Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain

Andrew S. Gdowski; Amalendu Ranjan; Marjana R. Sarker; Jamboor K. Vishwanatha

doi:10.2217/nnm-2017-0190

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain

Andrew S. Gdowski, Amalendu Ranjan, Marjana R. Sarker, Jamboor K. Vishwanatha

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Aim: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Materials & methods: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. Results: This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. Conclusion: This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Original language	English
Pages (from-to)	2083-2095
Number of pages	13
Journal	Nanomedicine
Volume	12
Issue number	17
DOIs	https://doi.org/10.2217/nnm-2017-0190
State	Published - Sep 2017

Keywords

bone metastasis
cabazitaxel
polymeric nanoparticle
prostate cancer
targeted therapeutic

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title = "Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain",

abstract = "Aim: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Materials & methods: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. Results: This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. Conclusion: This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.",

keywords = "bone metastasis, cabazitaxel, polymeric nanoparticle, prostate cancer, targeted therapeutic",

author = "Gdowski, {Andrew S.} and Amalendu Ranjan and Sarker, {Marjana R.} and Vishwanatha, {Jamboor K.}",

note = "Funding Information: This work was supported by grant awards from National Institutes of Health number R21CA194295 (to JK Vishwanatha) and 1P20 MD006882 (JK Vishwanatha), and the American Medical Association (A Gdowski) and the American Urological Association (A Gdowski). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: {\textcopyright} 2017 Andrew S Gdowski.",

year = "2017",

month = sep,

doi = "10.2217/nnm-2017-0190",

language = "English",

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pages = "2083--2095",

journal = "Nanomedicine",

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T1 - Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain

AU - Gdowski, Andrew S.

AU - Ranjan, Amalendu

AU - Sarker, Marjana R.

AU - Vishwanatha, Jamboor K.

N1 - Funding Information: This work was supported by grant awards from National Institutes of Health number R21CA194295 (to JK Vishwanatha) and 1P20 MD006882 (JK Vishwanatha), and the American Medical Association (A Gdowski) and the American Urological Association (A Gdowski). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: © 2017 Andrew S Gdowski.

PY - 2017/9

Y1 - 2017/9

N2 - Aim: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Materials & methods: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. Results: This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. Conclusion: This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

AB - Aim: The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Materials & methods: Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. Results: This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. Conclusion: This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

KW - bone metastasis

KW - cabazitaxel

KW - polymeric nanoparticle

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KW - targeted therapeutic

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Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain

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Keywords

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