To overcome this problem, we constructed three versions of peptide (Pep12)-modified nano-hybrids by replacing the GNP core with different cores that were made of clinically applicable materials in this study (Figure 1a): M-P12, Lipo-P12, and PLGA-P12. We anticipated that these new cores may also bring additional functionality to the nano-hybrids. M-P12 was made of self-assembled distearoyl-phosphatidylethanolamine-poly(ethylene glycol) (2000)-maleimide (DSPE-PEG2000-MAL) nanomicelles (M-MAL) that were conjugated with Pep12 (CLPFFD) on the surface by Michael addition reaction between the maleimide of the DSPE-PEG2000-MAL and the thiol group of the cysteine (C) residue at the N-terminal of Pep12 (Figure 1b). The nuclear magnetic resonance hydrogen spectroscopy (1H NMR) was applied to confirm the conjugation of Pep12 on the nanomicelle surface. The disappearance of the maleimide peak (at 6.7 ppm) in DSPE-PEG2000-MAL and the appearance of the benzene peak of the peptide (at 7.1–7.2 ppm) in DSPE-PEG2000-Pep12 suggested the complete conjugation of Pep12 to the nanomicelle (Figure S1a, Supporting Information). Lipo-P12 was fabricated by inserting DSPE-PEG2000-Pep12 into the phospholipid bilayer of the DSPE liposomes (Lipo). PLGA-P12 was constructed by conjugating Pep12 to PLGA monomers via amide bond formation (Figure 1b), followed by nano-precipitation to form peptide-modified PLGA nanoparticles. The appearance of the benzene peak in the NMR spectra of PLGA-P12 suggested the successful conjugation of Pep12 to PLGA (Figure S2a, Supporting Information).

我們構(gòu)建了三種版本的肽（Pep12）修飾的納米雜化物，通過(guò)用本研究中臨床適用材料制成的不同核替換GNP核：M-P12、Lipo-P12和PLGA-P12。

我們預(yù)計(jì)這些新內(nèi)核也可能為納米混合動(dòng)力車帶來(lái)額外的功能。M-P12由自組裝的二硬脂酰磷脂酰乙醇胺聚乙二醇（2000）-馬來(lái)酰亞胺（DSPE-PEG2000-MAL）納米膠束（M-MAL）制成，通過(guò)DSPE-PEG2000/MAL的馬來(lái)酰亞胺與Pep12 N端半胱氨酸（C）殘基的巰基之間的邁克爾加成反應(yīng)，在表面與Pep12（CLPFD）偶聯(lián)。核磁共振氫譜（1H NMR）用于確認(rèn)Pep12在納米膠束表面上的共軛。

DSPE-PEG2000-MAL中馬來(lái)酰亞胺峰（6.7 ppm）的消失和DSPE-PEG2000/Pep12中肽的苯峰（7.1-7.2 ppm）的出現(xiàn)表明Pep12與納米膠束完全結(jié)合。

Lipo-P12是通過(guò)將DSPE-PEG2000-Pep12插入DSPE脂質(zhì)體（Lipo）的磷脂雙層中制備的。PLGA-P12是通過(guò)酰胺鍵形成將Pep12偶聯(lián)到PLGA單體上構(gòu)建的，然后進(jìn)行納米沉淀形成肽修飾的PLGA納米顆粒。PLGA-P12的NMR光譜中苯峰的出現(xiàn)表明Pep12與PLGA成功結(jié)合。

相關(guān)推薦：

DLPE-PEG-SC

DLPE-ICG

Palmitic acid-PEG-SC

DSPE-PEG-TRITC

RB-PEG-DSPE，DSPE-PEG-RB

ICG-PEG-DLPE

ICG-PEG-DMPE

ICG-PEG-DOPE

ICG-PEG-DPPE

ICG-PEG-DSPE

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