Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy

Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research...
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Autor*in:	Kalra, Jessica [verfasserIn] Baker, Jennifer [verfasserIn] Sun, XuXin [verfasserIn] Kyle, Alastair [verfasserIn] Minchinton, Andrew [verfasserIn] Bally, Marcel B. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Liposomes Enhanced permeability and retention effect Metastases/metastasis Tumor microenvironment Inter- and intra-tumor heterogeneity Pre-clinical models Translational research

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - BioMed Central, 2003, 22(2024), 1 vom: 03. Juli
Übergeordnetes Werk:	volume:22 ; year:2024 ; number:1 ; day:03 ; month:07

Links:	Volltext

DOI / URN:	10.1186/s12967-024-05428-9

Katalog-ID:	SPR056463022

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520			\|a Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.
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allfields	10.1186/s12967-024-05428-9 doi (DE-627)SPR056463022 (SPR)s12967-024-05428-9-e DE-627 ger DE-627 rakwb eng 610 VZ Kalra, Jessica verfasserin (orcid)0009-0004-3383-6901 aut Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213 Baker, Jennifer verfasserin aut Sun, XuXin verfasserin aut Kyle, Alastair verfasserin aut Minchinton, Andrew verfasserin aut Bally, Marcel B. verfasserin aut Enthalten in Journal of translational medicine BioMed Central, 2003 22(2024), 1 vom: 03. Juli (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:22 year:2024 number:1 day:03 month:07 https://dx.doi.org/10.1186/s12967-024-05428-9 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 03 07
spelling	10.1186/s12967-024-05428-9 doi (DE-627)SPR056463022 (SPR)s12967-024-05428-9-e DE-627 ger DE-627 rakwb eng 610 VZ Kalra, Jessica verfasserin (orcid)0009-0004-3383-6901 aut Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213 Baker, Jennifer verfasserin aut Sun, XuXin verfasserin aut Kyle, Alastair verfasserin aut Minchinton, Andrew verfasserin aut Bally, Marcel B. verfasserin aut Enthalten in Journal of translational medicine BioMed Central, 2003 22(2024), 1 vom: 03. Juli (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:22 year:2024 number:1 day:03 month:07 https://dx.doi.org/10.1186/s12967-024-05428-9 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 03 07
allfields_unstemmed	10.1186/s12967-024-05428-9 doi (DE-627)SPR056463022 (SPR)s12967-024-05428-9-e DE-627 ger DE-627 rakwb eng 610 VZ Kalra, Jessica verfasserin (orcid)0009-0004-3383-6901 aut Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213 Baker, Jennifer verfasserin aut Sun, XuXin verfasserin aut Kyle, Alastair verfasserin aut Minchinton, Andrew verfasserin aut Bally, Marcel B. verfasserin aut Enthalten in Journal of translational medicine BioMed Central, 2003 22(2024), 1 vom: 03. Juli (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:22 year:2024 number:1 day:03 month:07 https://dx.doi.org/10.1186/s12967-024-05428-9 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 03 07
allfieldsGer	10.1186/s12967-024-05428-9 doi (DE-627)SPR056463022 (SPR)s12967-024-05428-9-e DE-627 ger DE-627 rakwb eng 610 VZ Kalra, Jessica verfasserin (orcid)0009-0004-3383-6901 aut Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213 Baker, Jennifer verfasserin aut Sun, XuXin verfasserin aut Kyle, Alastair verfasserin aut Minchinton, Andrew verfasserin aut Bally, Marcel B. verfasserin aut Enthalten in Journal of translational medicine BioMed Central, 2003 22(2024), 1 vom: 03. Juli (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:22 year:2024 number:1 day:03 month:07 https://dx.doi.org/10.1186/s12967-024-05428-9 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 03 07
allfieldsSound	10.1186/s12967-024-05428-9 doi (DE-627)SPR056463022 (SPR)s12967-024-05428-9-e DE-627 ger DE-627 rakwb eng 610 VZ Kalra, Jessica verfasserin (orcid)0009-0004-3383-6901 aut Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213 Baker, Jennifer verfasserin aut Sun, XuXin verfasserin aut Kyle, Alastair verfasserin aut Minchinton, Andrew verfasserin aut Bally, Marcel B. verfasserin aut Enthalten in Journal of translational medicine BioMed Central, 2003 22(2024), 1 vom: 03. Juli (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:22 year:2024 number:1 day:03 month:07 https://dx.doi.org/10.1186/s12967-024-05428-9 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2024 1 03 07
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Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. 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author	Kalra, Jessica
spellingShingle	Kalra, Jessica ddc 610 misc Liposomes misc Enhanced permeability and retention effect misc Metastases/metastasis misc Tumor microenvironment misc Inter- and intra-tumor heterogeneity misc Pre-clinical models misc Translational research Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
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topic_title	610 VZ Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy Liposomes (dpeaa)DE-He213 Enhanced permeability and retention effect (dpeaa)DE-He213 Metastases/metastasis (dpeaa)DE-He213 Tumor microenvironment (dpeaa)DE-He213 Inter- and intra-tumor heterogeneity (dpeaa)DE-He213 Pre-clinical models (dpeaa)DE-He213 Translational research (dpeaa)DE-He213
topic	ddc 610 misc Liposomes misc Enhanced permeability and retention effect misc Metastases/metastasis misc Tumor microenvironment misc Inter- and intra-tumor heterogeneity misc Pre-clinical models misc Translational research
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title	Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
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title_full	Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
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title_sort	accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
title_auth	Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
abstract	Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. © The Author(s) 2024
abstractGer	Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. © The Author(s) 2024
abstract_unstemmed	Background The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. Conclusion These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect. © The Author(s) 2024
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title_short	Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy
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Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. Methods Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-$ 1^{mkate} $, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. Results A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-$ 1^{mkate} $ models. 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Accumulation of liposomes in metastatic tumor sites is not necessary for anti-cancer drug efficacy

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