Abstract
BackgroundCell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells.MethodsUsing in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate–labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice.ResultsIn each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups.ConclusionCPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor.
Highlights
Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability
Comparing the mean fluorescence intensities and positive rates of three colorectal cancer (CRC) cell lines, we concluded that CPP2 a higher Mean fluorescence intensity (MFI) and positive rate than both R8 and TAT (p < 0.05)
We explored the anti-tumor function of the synthetic peptides in CRC cells by comparison with minimal inhibitory sequence of p16 (p16MIS) and CPP2
Summary
Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. This process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells. Because of the specialty of noninvasive and negligibly cytotoxic transport through macropinocytosis and/or endocytosis, they were named cell-penetrating peptides (CPPs) [1, 2]. Wang et al BMC Cancer (2016) 16:571 non-neoplastic cells restricted the in vivo application of the CPPs identified to date [15]. CPP cell specificity is especially important for cancer therapy to minimize side effects on normal cells [16]. To gain insight into the targeting ability of CPP2 in CRC, HCT116, SW480, and HL-7702 cells were used for comparison with LoVo cells in the in vitro experiments
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