Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles: Effects of drug concentration on tumor uptake

Fangyuan Xiong, Sabnis Nirupama, Shashank R. Sirsi, Andras G. Lacko, Kenneth Hoyt

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

In cancer treatment, there is a need to improve chemotherapeutic drug uptake at the local tumor site to both enhance dose efficacy and minimize any toxic side effects. It is well known now that stably cavitating microbubbles (MBs) in an ultrasound (US) field can increase the permeability of tumor blood vessel walls. This consequently can enhance the extravasation and accumulation of a circulating anticancer drug. Reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via the overexpressed scavenger receptor class B type 1 (SR-B1). The goal of this study was to evaluate the potential of US-stimulated drug delivery for improving tumor uptake of rHDL NPs that were preloaded with IR-780 dye (i.e., drug surrogate). Mice implanted with human breast cancer cells were divided into five groups: control, and low- or high-dose rHDL NPs ± US therapy. In vivo fluorescence optical imaging was used to quantify intratumoral NP accumulation at baseline and again at 1, 30, 60 min, 24 and 48 h after dosing. At 48 hours after treatment, tumors were resected and subjected to a fluorescent dye extraction study. Results of in vivo optical imaging revealed that the US therapy group animals exhibited stronger rHDL dye localization in the tumor area comparing to non-US groups. Moreover, in the dye extraction study, higher dye levels were detected in the US therapy groups compared to the non-US exposed animals given the same rHDL doses. Meanwhile, administration of a higher dose of rHDL NPs promoted dye accumulation in tumor sites. Overall, US-stimulated drug delivery can noninvasively promote the improved local tumor uptake of rHDL NP vectors.

Original languageEnglish
Title of host publication2017 IEEE International Ultrasonics Symposium, IUS 2017
PublisherIEEE Computer Society
ISBN (Electronic)9781538633830
DOIs
StatePublished - 31 Oct 2017
Event2017 IEEE International Ultrasonics Symposium, IUS 2017 - Washington, United States
Duration: 6 Sep 20179 Sep 2017

Other

Other2017 IEEE International Ultrasonics Symposium, IUS 2017
CountryUnited States
CityWashington
Period6/09/179/09/17

Fingerprint

lipoproteins
delivery
drugs
tumors
nanoparticles
dyes
dosage
therapy
animals
cancer
blood vessels
breast
mice
permeability
fluorescence

Keywords

  • Cancer therapy
  • Microbubble contrast agents
  • Nanoparticles
  • Optical imaging
  • Reconstituted high-density lipoprotein
  • Ultrasound-stimulated drug delivery

Cite this

Xiong, F., Nirupama, S., Sirsi, S. R., Lacko, A. G., & Hoyt, K. (2017). Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles: Effects of drug concentration on tumor uptake. In 2017 IEEE International Ultrasonics Symposium, IUS 2017 [8092663] IEEE Computer Society. https://doi.org/10.1109/ULTSYM.2017.8092663
Xiong, Fangyuan ; Nirupama, Sabnis ; Sirsi, Shashank R. ; Lacko, Andras G. ; Hoyt, Kenneth. / Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles : Effects of drug concentration on tumor uptake. 2017 IEEE International Ultrasonics Symposium, IUS 2017. IEEE Computer Society, 2017.
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abstract = "In cancer treatment, there is a need to improve chemotherapeutic drug uptake at the local tumor site to both enhance dose efficacy and minimize any toxic side effects. It is well known now that stably cavitating microbubbles (MBs) in an ultrasound (US) field can increase the permeability of tumor blood vessel walls. This consequently can enhance the extravasation and accumulation of a circulating anticancer drug. Reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via the overexpressed scavenger receptor class B type 1 (SR-B1). The goal of this study was to evaluate the potential of US-stimulated drug delivery for improving tumor uptake of rHDL NPs that were preloaded with IR-780 dye (i.e., drug surrogate). Mice implanted with human breast cancer cells were divided into five groups: control, and low- or high-dose rHDL NPs ± US therapy. In vivo fluorescence optical imaging was used to quantify intratumoral NP accumulation at baseline and again at 1, 30, 60 min, 24 and 48 h after dosing. At 48 hours after treatment, tumors were resected and subjected to a fluorescent dye extraction study. Results of in vivo optical imaging revealed that the US therapy group animals exhibited stronger rHDL dye localization in the tumor area comparing to non-US groups. Moreover, in the dye extraction study, higher dye levels were detected in the US therapy groups compared to the non-US exposed animals given the same rHDL doses. Meanwhile, administration of a higher dose of rHDL NPs promoted dye accumulation in tumor sites. Overall, US-stimulated drug delivery can noninvasively promote the improved local tumor uptake of rHDL NP vectors.",
keywords = "Cancer therapy, Microbubble contrast agents, Nanoparticles, Optical imaging, Reconstituted high-density lipoprotein, Ultrasound-stimulated drug delivery",
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Xiong, F, Nirupama, S, Sirsi, SR, Lacko, AG & Hoyt, K 2017, Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles: Effects of drug concentration on tumor uptake. in 2017 IEEE International Ultrasonics Symposium, IUS 2017., 8092663, IEEE Computer Society, 2017 IEEE International Ultrasonics Symposium, IUS 2017, Washington, United States, 6/09/17. https://doi.org/10.1109/ULTSYM.2017.8092663

Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles : Effects of drug concentration on tumor uptake. / Xiong, Fangyuan; Nirupama, Sabnis; Sirsi, Shashank R.; Lacko, Andras G.; Hoyt, Kenneth.

2017 IEEE International Ultrasonics Symposium, IUS 2017. IEEE Computer Society, 2017. 8092663.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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T2 - Effects of drug concentration on tumor uptake

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AU - Nirupama, Sabnis

AU - Sirsi, Shashank R.

AU - Lacko, Andras G.

AU - Hoyt, Kenneth

PY - 2017/10/31

Y1 - 2017/10/31

N2 - In cancer treatment, there is a need to improve chemotherapeutic drug uptake at the local tumor site to both enhance dose efficacy and minimize any toxic side effects. It is well known now that stably cavitating microbubbles (MBs) in an ultrasound (US) field can increase the permeability of tumor blood vessel walls. This consequently can enhance the extravasation and accumulation of a circulating anticancer drug. Reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via the overexpressed scavenger receptor class B type 1 (SR-B1). The goal of this study was to evaluate the potential of US-stimulated drug delivery for improving tumor uptake of rHDL NPs that were preloaded with IR-780 dye (i.e., drug surrogate). Mice implanted with human breast cancer cells were divided into five groups: control, and low- or high-dose rHDL NPs ± US therapy. In vivo fluorescence optical imaging was used to quantify intratumoral NP accumulation at baseline and again at 1, 30, 60 min, 24 and 48 h after dosing. At 48 hours after treatment, tumors were resected and subjected to a fluorescent dye extraction study. Results of in vivo optical imaging revealed that the US therapy group animals exhibited stronger rHDL dye localization in the tumor area comparing to non-US groups. Moreover, in the dye extraction study, higher dye levels were detected in the US therapy groups compared to the non-US exposed animals given the same rHDL doses. Meanwhile, administration of a higher dose of rHDL NPs promoted dye accumulation in tumor sites. Overall, US-stimulated drug delivery can noninvasively promote the improved local tumor uptake of rHDL NP vectors.

AB - In cancer treatment, there is a need to improve chemotherapeutic drug uptake at the local tumor site to both enhance dose efficacy and minimize any toxic side effects. It is well known now that stably cavitating microbubbles (MBs) in an ultrasound (US) field can increase the permeability of tumor blood vessel walls. This consequently can enhance the extravasation and accumulation of a circulating anticancer drug. Reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via the overexpressed scavenger receptor class B type 1 (SR-B1). The goal of this study was to evaluate the potential of US-stimulated drug delivery for improving tumor uptake of rHDL NPs that were preloaded with IR-780 dye (i.e., drug surrogate). Mice implanted with human breast cancer cells were divided into five groups: control, and low- or high-dose rHDL NPs ± US therapy. In vivo fluorescence optical imaging was used to quantify intratumoral NP accumulation at baseline and again at 1, 30, 60 min, 24 and 48 h after dosing. At 48 hours after treatment, tumors were resected and subjected to a fluorescent dye extraction study. Results of in vivo optical imaging revealed that the US therapy group animals exhibited stronger rHDL dye localization in the tumor area comparing to non-US groups. Moreover, in the dye extraction study, higher dye levels were detected in the US therapy groups compared to the non-US exposed animals given the same rHDL doses. Meanwhile, administration of a higher dose of rHDL NPs promoted dye accumulation in tumor sites. Overall, US-stimulated drug delivery can noninvasively promote the improved local tumor uptake of rHDL NP vectors.

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KW - Microbubble contrast agents

KW - Nanoparticles

KW - Optical imaging

KW - Reconstituted high-density lipoprotein

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Xiong F, Nirupama S, Sirsi SR, Lacko AG, Hoyt K. Ultrasound-stimulated drug delivery of reconstituted high-density lipoprotein nanoparticles: Effects of drug concentration on tumor uptake. In 2017 IEEE International Ultrasonics Symposium, IUS 2017. IEEE Computer Society. 2017. 8092663 https://doi.org/10.1109/ULTSYM.2017.8092663