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Surface modification of polymeric nanoparticles with human adipose derived stem cell membranes AdMSCs

Jagathesh Chandra Bose Rajendiran1, 2*, Kim Byoung-Ju2, Soo Hong Lee2 and Hansoo Park1*
  • 1 Chung- Ang University, School of Integrative Engineering, Korea
  • 2 CHA University, Department of Biomedical sciences, Korea

Introduction: The clinical efficacy of systemic nanomedicine delivery depends on their ability to escape from immune system, cross the biological barriers and sufficient localization at desired tissue[1]. Human Adipose derived mesenchymal stem cells (hAdMSCs) have all of these properties and exert their targeting function through various receptors on cellular membrane that interact with specific ligands[2]. These characteristic features of hAdMSCs can be applied to enhance the performance of nanomedicine by biomimetic surface modification. The purpose of the study was to develop a novel biomimetic functionalization of polymeric nanoparticles using hAdMSCs.

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Methods and Materials: Physio-chemical characterizations were performed to confirm the morphology, size, and stability of stem cell membrane coated particles (SHNPs) using transmission electron microscopy, confocal microscopy and dynamic light scattering. Western blotting, flow cytometry, and immuno fluorescence assay were used to verify cell surface markers and protein content. In vitro transwell and phagocytic assay were performed to investigate the ability to translocate across the endothelial cells and inhibit immune cells uptake. Furthermore, we investigated the pharmacokinetic and bio distribution of SHNPs by incorporating fluorophore-loaded SHNPs.

Results and Discussion: The experiment results showed that SHNPs had nano size range (100-150 nm) with narrow polydispersity index (PDI) 0.17 and core-shell hybrid structures.

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Flow cytometry, immunofluorescence analysis, and western blotting confirmed the presence of stem cell marker on SHNPs. In addition, in vitro assay results further confirmed that the hybrid structure of SHNPs was able to avoid rapid clearance of phagocytic cells uptake and successfully translocate across reconstructed endothelium. Moreover, in vivo animal study showed that stem cell biomimetic functionalization significantly enhanced the circulation time of SHNPs as compared with bare particles.

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Conclusion: Herein we have demonstrated stem cell membrane functionalization significantly enhanced the blood circulation time, sufficiently inhibited immune cells uptake and crossed the endothelial barriers. We postulated that these SHNPs have a great promise as a systematic target specific nano carrier system for multiple bioactive molecules delivery, such as small-molecule drugs and genes/RNA for the treatment of various diseases.

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI14C3484)

References:
[1] Parodi, Alessandro, et al. "Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions." Nature nanotechnology 8.1 (2013): 61-68.
[2] Naderi‐Meshkin, Hojjat, et al. "Injectable hydrogel delivery plus preconditioning of mesenchymal stem cells: exploitation of SDF‐1/CXCR4 axis towards enhancing the efficacy of stem cells' homing." Cell biology international (2015).

Keywords: stem cell, Biomimetic, nanoparticle, Surface modification

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Biomaterials in gene therapy

Citation: Rajendiran J, Byoung-Ju K, Lee S and Park H (2016). Surface modification of polymeric nanoparticles with human adipose derived stem cell membranes AdMSCs. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01711

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Received: 27 Mar 2016; Published Online: 30 Mar 2016.

* Correspondence:
Dr. Jagathesh Chandra Bose Rajendiran, Chung- Ang University, School of Integrative Engineering, Seoul, Korea, Email1
Dr. Hansoo Park, Chung- Ang University, School of Integrative Engineering, Seoul, Korea, heyshoo@cau.ac.kr