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. 2023 Mar 31;15(7):1753.
doi: 10.3390/polym15071753.

Nucleus-Targeting Nanoplatform Based on Dendritic Peptide for Precise Photothermal Therapy

Wen-Song Wang  1 , Xiao-Yu Ma  1 , Si-Yao Zheng  1 , Si Chen  1 , Jin-Xuan Fan  2 , Fan Liu  1 , Guo-Ping Yan  1
Affiliations

Nucleus-Targeting Nanoplatform Based on Dendritic Peptide for Precise Photothermal Therapy

Wen-Song Wang et al. Polymers (Basel). .

Abstract

Photothermal therapy directly acting on the nucleus is a potential anti-tumor treatment with higher killing efficiency. However, in practical applications, it is often difficult to achieve precise nuclear photothermal therapy because agents are difficult to accurately anchor to the nucleus. Therefore, it is urgent to develop a nanoheater that can accurately locate the nucleus. Here, we designed an amphiphilic arginine-rich dendritic peptide (RDP) with the sequence CRRK(RRCG(Fmoc))2, and prepared a nucleus-targeting nanoplatform RDP/I by encapsulating the photothermal agent IR780 in RDP for precise photothermal therapy of the tumor nucleus. The hydrophobic group Fmoc of the dendritic peptide provides strong hydrophobic force to firmly encapsulate IR780, which improves the solubility and stability of IR780. Moreover, the arginine-rich structure facilitates cellular uptake of RDP/I and endows it with the ability to quickly anchor to the nucleus. The nucleus-targeting nanoplatform RDP/I showed efficient nuclear enrichment ability and a significant tumor inhibition effect.

Keywords: arginine-rich dendritic peptide; nuclear localization; precise photothermal therapy; tumor inhibition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Structural formula of RDP; (B) The synthesis diagram of RDP/I; (C) Schematic diagram of the nanoheater RDP/I for precise nucleus-targeting photothermal therapy, (I) Nanoheater RDP/I was internalized in cells. (II) RDP/I escaped from the endosome. (III) RDP/I was anchored to the nucleus. (IV) Cell death due to the precise nuclear photothermal effect of RDP/I.
Figure 2
Figure 2
(A) The CMC of RDP; (B) UV-vis absorption spectra of RDP/I and IR780; (C) particle size and TEM image of RDP/I; (D) release behavior of RDP/I; (E) temperature changes of samples (IR780 concentration was 30 μg/mL) with NIR irradiation (808 nm, 1 W); (F) cyclic stability test of samples (IR780 concentration was 30 μg/mL) with NIR irradiation (808 nm, 1 W).
Figure 3
Figure 3
(A) Photothermal images and (B) the heating curve of RDP/I at different concentrations with NIR irradiation (1 W); (C) photothermal images and (D) the heating curve of RDP/I (IR780 concentration was 30 μg/mL) with NIR irradiation at different laser powers.
Figure 4
Figure 4
In vitro anti-tumor performance of samples. Cytotoxicity of samples against (A) CT26 cancer cells and (B) NIH3T3 normal cells; data are shown as mean ± SD (n = 4); (C) fluorescent images of sample treated CT26 cells stained with Calcein AM; (D) wound healing assay of sample treated CT26 cells; the scale bar: 50 μm.
Figure 5
Figure 5
(A) CLSM images of CT26 cells after being treated with samples for 4 h; scale bar: 20 μm; (B,C) quantitative analysis of intracellular fluorescence intensity in CT26 cells after being treated with samples for 4 h.
Figure 6
Figure 6
(A,B) Quantitative measurement of apoptosis by AnnexinV-FITC/PI in CT26 cells after treated with samples in the absent or present of NIR irradiation (808 nm, 1 W, 1 min); (C) growth inhibition of CT26 cells spheroids after treated with samples in the absent or present of NIR irradiation (808 nm, 1 W, 1 min); scale bar: 100 μm.
See this image and copyright information in PMC

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