Abstract

Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remains high in incidence and challenging to manage. Here, we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation, and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity, and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactant-based formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

Original languageEnglish (US)
JournalMolecular Pharmaceutics
DOIs
StatePublished - Jan 1 2019

Fingerprint

docetaxel
Alendronate
Bone Neoplasms
Micelles
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Nanomedicine
Bone Development
Osteoclasts
Therapeutics
Surface-Active Agents
Carcinogenesis
Animal Models
Pharmacokinetics
Incidence

Keywords

  • bone targeting
  • breast cancer bone metastasis
  • nanomedicine
  • polymeric micelles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Alendronate-Modified Polymeric Micelles for the Treatment of Breast Cancer Bone Metastasis. / Liu, Tong; Romanova, Svetlana; Wang, Shuo; Hyun, Megan A; Zhang, Chi; Cohen, Samuel Monroe; Singh, Rakesh K; Bronich, Tatiana K.

In: Molecular Pharmaceutics, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Wang, Shuo

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AU - Zhang, Chi

AU - Cohen, Samuel Monroe

AU - Singh, Rakesh K

AU - Bronich, Tatiana K

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N2 - Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remains high in incidence and challenging to manage. Here, we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation, and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity, and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactant-based formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

AB - Although the prognosis of patients with breast cancer continues to improve, breast cancer metastasis to bones remains high in incidence and challenging to manage. Here, we report the development of bone-homing alendronate (ALN)-anchored biodegradable polymeric micelles for the targeted treatment of metastatic cancer to bone. These micelles exhibited bone protective capacity including the recruitment, differentiation, and resorption activity of the osteoclasts. Encapsulation of docetaxel (DTX), the first-line chemotherapeutic for treatment of metastatic breast cancer, in ALN-modified micelles results in a sustained release, enhanced cytotoxicity, and improved pharmacokinetics. In the syngeneic animal model of late-stage disseminated breast cancer bone metastasis, the treatment with targeted DTX-loaded micelles attenuated the tumorigenesis and significantly improved animal lifespan compared to the conventional surfactant-based formulation (free DTX). These findings indicate potential applications of the osteotropic nanomedicines for bone metastasis treatment.

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