Engineered Nanomedicine with Alendronic Acid Corona Improves Targeting to Osteosarcoma

Abstract

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.

Synthesis and characterization of a tumor-seeking LyP-1 peptide integrated lipid–polymer composite nanoparticle

“…The appearance of the broad and strong signal between 3169 and 3334 cm À1 is attributed to the formation of an amide bond between the carboxylic group and the primary amine group from the LyP-1 peptide after conjugation (spectrum in red, bottom panel). 42,46 It is notable that after the conjugation, the shifting of the carbonyl CQO peak from 1730 to 1647 cm À1 (highlighted with the black dotted line) with clear distinction absorption bands at 1647 cm À1 and at 1566 cm À1 , and the N-H out of plane wagging at 729 to 675 cm À1 (highlighted with the black dotted arrow) confirm the successful peptide conjugation (Fig. 1).…”

“…1). 42,48 The presence of peptide on the surface of the nanoparticles is characterized using a calorimetric rapid gold BCA assay according to the manufacturer's protocol (ESI-2, ESI †).…”

“…A timedependent MTT assay was conducted as discussed in the literature. [41][42][43][44] In a typical in vitro experiment, the cells were cultured in DMEM containing 10% (v/v) fetal bovine serum and 1% (w/v) penicillin-streptomycin at 37 1C in 5% CO 2 and 95% air. Non-cancerous and cancerous cells were used in this study and maintained according to the manufacturer's recommendations.…”

“…DOX loading was quantified spectrophotometrically at excitation and emission wavelengths of 490 nm and 580 nm following the published protocol. 38,42 The results showed that the initial DOX loading can be precisely tuned by varying the drug input (10,25,50,100,150,200, 300, and 400 mg mg À1 of PLGA weight) during the NP preparation process. Among the different initial DOX feeding concentrations, the maximum encapsulation efficiency of the control NP was found to be about 93% ( Fig.…”

Interaction of Immune System Protein with PEGylated and Un-PEGylated Polymeric Nanoparticles

“…Unmodified poly (D, L-lactide-co-glycolide) (PLGA-COOH) and modified (PLGA-PEG-NH2) NPs were prepared in Dr. Aryal's Lab by nanoprecipitation technique as reported elsewhere [15] [35] [36]. In brief, 1 mg of PLGA-COOH in 100 µL acetonitrile was added dropwise into 1mL Milli-Q water under magnetic stirring.…”