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… sC-iRGD modified polymers exhibited excellent tumor targeting and tumor accumulation capacity compared to the FITC labeled PPA, and the tumor accumulation of polymers was confirmed by optical and fluorescence imaging. The hydrodynamic size and low-pH induced degradation of sC-iRGD was explored to address the potential of tumor triggered accumulation. A series of studies were carried out to analyze the potential application of PPA-FP-siRGD in the delivery of RNAi.

The PPA-FP-siRGD nanoparticle exhibited high loading efficiency for siRGD. In vitro release of siRGD was examined under different conditions. The release of siRGD was found to be pH-dependent. At acidic condition, sC-iRGD-PPAP was formed rapidly and released more siRGD when compared to the PPA-FP-siRGD formulation. The PPA-FP-siRGD NP showed excellent stability upon storage under different conditions. In vivo, the PPA-FP-siRGD NP possessed rapid degradation and released high level of siRGD in the tumor. The siRGD-PPA-FP NP was able to restrict tumor growth by reducing angiogenesis in comparison to the free siRGD. Besides, the siRNA loading capacity of PPA-FP-siRGD NP was up to 2.3 µg/µl, which was higher than that of the CPPs (1.6–2.8 µg/µl), and delivered siRNA with a higher transfection efficiency. The results are consistent with that of a recent study, which showed that an iRGD conjugation conferred a superior siRNA transfection efficiency and a reduced cytotoxicity when compared to LTX and FITC[@CIT0016] Furthermore, the safety evaluation of PPA-FP-siRGD NP was also performed. PPA-FP-siRGD NP caused minimal cytotoxicity at various concentrations of PPA-FP-siRGD NPs and PPA-FP-siRGD NPs at 72 h post-transfection. The in vivo toxicity was evaluated by intravenous injection of free Alexa-Fluor^®^ 488-siRGD NP in C57BL/6 mice. The no obvious histological changes or organ damage were observed in any of the organs, and no sign of serum toxicity was observed.
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