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

Matthewos Eshete,Tuyen Duong Thanh Nguyen,Seong-O Choi,Kayla Bailey,Santosh Aryal

doi:10.4236/anp.2017.63009

Matthewos Eshete, Tuyen Duong Thanh Nguyen + Show 3 more

Open Access

https://doi.org/10.4236/anp.2017.63009

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Abstract

Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.

Highlights

Particles with the size ranging from 1 nm to 100 nm are called nanoparticles (NPs)
We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein
This study explored the binding of modified and unmodified biodegradable NPs (PLGA-COOH and PLGA-PEG-NH2) with Recombinant Human MannoseBinding Protein C (HMBP) in an effort to understand the effect of surface modification of the NPs on protein binding

Summary

Introduction

Particles with the size ranging from 1 nm to 100 nm are called nanoparticles (NPs). They possess enhanced or altered physical, chemical and biological properties which make them superior in different applications than the corresponding bulk counterparts [1]-[9]. We hypothesized that collectin proteins could recognize and bind to specific structural features of NPs as they bind to their target molecules on the surface of microorganisms This could be one of the mechanisms that trigger various immunological responses of NPs. This study explored the binding of modified and unmodified biodegradable NPs (PLGA-COOH and PLGA-PEG-NH2) with Recombinant Human MannoseBinding Protein C (HMBP) in an effort to understand the effect of surface modification of the NPs on protein binding. Recombinant Human Mannose-Binding Protein C/MBL-2 (HMBP) was diluted to create various concentrations in the calcium-containing blocking/binding buffer (1% w/v BSA in TBS) and added to the wells to give a final volume of 100 μL/well and incubated for 2 h with blocking/binding buffer at room temperature to allow binding. The UV absorbance of each well was scanned in the wavelength range of 300 nm to 500 nm

Findings

Result and Discussion

Conclusion