Supplementary figure 1 Scheme showing the synthesis of GALA/PEG2000 Cys-GALA was conjugated with DSG-PEG2000-MAL (the molar ratio of 1:1) via Micheal reaction between the maleimide moiety of DSG-PEG2000-MAL and the thiol group of cysteine from Cys-GALA. The reaction was conducted in ethanol at 30ºC, 24 hours.

Supplementary figure 2 MALDI-TOF/MS spectra of Cys-GALA (a), DSG-PEG2000-MAL (b) and GALA/PEG2000 (c)

Supplementary figure 3: In vivo confocal observation of GALA-modified liposomes in lung at 6 hours DiI-labeled liposomes were modified with 2 mole% GALA/Chol or GALA/PEG2000 to form GALA/Chol-LPs and GALA/PEG2000-LPs, respectively. The liposomes were intravenously administered at 26.4 nmol lipid/g body weight. At 6 hours post-administration, the mice were sacrificed, and lungs were collected to make fresh slices. The slices were stained with Fluorescein Griffonia (Bandeiraea) Simplicifolia Lectin I-isolectin B4 for endothelial staining. Traces of the liposome were observed via Nikon-A1 confocal laser microscopy. Supplementary figure 3a represents a non-treated lung, whereas the lungs treated with PEG-LPs, GALA/Chol-LPs and GALA/PEG2000-LPs are shown in Supplementary Figure 3b, 3c and 3d, respectively.

Supplementary figure 3: In vivo confocal observation of GALA-modified liposomes in lung at 6 hours DiI-labeled liposomes were modified with 2 mole% GALA/Chol or GALA/PEG2000 to form GALA/Chol-LPs and GALA/PEG2000-LPs, respectively. The liposomes were intravenously administered at 26.4 nmol lipid/g body weight. At 6 hours post-administration, the mice were sacrificed, and lungs were collected to make fresh slices. The slices were stained with Fluorescein Griffonia (Bandeiraea) Simplicifolia Lectin I-isolectin B4 for endothelial staining. Traces of the liposome were observed via Nikon-A1 confocal laser microscopy. Supplementary figure 3a represents a non-treated lung, whereas the lungs treated with PEG-LPs, GALA/Chol-LPs and GALA/PEG2000-LPs are shown in Supplementary Figure 3b, 3c and 3d, respectively.

Supplementary figure 3: In vivo confocal observation of GALA-modified liposomes in lung at 6 hours DiI-labeled liposomes were modified with 2 mole% GALA/Chol or GALA/PEG2000 to form GALA/Chol-LPs and GALA/PEG2000-LPs, respectively. The liposomes were intravenously administered at 26.4 nmol lipid/g body weight. At 6 hours post-administration, the mice were sacrificed, and lungs were collected to make fresh slices. The slices were stained with Fluorescein Griffonia (Bandeiraea) Simplicifolia Lectin I-isolectin B4 for endothelial staining. Traces of the liposome were observed via Nikon-A1 confocal laser microscopy. Supplementary figure 3a represents a non-treated lung, whereas the lungs treated with PEG-LPs, GALA/Chol-LPs and GALA/PEG2000-LPs are shown in Supplementary Figure 3b, 3c and 3d, respectively.

Supplementary figure 3: In vivo confocal observation of GALA-modified liposomes in lung at 6 hours DiI-labeled liposomes were modified with 2 mole% GALA/Chol or GALA/PEG2000 to form GALA/Chol-LPs and GALA/PEG2000-LPs, respectively. The liposomes were intravenously administered at 26.4 nmol lipid/g body weight. At 6 hours post-administration, the mice were sacrificed, and lungs were collected to make fresh slices. The slices were stained with Fluorescein Griffonia (Bandeiraea) Simplicifolia Lectin I-isolectin B4 for endothelial staining. Traces of the liposome were observed via Nikon-A1 confocal laser microscopy. Supplementary figure 3a represents a non-treated lung, whereas the lungs treated with PEG-LPs, GALA/Chol-LPs and GALA/PEG2000-LPs are shown in Supplementary Figure 3b, 3c and 3d, respectively.

Supplementary Figure 4 Specificity of siRNA sequences on CD31 gene silencing in lung by GALA/PEG2000-MEND C57BL/6N mice (6-week, male) were injected with the GALA/PEG2000-MEND encapsulating siRNA at a dose of 0.5 mg siRNA/kg. Specificity of siRNA sequences were evaluated between GALA/MEND encapsulating with anti-CD31 siRNA and anti-GL4 siRNA. At 24 hours after injection, CD31 mRNA expression in the lung was assessed by qRT-PCR. Data are shown as mean ± SD (n=5). The statistical difference was determined by One-way ANOVA with Bonferroni test. ** p < 0.01

Supplementary Figure 5 Dose-response curve of CD31 knockdown activity in liver C57BL/6N mice (6-week, male) were injected with MENDssPalmE (solid line) or GALA/PEG2000-MENDssPalmE (modified with 2 mole% GALA/PEG2000; dashed line) at doses of 0.01-0.5 mg siRNA/kg. At 24 hours after injection, CD31 mRNA levels in the lung were determined by TaqMan real-time PCR. mRNA expression was also determined as internal control. Relative expression of CD31/CD34 mRNA levels was shown as mean ± SD (n = 5-6).