RGD-Conjugated Resveratrol HSA Nanoparticles as a Novel Delivery System in Ovarian Cancer Therapy

Figures & data

Table 1 Characterization of the Prepared RVT-HSA NPs

Formulation	Time (m)	Mean PS (nm)	PDI	ζ-Potential (mV)	RVT
					DL%	ER%
RVT-HSA NPs	0	118.3±9.77	0.143±0.051	−26.71±5.53	6.5±1.45	79.8±5.87
RGD-RVT-HSA NPs	0	128.2±11.56	0.132±0.045	−21.42±4.56	7.6±1.39	83.6±6.34
	1	125.6±12.71	0.136±0.072	−23.54±5.52	7.4±1.44	82.4±5.78
	3	123.8±12.89	0.138±0.082	−25.36±6.16	7.1±1.27	82.3±5.19

Figure 1 (A) The basic structure of RGD-RVT-HSA NPs. The transmission electron microscope of RGD-RVT-HSA NPs (B) and RVT-HSA NPs (C). (Magnification ×100,000).

Figure 2 Cumulative drug release (mean ± SD %, n = 6) profiles of free RVT, RVT-HSA NPs, RGD-RVT-HSA NPs and RGD-RVT-HSA NPs (3m) over time intervals of 2, 4, 8, 12, 24, 48, 72, 96, and 120 h.

Figure 3 Confocal images of cellular uptake of blank NPs (A), free RVT (B), RVT-HSA NPs (C), RGD-RVT-HSA NPs (D) by SKOV-3 cells. Incubation time was 2 hours. (E) Fluorescence intensity of four groups. ^ap < 0.05, compared with blank NPs; ^bp < 0.05, compared with free RVT; ^cp < 0.05, compared with RVT-HSA NPs.

Figure 4 Effect of different RVT formulations on cell death in SKOV3 cancer cells. Assessment of cell viability of SKOV3 cells treated with free RVT, RVT-HSA NPs and RGD-RVT-HSA NPs at RVT concentration of 0.5–75 µM for 15 min followed by 24 or 48 h incubations. ^ap < 0.05, compared with blank NPs; ^bp < 0.05, compared with free RVT; ^cp < 0.05, compared with RVT-HSA NPs.

Table 2 The AUC_0–12h of RVT in Plasma and Tissues After i.v. Administration of Injection and NPs to Mice (n=6)

Formulation	Tumor	Heart	Liver	Spleen	Lung	Kidney	Plasma
Free RVT (ng·h/g)	623.3*	669.8	1178.5	1506	901.3	1218.5	2482
RVT-HSA-NPs (ng·h/g)	1088.8*	839.8	1324	1304.8	1034.5	1400.5	1668.3
RGD-RVT-HSA NPs (ng·h/g)	4672.3	756	1194.8	1148	1112	1344	1520
Ratio^a	7.5	1.1	1.0	0.8	1.2	1.1	0.6
Ratio^b	4.3	0.9	0.9	0.9	1.1	1.0	0.9

Notes: ^aThe ratio was AUC (RGD-RVT-HSA NPs)/AUC (Free RVT); ^bThe ratio was AUC (RGD-RVT-HSA NPs)/AUC (RVT-HSA-NPs); *P<0.05: vs AUC (RGD-RVT-HSA NPs).

Figure 5 The research results of tissue distribution and in vivo imaging studies. (A) free RVT, (B) RVT-HSA NPs, (C) RGD-RVT-HSA NPs and (D) Fluorescence images of three groups (at 12 h).

Figure 6 Changes of tumor volume (A) and body weight (B) in nude mice transplanted with SKOV3 cancer cells of blank NPs, free RVT, RVT-HSA NPs and RGD-RVT-HSA NPs.