentialKobayashi, H., Watanabe, R., & Choyke, P. L. (2014) · Theranostics · doi:10.7150/thno.7193 · Cited by 996 · see citing works
“(74) Most of these mediators are low molecular weight and thus, when injected systemically, will affect normal blood vessels in the vicinity of tumor, thus, facilitating extravasation not only within but also around tumors.”
BackgroundNanomedicine(s) under the Microscope
Duncan, R., & Gaspar, R. S. (2011) · Molecular Pharmaceutics · doi:10.1021/mp200394t · Cited by 985 · see citing works
Nichols, J. W., & Bae, Y. H. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.03.057 · Cited by 834 · see citing works
Delivery of Molecular and Nanoscale Medicine to Tumors: Transport Barriers and Strategies
Chauhan, V. P., Stylianopoulos, T., Boucher, Y., & Jain, R. K. (2011) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-061010-114300 · Cited by 597 · see citing works
Improving drug delivery to solid tumors: Priming the tumor microenvironment
Khawar, I. A., Kim, J. H., & Kuh, H.-J. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.12.018 · Cited by 533 · see citing works
A framework for designing delivery systems
Poon, W., Kingston, B. R., Ouyang, B., Ngo, W., & Chan, W. C. W. (2020) · Nature Nanotechnology · doi:10.1038/s41565-020-0759-5 · Cited by 526 · see citing works
Cell membrane-derived nanomaterials for biomedical applications
Fang, R. H., Jiang, Y., Fang, J. C., & Zhang, L. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.02.041 · Cited by 470 · see citing works
Platt, V. M., & Szoka, F. C. (2008) · Molecular Pharmaceutics · doi:10.1021/mp800024g · Cited by 455 · see citing works
El‐Sawy, H. S., Al-Abd, A. M., Ahmed, T. A., El‐Say, K. M., & Torchilin, V. P. (2018) · ACS Nano · doi:10.1021/acsnano.8b06104 · Cited by 435 · 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
Overchuk, M., & Zheng, G. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.10.024 · Cited by 383 · see citing works
The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics
Prakash, J., & Shaked, Y. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0002 · Cited by 391 · see citing works
Cairns, R. A., Papandreou, I., & Denko, N. C. (2006) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0002 · Cited by 370 · 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
Hyaluronidase To Enhance Nanoparticle-Based Photodynamic Tumor Therapy
Gong, H., Chao, Y., Xiang, J., Han, X., Song, G., Feng, L., Liu, J., Yang, G., Chen, Q., & Liu, Z. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b00068 · Cited by 322 · see citing works
Increased nanoparticle penetration in collagenase-treated multicellular spheroids.
Goodman, T. T., Olive, P. L., & Pun, S. H. (2007) · PubMed Central · Cited by 302 · see citing works
Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models
Thompson, C. B., Shepard, H. M., O'Connor, P. M., Kadhim, S., Jiang, P., Osgood, R. J., Bookbinder, L. H., Li, X., Sugarman, B. J., Connor, R. J., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0470 · Cited by 298 · see citing works
Stromal barriers and strategies for the delivery of nanomedicine to desmoplastic tumors
Miao, L., Lin, C. M., & Huang, L. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.017 · Cited by 264 · see citing works
Exploiting nanotechnology to overcome tumor drug resistance: Challenges and opportunities
Kirtane, A. R., Kalscheuer, S., & Panyam, J. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2013.09.001 · Cited by 262 · see citing works
Penetration and Uptake of Nanoparticles in 3D Tumor Spheroids
Tchoryk, A., Taresco, V., Argent, R. H., Ashford, M. B., Gellert, P. R., Stolnik, S., Grabowska, A. M., & Garnett, M. C. (2019) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.9b00136 · Cited by 247 · see citing works
Kanapathipillai, M., Brock, A., & Ingber, D. E. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.005 · Cited by 234 · see citing works
Liu, X., Lin, P. K., Perrett, I., Lin, J., Liao, Y., Chang, C. H., Jiang, J., Wu, N., Donahue, T. R., Wainberg, Z. A., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92284 · Cited by 222 · see citing works
Delivery of nanomedicines to extracellular and intracellular compartments of a solid tumor
Li, Y., Wang, J., Wientjes, M. G., & Au, J. L. ‐. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.04.006 · Cited by 221 · see citing works
“, liposomes) [80,81]; with a greater effect for collagenase [82].”
You, J., Zhang, R., Xiong, C., Zhong, M., Melancon, M. P., Gupta, S. K., Nick, A. M., Sood, A. K., & Li, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1003 · Cited by 215 · see citing works
“In addition to active targeting mediated by receptor ligands exemplified in this study, physiological and physical methods such as tumor priming, vascular disruption, degradation of the extracellular matrix, and vessel normalization may be used to improve tumor distribution of nanoparticles (25-29).”
MethodCurrent 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
Intratumoral Drug Delivery with Nanoparticulate Carriers
Holback, H., & Yeo, Y. (2011) · Pharmaceutical Research · doi:10.1007/s11095-010-0360-y · Cited by 186 · see citing works
“Collagenase (123, 124) and hyaluronidase (123, 125) have been used in conjunction with drug delivery”
BackgroundMethodInfluentialParodi, A., Haddix, S. G., Taghipour, N., Scaria, S., Taraballi, F., Cevenini, A., Yazdi, I. K., Corbo, C., Palomba, R., Khaled, S. Z., et al. (2014) · ACS Nano · doi:10.1021/nn502807n · Cited by 181 · see citing works
Nanoformulations for combination or cascade anticancer therapy
Miao, L., Guo, S., Lin, C. M., Liu, Q., & Huang, L. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.06.003 · Cited by 178 · see citing works
Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors
Middelburg, J., Kemper, K., Engelberts, P. J., Labrijn, A. F., Schuurman, J., & van Hall, T. (2021) · Cancers · doi:10.3390/cancers13020287 · Cited by 174 · see citing works
Sun, Y., & Davis, E. W. (2021) · Nanomaterials · doi:10.3390/nano11030746 · Cited by 180 · see citing works
Leveraging Physiology for Precision Drug Delivery
Sun, W., Hu, Q., Ji, W., Wright, G., & Gu, Z. (2017) · Physiological Reviews · doi:10.1152/physrev.00015.2016 · Cited by 169 · see citing works
Chemical Components for the Design of Temperature-Responsive Vesicles as Cancer Therapeutics
Al-Ahmady, Z. S., & Kostarelos, K. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00578 · Cited by 163 · 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
Au, J. L. ‐., Yeung, B. Z., Wientjes, M. G., Lu, Z., & Wientjes, M. G. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.12.002 · Cited by 161 · 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
Shim, M. K., Yang, S., Sun, I., & Kim, K. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114177 · Cited by 156 · see citing works
Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery
Zhang, B., Hu, Y., & Pang, Z. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00952 · Cited by 152 · see citing works
“Hyaluronidase was shown to induce a 4fold increase in the distribution of liposomal doxorubicin in a human osteosarcoma xenograft model (Eikenes et al., 2005).”
BackgroundKratz, F., & Warnecke, A. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.05.045 · Cited by 134 · see citing works
In Vivo Distribution of Polymeric Nanoparticles at the Whole-Body, Tumor, and Cellular Levels
Lee, H., Hoang, B., Fonge, H., Reilly, R. M., & Allen, C. J. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0068-z · Cited by 131 · see citing works
Tumor Priming Enhances Delivery and Efficacy of Nanomedicines
Lü, D., Wientjes, M. G., Lu, Z., & Au, J. L. ‐. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.121632 · Cited by 127 · see citing works
“Although increasing the gradient between MVP and IFP can promote the extravasation of albumin, antibodies, and liposomes (Eikenes et al., 2004, 2005; Tong et al., 2004), this is not a likely mechanism because paclitaxel simultaneously reduces MVP and IFP and does not alter the pressure gradient…”
BackgroundInfluentialEl‐Dakdouki, M. H., Zhu, D. C., El‐Boubbou, K., Kamat, M. N., Chen, J., Li, W., & Huang, X. (2012) · Biomacromolecules · doi:10.1021/bm300046h · Cited by 123 · see citing works
Ultrasound and microbubbles to beat barriers in tumors: Improving delivery of nanomedicine
Snipstad, S., Vikedal, K., Maardalen, M., Kurbatskaya, A., Sulheim, E., & Davies, C. D. L. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113847 · Cited by 120 · see citing works
Snipstad, S., Sulheim, E., Davies, C. D. L., MOONEN, C. T. W., Storm, G., Kiessling, F. M., Schmid, R., & Lammers, T. (2018) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2018.1547279 · Cited by 119 · see citing works
Targeting the tumor biophysical microenvironment to reduce resistance to immunotherapy
Zhang, T., Jia, Y., Yu, Y., Zhang, B., Xu, F., & Guo, H. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114319 · Cited by 116 · see citing works
Antifibrotic therapy to normalize the tumor microenvironment
Hauge, A., & Rofstad, E. K. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02376-y · Cited by 115 · see citing works
Therapeutic applications of collagenase (metalloproteases): A review
Alipour, H., Raz, A., Zakeri, S., & Djadid, N. D. (2016) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2016.07.017 · Cited by 113 · see citing works
Radionuclide carriers for targeting of cancer
Sofou, S. (2008) · International Journal of Nanomedicine · doi:10.2147/ijn.s2736 · Cited by 106 · see citing works
“Towards this goal, collagenase (Eikenes et al 2004) and hyaluronidase (Eikenes et al 2005) were evaluated in vivo on human osteosarcoma xenografts.”
Sato, Y., Note, Y., Maeki, M., Kaji, N., Baba, Y., Tokeshi, M., & Harashima, H. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.03.019 · Cited by 104 · see citing works
Therapeutic Targeting of Hyaluronan in the Tumor Stroma
Kultti, A. H., Li, X., Jiang, P., Thompson, C. B., Frost, G. I., & Shepard, H. M. (2012) · Cancers · doi:10.3390/cancers4030873 · Cited by 106 · see citing works
“In addition, previous preclinical studies [106–108] have attributed chemopotentiation by hyaluronidase to a reduction in tIFP, which facilitates enhanced drug penetration into HA-depleted tumors.”
BackgroundTumor extracellular matrix modulating strategies for enhanced antitumor therapy of nanomedicines
Li, M., Zhang, Y., Zhang, Q., & Li, J. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100364 · Cited by 105 · see citing works
Targeting endothelial permeability in the EPR effect
Lahooti, B., Akwii, R. G., Zahra, F. T., Sajib, M. S., Λάμπρου, Μ., Alobaida, A., Lionakis, M. S., Mattheolabakis, G., & Mikelis, C. M. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.07.039 · Cited by 109 · see citing works
Dhaliwal, A. K., & Zheng, G. (2019) · Theranostics · doi:10.7150/thno.37204 · Cited by 103 · see citing works
“Treatment with enzymes that digest the physical structure of the ECM, such as collagenase [29] and hyaluronidase [30,31,32,33], lower interstitial fluid pressure in tumors, while direct induction of apoptosis in cancer and stromal cells can reduce pressure on microvasculature to improve depth of penetration of agents…”
BackgroundJurj, A. M., Ionescu, C., Berindan‐Neagoe, I., & Braicu, C. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02484-1 · Cited by 109 · see citing works
Cancer Cell Death Enhances the Penetration and Efficacy of Oncolytic Herpes Simplex Virus in Tumors
Nagano, S., Perentes, J. Y., Jain, R. K., & Boucher, Y. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6193 · Cited by 104 · see citing works
“Although hyaluronan is thought to hinder the movement of large molecules (19, 20, 25), paclitaxel-TRAIL pretreatment still improved the viral dispersion, suggesting that hyaluronan was not Figure 5.”
BackgroundBaronzio, G., Parmar, G., & Baronzio, M. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00165 · Cited by 100 · see citing works
Immunoliposomes in clinical oncology: State of the art and future perspectives
Merino, M., Zalba, S., & Garrido, M. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.02.015 · Cited by 100 · see citing works
Pulsed Ultrasound Enhances Nanoparticle Penetration into Breast Cancer Spheroids
Grainger, S. J., Serna, J. V., Sunny, S., Zhou, Y., Deng, C. X., & ElSayed, M. E. H. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100280b · Cited by 99 · see citing works
Physical and chemical modifications of collagen gels: Impact on diffusion
Erikson, A., Andersen, H. N., Næss, S. N., Sikorski, P., & Davies, C. D. L. (2007) · Biopolymers · doi:10.1002/bip.20874 · Cited by 91 · 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
Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment
Sun, B., Hyun, H., Li, L., & Wang, A. Z. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-0424-4 · Cited by 91 · see citing works
“The DOX-encapsulated and IND-conjugated liposomes (DOX/IND liposomes) induce ICD and increase phosphorylation of S6 kinase in the mTOR pathway, reversing the immunosuppressive activity of IDO; furthermore, the pharmacokinetics of DOX or IND were improved in the 4T1 tumor model, demonstrating the use of nanoliposomes t…”
BackgroundLocoregional drug delivery for cancer therapy: Preclinical progress and clinical translation
Shaha, S., Rodrigues, D., & Mitragotri, S. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.01.072 · Cited by 90 · see citing works
Improving the distribution of Doxil® in the tumor matrix by depletion of tumor hyaluronan
Kohli, A. G., Kivimäe, S., Tiffany, M. R., & Szoka, F. C. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.05.019 · Cited by 87 · see citing works
“In contrast to PEGPHG20 treatment, treatment with L-MU-P does not alter the EPR effect and enhance tumor uptake of nanoparticles [56].”
Al-Ahmady, Z. S., Chaloin, O., & Kostarelos, K. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.10.013 · Cited by 86 · see citing works
Marcucci, F., & Corti, A. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.09.007 · Cited by 87 · see citing works
Improving Delivery and Efficacy of Nanomedicines in Solid Tumors: Role of Tumor Priming
Wang, J., Lu, Z., Gao, Y., Wientjes, M. G., & Au, J. L. ‐. (2011) · Nanomedicine · doi:10.2217/nnm.11.141 · Cited by 85 · see citing works
Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex
Kato, M., Hattori, Y., Kubo, M., & Maitani, Y. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.12.015 · Cited by 85 · see citing works
Drug distribution in tumors: Mechanisms, role in drug resistance, and methods for modification
Paolo, A. D., & Bocci, G. (2007) · Current Oncology Reports · doi:10.1007/s11912-007-0006-3 · Cited by 85 · 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
Mechanisms of the ultrasound-mediated intracellular delivery of liposomes and dextrans
Afadzi, M., Strand, S. P., Nilssen, E. A., Måsøy, S., Johansen, T. F., Hansen, R., Angelsen, B., & Davies, C. D. L. (2012) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2013.2534 · Cited by 82 · see citing works
“These improvements may be achieved by treating the tumor chemically using enzymes [8], [9] or physically by radiation [6] or ultrasound [10]–[12].”
BackgroundNanomedicine 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
Challenges to effective cancer nanotheranostics
Melancon, M. P., Stafford, R. J., & Li, C. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.07.045 · Cited by 79 · see citing works
“Also, degradation of the extracellular matrix by collagenase or hyaluronidase increased the distribution of a monoclonal antibody and liposomal doxorubicin in tumor twofold to fourfold [17, 18].”
BackgroundCAR T Cell Therapy of Non-hematopoietic Malignancies: Detours on the Road to Clinical Success
Long, K. B., Young, R. M., Boesteanu, A. C., Suhoski, M. M., Melenhorst, J. J., Lacey, S. F., Degaramo, D. A., Levine, B. L., & Fraietta, J. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02740 · Cited by 78 · see citing works
Liu, J., Tian, L., Zhang, R., Dong, Z., Wang, H., & Liu, Z. (2018) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b17684 · Cited by 74 · see citing works
Boeckelmann, L., & Schumacher, U. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1702974 · Cited by 76 · see citing works
Stapleton, S., Milosevic, M., Tannock, I. F., Allen, C. J., & Jaffray, D. A. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.06.008 · Cited by 73 · see citing works
Luo, J., Gong, T., & Ma, L. (2020) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2020.116887 · Cited by 72 · see citing works
Emerging nanomedicines for anti-stromal therapy against desmoplastic tumors
Han, X., Xu, Y., Geranpayehvaghei, M., Anderson, G. J., Li, Y., & Nie, G. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119745 · Cited by 71 · see citing works
Controlled Extracellular Matrix Degradation in Breast Cancer Tumors Improves Therapy by Trastuzumab
Beyer, I., Li, Z., Persson, J., Liu, Y., van Rensburg, R., Yumul, R., Zhang, X., Hung, M., & Lieber, A. (2010) · Molecular Therapy · doi:10.1038/mt.2010.256 · Cited by 70 · see citing works
Pharmacokinetics and pharmacodynamics of liposomal chemophototherapy with short drug-light intervals
Luo, D., Carter, K. A., Molins, E. A. G., Straubinger, N. L., Geng, J., Shao, S., Jusko, W. J., Straubinger, R. M., & Lovell, J. F. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.01.030 · Cited by 70 · see citing works
Hyaluronan degrading silica nanoparticles for skin cancer therapy
Scodeller, P., Catalano, P. N., Salguero, N., Durán, H., Wolosiuk, A., & Soler‐Illia, G. J. A. A. (2013) · Nanoscale · doi:10.1039/c3nr02787b · Cited by 69 · see citing works
Pharmacokinetic strategies to improve drug penetration and entrapment within solid tumors
Al-Abd, A. M., Aljehani, Z. K., Gazzaz, R. W., Fakhri, S. H., Jabbad, A. H., Alahdal, A. M., & Torchilin, V. P. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.055 · Cited by 66 · see citing works
Surface-Active Liposomes for Targeted Cancer Therapy
Sofou, S. (2007) · Nanomedicine · doi:10.2217/17435889.2.5.711 · Cited by 66 · see citing works
Morosi, L., Meroni, M., Ubezio, P., Nerini, I. F., Minoli, L., Porcu, L., Panini, N., Colombo, M., Blouw, B., Kang, D. W., et al. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02070-x · Cited by 64 · see citing works
Malhotra, S., Dumoga, S., & Singh, N. (2022) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1776 · Cited by 67 · see citing works
Gazzano, E., Buondonno, I., Marengo, A., Rolando, B., Chegaev, K. Y., Kopecka, J., Saponara, S., Sorge, M., Hattinger, C. M., Gasco, A., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.029 · Cited by 64 · see citing works
Hak, S., Reitan, N. K., Haraldseth, O., & Davies, C. D. L. (2010) · Angiogenesis · doi:10.1007/s10456-010-9176-y · Cited by 62 · see citing works
“Enzymatic degradation of tumor ECM components induces a transcapillary pressure gradient and has been found to increase the diffusion of macromolecules through the tumor interstitium [24, 26, 94–98].”
BackgroundEikenes, L., Tufto, I., Schnell, E. A., Bjørkøy, A., & Davies, C. D. L. (2010) · PubMed · Cited by 62 · see citing works
Geretti, E., Leonard, S. C., Dumont, N., Lee, H., Zheng, J., Souza, R. D., Gaddy, D. F., Espelin, C. W., Jaffray, D. A., Moyo, V. M., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0314 · Cited by 61 · see citing works
Ikeda-Imafuku, M., Gao, Y., Shaha, S., Wang, L., Park, K. S., Nakajima, M., Adebowale, O., & Mitragotri, S. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.007 · Cited by 61 · see citing works
Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors
Paresishvili, T., & Kakabadze, Z. (2023) · Oncology Reviews · doi:10.3389/or.2023.10577 · Cited by 59 · see citing works
Čemažar, M., Golzio, M., Serša, G., Escoffre, J., Coer, A., Vidic, S., & Teissié, J. (2011) · Human Gene Therapy · doi:10.1089/hum.2011.073 · Cited by 58 · see citing works
“Hyaluronidase led to improved distribution and therapeutic efficacy of chemotherapeutic drugs (Eikenes et al. , 2005).”
Extracellular matrix in cancer progression and therapy
He, X., Lee, B., & Jiang, Y. (2022) · Medical Review · doi:10.1515/mr-2021-0028 · Cited by 56 · see citing works
Nanomedicines in the future of pediatric therapy.
Sosnik, A., & Carcaboso, A. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.05.004 · Cited by 54 · see citing works
Effective targeting of the tumor microenvironment for cancer therapy.
Jiang, P., Li, X., Thompson, C. B., Huang, Z., Araiza, F., Osgood, R. J., Wei, G., Feldmann, M., Frost, G. I., & Shepard, H. M. (2012) · PubMed · Cited by 56 · see citing works
Chen, E., Han, S., Song, B., Xu, L. X., Yuan, H., Liang, M., & Sun, Y. Y. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s257164 · Cited by 56 · see citing works
- Authors
- Eikenes, L., Tari, M., Tufto, I., Bruland, Ø. S., & de Lange Davies, C.
- Affiliations
- Norwegian University of Science and Technology (NO)
- University of Oslo (NO)
- Corresponding author
- Eikenes, L
- Venue
- British Journal of Cancer
- Published
- 2005-06-07
- Volume
- 93
- Issue
- 1
- Pages
- 81-88
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2361478
- OpenAlex
- W1985957186
- Cited by
- 221
- References
- 41
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 19 · 2021: 13 · 2020: 17 · 2019: 13 · 2018: 15 · 2017: 11 · 2016: 14 · 2015: 11 · 2014: 16 · 2013: 10 · 2012: 12
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Kreftforeningen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- hyaluronidase, liposomal doxorubicin, pegylated liposomal doxorubicin, osteosarcoma, interstitial fluid pressure, extracellular matrix degradation, microvascular pressure, tumor xenografts, drug delivery enhancement
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Doxorubicin, Female, Humans, Hyaluronoglucosaminidase, Liposomes, Mice, Inbred BALB C, Osteosarcoma, Transplantation, Heterologous, Microscopy, Confocal, Mice
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