Engineered Nanomedicine with Alendronic Acid Corona Improves Targeting to Osteosarcoma.
We engineered nanomedicine with the stealth corona made up of densely packed bone seeking ligand, alendronic acid. In a typical nanoconstruct, alendronic acid is conjugated with hydrophilic head moiety of phospholipid that has an ability to self-assemble with hydrophobic polymeric core through its hydrophobic long carbon-chain. Proposed nanomedicine has three distinct compartments namely; poly(l-lactic-co-glycolic acid) polymeric core acting as a drug reservoir and skeleton of the nanoconstruct, phospholipid monolayer covers the core acting as a diffusion barrier, and a densely packed alendronic acid corona acting as a stabilizer and targeting moiety. Thus engineered nanomedicine attain spherical entity with ~90 ± 6 nm having negative zeta potential, -37.7 ± 2 mV, and has an ability to load 7 ± 0.3 wt% of doxorubicin. In-vitro bone targeting efficiency of nanomedicine was studied using hydroxyapatite crystals as a bone model, and found significant accumulation of nanoparticle in the crystals. Moreover, cellular internalization studies with mouse osteosarcoma confirm the selectivity of nanomedicine when compared to its internalization in non-targeted mouse melanoma. This nanomedicine shows prolong stability in serum and deliver the drug into the cell exhibiting an IC50 of 3.7 μM. Given the strong interacting property of alendronic acid with bone, the proposed nanomedicine hold promises in delivering drug to bone microenvironment.
Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA.|Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.
Tuyen Duong Thanh
TD
Nguyen
Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA.|Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.|Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA.
Arunkumar
A
Pitchaimani
Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA.|Nanotechnology Innovation Center of Kansas State (NICKS), Kansas State University, Manhattan, KS 66506, USA.
Santosh
S
Aryal
D019386:Alendronate / Q000008:administration & dosage*; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002118:Calcium / Q000737:chemistry; D002469:Cell Separation; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008055:Lipids; D009682:Magnetic Resonance Spectroscopy; D050997:Nanomedicine; D053758:Nanoparticles; D012516:Osteosarcoma / Q000188:drug therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D015202:Protein Engineering; D017550:Spectroscopy, Fourier Transform Infrared
D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D008024:Ligands; D008055:Lipids; D011100:Polyglycolic Acid; D017886:Durapatite; D002118:Calcium; D019386:Alendronate