Pericyte-targeting drug delivery and tissue engineering - PubMed (original) (raw)

Review

. 2016 May 27:11:2397-406.

doi: 10.2147/IJN.S105274. eCollection 2016.

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Review

Pericyte-targeting drug delivery and tissue engineering

Eunah Kang et al. Int J Nanomedicine. 2016.

Abstract

Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes.

Keywords: angiogenesis; pericyte-targeting drug delivery; pericytes; platelet-derived growth factor; tissue engineering; vascular remodeling.

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Figures

Figure 1

Figure 1

Graphical illustration of pericytes’ recruitment and their potential targeting delivery. Notes: Pericytes are regressed or activated depending on the up- and downregulation of VEGF and PDGF-β mainly. Targeting tools of pericytes are diverse as a form of peptides, small chemical molecules, DNA, and antibody, exploiting overexpressed marker on the pericyte cellular membrane or blocking the pathway of PDGFR-β+ under tumor microenvironment. Abbreviations: PDGF-β, platelet-derived growth factor β; PDGFR-β+, platelet-derived growth factor receptor β-positive; VEGF, vascular endothelial growth factor.

Figure 2

Figure 2

Pericyte tissue engineering with suspended ECs. Notes: (A) The process of pericyte cell encapsulation. (B) Pericytes encapsulated in an alginate microgel reservoir. (C) The communication between suspended ECs and pericytes within alginate microgel by paracrine cellular signals makes the rearrangement of suspended ECs possible, reconstructing three-dimensional remodeling. Reprinted from Biomaterials, 34, Andrejecsk JW, Cui J, Chang WG, Devalliere J, Pober JS, Saltzman WM, Paracrine exchanges of molecular signals between alginate-encapsulated pericytes and freely suspended endothelial cells within a 3D protein gel, 8899–8908, Copyright (2013), with permission from Elsevier. Abbreviation: ECs, endothelial cells.

Figure 3

Figure 3

The design of pericyte-targeting delivery carriers. Notes: (A) Lipid vesicles conjugated to pericyte-targeting peptide motifs; CPRECES to target membrane-APA and TAASGVRSMH (TH10) to target NG2 proteoglycan on pericyte cell membrane. (B) Protein carriers conjugated to a pericyte-targeting cyclic peptide, CSRNLIDC, to block PDGFR-β under pericyte-developed tumor environment. Abbreviations: APA, aminopeptidase A; NG2, neural/glial antigen 2; PDGFR-β, platelet-derived growth factor receptor β; DOX, doxorubicin.

Figure 4

Figure 4

Pericyte-targeting small molecules that act at blockade of the PDGFR-β+ pericytes. Notes: (A) 6 as chemical analog synthesized as tyrosine kinase inhibitor, (B) sorafenib as tyrosine kinase inhibitor, (C) imatinib as tyrosine kinase inhibitor, and (D) valproic acid as histone deacetylase inhibitor. Abbreviation: PDGFR-β+, platelet-derived growth factor receptor β-positive.

References

    1. Cheng L, Huang Z, Zhou W, et al. Glioblastoma stem cells generate vascular pericytes to support vessel function and tumor growth. Cell. 2013;153:139–152. -PMC -PubMed
    1. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–523. -PubMed
    1. Guichet PO, Guelfi S, Teigell M, et al. Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells. Stem Cells. 2015;33:21–34. -PubMed
    1. Sims DE. The pericyte – a review. Tissue Cell. 1986;18:153–174. -PubMed
    1. Sims DE. Diversity within pericytes. Clin Exp Pharmacol Physiol. 2000;27:842–846. -PubMed

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