Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles

Abstract

The engineering of drug-encapsulated targeted nanoparticles (NPs) has the potential to revolutionize drug therapy. A major challenge for the smooth translation of targeted NPs to the clinic has been developing methods for the prediction and optimization of the NP surface composition, especially when targeting ligands (TL) of different chemical properties are involved in the NP self-assembly process. Here we investigated the self-assembly and properties of two different targeted NPs decorated with two widely used TLs that have different water solubilities, and developed methods to characterize and optimize NP surface composition. We synthesized two different biofunctional polymers composed of poly(lactide-co-glycolide)-b-polyethyleneglycol-RGD (PLGA-PEG-RGD, high water solubility TL) and PLGA-PEG-Folate (low water solubility TL). Targeted NPs with different ligand densities were prepared by mixing TL-conjugated polymers with non-conjugated PLGA-PEG at different ratios through nanoprecipitation. The NP surface composition was quantified and the results revealed two distinct nanoparticle assembly behaviors: for the case of PLGA-PEG-RGD, nearly all RGD molecules conjugated to the polymer were found to be on the surface of the NPs. In contrast, only ~20% of the folate from PLGA-PEG-Folate was present on the NP surface while the rest remained presumably buried in the PLGA NP core due to hydrophobic interactions of PLGA and folate. Finally, in vitro phagocytosis and cell targeting of NPs was investigated, from which a window of NP formulations exhibiting minimum uptake by macrophages and maximum uptake by targeted cells was determined. These results underscore the impact the ligand chemical properties have on the targeting capabilities of self-assembled targeted nanoparticles and provide an engineering strategy for improving their targeting specificity.

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells

“…26,27 In short, 10 mg of genistein and 100 mg of PCL polymer or TPGS-b-PCL copolymer were dissolved in 8 mL of acetone. Then the dissolved mixture was slowly added into 100 mL of 0.03% (w/v) TPGS aqueous solution using a 1 mL injector, under stirring.…”

“…As described previously, 26,27 genistein-loaded PCL and TPGS-b-PCL NPs were prepared by a modified nanoprecipitation method using acetone as the solvent and TPGS as the emulsifier. Then the NPs were characterized in detail.…”

The antitumor activity of a doxorubicin loaded, iRGD-modified sterically-stabilized liposome on B16-F10 melanoma cells: in vitro and in vivo evaluation

“…[1][2][3] Ligand-modified targeting drug delivery systems can bind with specific tumor surfaces' overexpressing receptors to increase the drug concentration at the tumor site and significantly improve therapeutic efficacy. 4,5 For example, Arg-Gly-Asp (RGD) -or Asn-Gly-Arg (NGR)-modified targeting drug delivery systems have been extensively investigated.…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…[571] Additionally, a careful consideration is needed to maximize the binding quality on nanoparticles due to hydrophobic nature of FA ligands. [572] Other vitamins such as biotin (vitamin H), which is a cell growth promoter, [573] have been also conjugated on silica, liposome, iron oxides, and polymer based nanoparticles with avidin (strept) functionalities on their surfaces for targeting cancers, oral delivery of insulin and in vitro applications. [574] However, clinical applications of biotins are somehow limited due their bacterial origin and consequent immunogenicity.…”