Abstract
As a natural compound, gambogic acid (GA) emerged a shining multi-target antitumor activity in a variety of tumors. Whereas its poor solubility and non-specific effect to tumor blocked the clinical application of this drug. Herein, we reported a simple and effective strategy to construct liposome modified with nuclear targeted peptide CB5005N (VQRKRQKLMPC) via polyethylene glycol (PEG) linker to decrease the inherent limitations of GA and promote its anti-tumor activity. In this study, liposomes were prepared by thin film hydration method. The characterization of formulations contained particle size, Zeta potential, morphology and encapsulation efficiency. Further, in vitro cytotoxicity and uptake tests were investigated by 4T1 and MDA-MB-231 cells, and nuclear targeting capability was performed on MDA-MB-231 cells. In addition, the in vivo antitumor effect and biological distribution of formulations were tested in BALB/c female mice. The GA-loaded liposome modified by CB5005N showed small size, good uniformity, better targeting, higher anti-tumor efficiency, better tumor inhibition rate and lower toxicity to normal tissues than other groups. In vitro and in vivo research proved that CB5005N-GA-liposome exhibited excellent anti-tumor activity and significantly reduced toxicities. As a result, CB5005N-GA-liposome nano drug delivery system enhanced the tumor targeting and antitumor effects of GA, which provided a basis for its clinical application.
Highlights
Breast cancer is the second leading reason of cancer death closely followed lung cancer in females and males (Bray et al, 2018; Gu and Li, 2020; Juan et al, 2020)
It has been found that a range of monomers of traditional Chinese medicine with anti-tumor activity, such as gambogic acid, neogambogic acid, curcumin, matrine and so on (Cheng et al, 2020; Hatami et al, 2020; Zha et al, 2020; D’Angelo et al, 2021), compared with single-target chemical drugs, the anti-tumor active components of traditional Chinese medicine provide a new idea for tumor prevention and treatment through the synergistic regulation of multi-targets and multi-pathways
MDA-MB-231 cells were cultured in RPMI1640 medium containing 15% Fetal bovine serum (FBS), and 4T1 cells were cultivated in Dulbecco’s modified Eagle’s medium (DMEM) medium added to 10% FBS, these cells were cultivated in a humidified atmosphere containing 5% CO2 at 37°C
Summary
Breast cancer is the second leading reason of cancer death closely followed lung cancer in females and males (Bray et al, 2018; Gu and Li, 2020; Juan et al, 2020). GA, the most abundant ingredient of Gamboge, is a xanthone structure extracted from the dry brownish gamboge resin secreted from the Garcinia hanburyi tree in Southeast Asia, and has inherent anti-cancer properties, which exhibits remarkable programmed cell death, cell cycle arrest, anti-angiogenesis and antiinflammatory effects (Kashyap et al, 2016; Pandey et al, 2016). Because of these reasons, the anti-tumor effect had attracted widespread attention, GA could inhibit various cancer cell’s growth, including colorectal cancer, breast cancer, liver cancer, lung cancer, etc. The new drug delivery system based on nanotechnology could usefully encapsulate GA to overcome the poor water solubility and enhance the therapeutic effects in cancer therapy
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