Co-Delivery of angiostatin and curcumin by a biodegradable polymersome for antiangiogenic therapy

Author(s): Yue Cao ¹ ^, ² ^, ³ ^, ⁴ , Yan Li ⁵ ^, ² ^, ⁶ ^, ⁴ , Yin Wu ⁵ ^, ² ^, ⁶ ^, ⁴ , Wenliang Li ⁵ ^, ² ^, ⁶ ^, ⁴ , Chunlei Yu ⁵ ^, ² ^, ⁶ ^, ⁴ , Yanxin Huang ⁷ ^, ² ^, ⁶ ^, ⁴ , Luguo Sun ⁷ ^, ² ^, ⁶ ^, ⁴ , Yongli Bao ⁵ ^, ² ^, ⁶ ^, ⁴ , Yuxin Li ¹ ^, ² ^, ³ ^, ⁴

Publication date (Electronic): 2016

Journal: RSC Advances

Publisher: Royal Society of Chemistry (RSC)

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Abstract

Illustration of the AS–Cur-loaded polymersomes formed by block polymers for antiangiogenic therapy.

Abstract

Co-Encapsulated angiostatin (AS) and curcumin (Cur) in poly(ethylene glycol)- b-poly(ε-caprolactone) polymersomes (PEG–PCL-PMs) were prepared by film hydration method. The size and zeta potential of the prepared PEG–PCL-PMs were about 153 nm and −0.22 mV, respectively. Transmission electron microscopy was employed to confirm the polymersomal structure of PEG–PCL-PMs. In vitro drug release profiles showed a sustained release of angiostatin and curcumin from the dual-drug loaded polymersomes under physiological conditions (pH 7.4). In addition, confocal laser scanning microscopy and flow cytometry showed that drug-loaded polymersomes were delivered efficiently into the cytoplasm and nuclei of human microvascular endothelial cell line (HMEC-1) and then released active drugs in cells. Dual drug-loaded polymersomes (AS–Cur-PMs) remarkably inhibited proliferation and migration of HMEC-1 cells compared to those treated with the single drug. The chick chorioallantoic membrane assay showed that AS–Cur-PMs inhibited vessel sprouting in the chicken chorioallantoic membrane. Our data demonstrates a synergistic effect of angiostatin and curcumin in inhibiting angiogenesis, both in vitro and in vivo.

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Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma.

M O'Reilly, L Holmgren, Y Shing … (1994)

The phenomenon of inhibition of tumor growth by tumor mass has been repeatedly studied, but without elucidation of a satisfactory mechanism. In our animal model, a primary tumor inhibits its remote metastases. After tumor removal, metastases neovascularize and grow. When the primary tumor is present, metastatic growth is suppressed by a circulating angiogenesis inhibitor. Serum and urine from tumor-bearing mice, but not from controls, specifically inhibit endothelial cell proliferation. The activity copurifies with a 38 kDa plasminogen fragment that we have sequenced and named angiostatin. A corresponding fragment of human plasminogen has similar activity. Systemic administration of angiostatin, but not intact plasminogen, potently blocks neovascularization and growth of metastases. We here show that the inhibition of metastases by a primary mouse tumor is mediated, at least in part, by angiostatin.

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Polymersomes for drug delivery: design, formation and characterization.

Jung Lee, Jan Feijen (2012)

In the last past dozen years, polymersomes (Ps) have attracted tremendous attention as versatile carriers because of their colloidal stability, tunable membrane properties and ability in encapsulating or integrating a broad range of drugs and molecules. Relatively long blood circulation times of Ps can be accomplished when block copolymers with a poly(ethylene glycol) (PEG) are used for the formation of Ps. A number of Ps has been developed for new possibilities and applications in drug delivery, medical imaging, electronics and nanoreactors. In particular, Ps prepared by using biodegradable and/or stimuli-sensitive block copolymers that are responsive to various internal or external stimuli are of great interest for such applications. In this review, recent advances of Ps as drug delivery systems are discussed. Critical factors that influence the formation of Ps are also addressed. The review describes preparative methods and characterization techniques for Ps. Moreover, protein and cell interactions with Ps, in vivo circulation kinetics and biodistribution of Ps are addressed.