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47 Gambogic acid delivery using lipid nanoparticles modified with cell-penetrating peptide
  1. Mingzhi Zhao1,
  2. Jingying Li1,
  3. LuoMin Xiao1,
  4. Jie Zeng1,
  5. DanChun Zhang1,
  6. Robert J Lee2,3,
  7. Lesheng Teng1,2
  1. 1Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai, China
  2. 2School of Life Sciences, Jilin University, Changchun, China
  3. 3Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA


Objectives Gambogic acid (GA) is a novel tissue-specific proteasome inhibitor which can potentially be used to treat cancer with low toxicity. However, poor aqueous solubility (∼10 μg/mL) and low tumor cell-specific delivery have limited its clinical application. Clinical application of GA requires the development of delivery vehicles.

Methods In this study, we developed a novel nanoparticle GA delivery system. The nanoparticles incorporate a cell-penetrating peptide conjugated to myristic acid (MA-R7W), a folate modified lipid (FA-PEG2000-DSPE), a pH-sensitive lipid (PEG1000-hyd-PE), eggPC and cholesterol. The lipids formed the nanoparticle shells, and GA was loaded into the lipid bilayer of the nanoparticles. PEG on the surface of the nanoparticles provides a long circulation time. Folate is incorporated to enable targeting of tumor cells with amplified folate receptor expression. PEG1000-hyd-PE can shield/unshield R7W on the nanoparticle surface according to the pH difference between normal tissues and cancer.

Results In vitro, FA/MA-R7W nanoparticles improved cellular uptake 2.5-fold compared to GA liposomes (without FA-PEG2000-DSPE, AA-R8 and PEG1000-hyd-PE) at pH 5. In vivo, GA encapsulated in FA/MA-R7W nanoparticles induced potent tumor inhibition (62.6%), showed lengthy circulation (Figure 1) and tumor cell targeting.

Abstract 47 Figure 1

Plasma concentration-time curves in rats for FA/MA-R7W nanoparticles and free gambogic acid (1 mg/kg)

Conclusions In conclusion, FA/MA-R7W nanoparticles are promising vehicles for GA delivery and warrant further investigation.

Acknowledgments This research was financially supported by Jilin Province Science and Technology Development Program (Grant No. 20140311072YY) and Jilin Province Science and Technology Development Program (Grant No.20150520141JH).

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