Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer

Sanjay I. Thamake, Sangram L. Raut, Zygmunt Gryczynski, Amalendu P. Ranjan, Jamboor K. Vishwanatha

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Delivery of therapeutic agents to bone is crucial in several diseases such as osteoporosis, Paget's disease, myeloproliferative diseases, multiple myeloma as well as skeletal metastasizing cancers. Prevention of cancer growth and lowering the cancer induced bone resorption is important in the treatment of bone metastasizing cancers. Keeping in mind the low diffusivity and availability of cell surface targets on cancer cells, we designed a targeted system to deliver chemotherapeutic agents to the bone microenvironment as an approach to tissue targeting using alendronate (Aln). We co-encapsulated curcumin and bortezomib in the PLGA nanoparticles to further enhance the therapeutic efficiency and overall clinical outcome. These multifunctional nanoparticles were characterized for particle size, morphology and drug encapsulation. The particles were spherical with smooth surface and had particle size of 235 ± 70.30 nm. We validated the bone targeting ability of these nanoparticles in vitro. Curcumin and bortezomib are known to have synergistic effect in inhibition of growth of cancer; however there was no synergism in the anti-osteoclastogenic activity of these agents. Surprisingly, curcumin by itself had significant inhibition of osteclastogenic activity. In vivo non-invasive bioimaging showed higher localization of Aln-coated nanoparticles to the bone compared to control groups, which was further confirmed by histological analysis. Aln-coated nanoparticles protected bone resorption and decreased the rate of tumor growth as compared to control groups in an intraosseous model of bone metastasis. Our data show efficient attachment of Aln on the surface of nanoparticles which could be used as a drug carrier for preferential delivery of multiple therapeutic agents to bone microenvironment.

Original languageEnglish
Pages (from-to)7164-7173
Number of pages10
JournalBiomaterials
Volume33
Issue number29
DOIs
StatePublished - 1 Oct 2012

Fingerprint

Alendronate
Nanoparticles
Bone
Breast Neoplasms
Bone and Bones
Curcumin
Acids
Bone Neoplasms
Neoplasms
Bone Resorption
Particle Size
Growth
Control Groups
Drug Carriers
Therapeutics
Multiple Myeloma
Particle size
Osteoporosis
polylactic acid-polyglycolic acid copolymer
Milk

Keywords

  • Alendronate
  • Bone targeting
  • Bortezomib
  • Breast cancer
  • Curcumin
  • Nanoparticles

Cite this

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title = "Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer",
abstract = "Delivery of therapeutic agents to bone is crucial in several diseases such as osteoporosis, Paget's disease, myeloproliferative diseases, multiple myeloma as well as skeletal metastasizing cancers. Prevention of cancer growth and lowering the cancer induced bone resorption is important in the treatment of bone metastasizing cancers. Keeping in mind the low diffusivity and availability of cell surface targets on cancer cells, we designed a targeted system to deliver chemotherapeutic agents to the bone microenvironment as an approach to tissue targeting using alendronate (Aln). We co-encapsulated curcumin and bortezomib in the PLGA nanoparticles to further enhance the therapeutic efficiency and overall clinical outcome. These multifunctional nanoparticles were characterized for particle size, morphology and drug encapsulation. The particles were spherical with smooth surface and had particle size of 235 ± 70.30 nm. We validated the bone targeting ability of these nanoparticles in vitro. Curcumin and bortezomib are known to have synergistic effect in inhibition of growth of cancer; however there was no synergism in the anti-osteoclastogenic activity of these agents. Surprisingly, curcumin by itself had significant inhibition of osteclastogenic activity. In vivo non-invasive bioimaging showed higher localization of Aln-coated nanoparticles to the bone compared to control groups, which was further confirmed by histological analysis. Aln-coated nanoparticles protected bone resorption and decreased the rate of tumor growth as compared to control groups in an intraosseous model of bone metastasis. Our data show efficient attachment of Aln on the surface of nanoparticles which could be used as a drug carrier for preferential delivery of multiple therapeutic agents to bone microenvironment.",
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Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer. / Thamake, Sanjay I.; Raut, Sangram L.; Gryczynski, Zygmunt; Ranjan, Amalendu P.; Vishwanatha, Jamboor K.

In: Biomaterials, Vol. 33, No. 29, 01.10.2012, p. 7164-7173.

Research output: Contribution to journalArticle

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T1 - Alendronate coated poly-lactic-co-glycolic acid (PLGA) nanoparticles for active targeting of metastatic breast cancer

AU - Thamake, Sanjay I.

AU - Raut, Sangram L.

AU - Gryczynski, Zygmunt

AU - Ranjan, Amalendu P.

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