Alfa-hederin (Hed) is regarded as a promising drug in cancer therapy especially in drug-resistant cancers. However, its reduced anticancer activity caused by protein absorption limits its wide clinical applications. The purpose of this study was to develop diblock copolymer-based micelles as an integrated platform for targeted delivery of Hed to overcome its intrinsic drawbacks. Amphiphilic diblock copolymers, poly(epsilon-caprolactone)- b -poly(oligo(ethylene glycol) monomethyl ether methacrylate- co -RGD) (PCL- b -P(OEGMA- co -RGD)) consisting of hydrophobic PCL, hydrophilic POEGMA and targeting peptide (RGD) were fabricated via the combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and polymer post-functionalization. Hed-containing targeting micellar nanoparticles , Hed-NP-RGD, were obtained via the co-micellization of PCL- b -P(OEGMA- co -RGD) and Hed, showing hydrodynamic diameter 108 ± 1 nm and zeta potential −4.10 ± 0.15 mV. In vitro experiments demonstrated that Hed-NP-RGD possessed superior anti-proliferative and cellular apoptosis in comparison with that of free Hed possibly due to the assumption that the presence of polymeric micelles protected Hed molecules from absorption by proteins and tumor-targeting effect.
Gang Pan,Ting-ting Jia,Qian-xia Huang,Yan-yan Qiu,Jie Xu,Pei-hao Yin,Tao Liu
Novel methods to improve the anticancer performance of 5-fluorouracil (5-FU) is quite necessary for clinical medicines. In the present work, we fabricated a novel type of mesoporous silica nanoparticles (MSNs)-based inorganic/organic hybrid nanoparticles covalently attached with poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) for improved stabilization and targeting peptide (RGD) for targeted delivery with the aim of improving the anticancer performance of 5-FU. Atom transfer radical polymerization (ATRP) initiator functionalized MSN (MSN-Br) was synthesized at first, which was followed by surface-initiated ATRP of water soluble OEGMA and carboxyl-containing monomer (2-succinyloxyethyl methacrylate, SEMA). Functionalization of RGD onto the hydrophilic P(OEGMA- co -SEMA) chains afforded the final hybrid nanoparticle, MSN-P(OEGMA- co -RGD). 5-FU can be effectively loaded into the meso -pores of MSN-P(OEGMA-c o -RGD) ( [email protected] ) with drug content ∼7.5 wt%. And the dynamic diameter ( D h ) and zeta potential (ζ) of [email protected] were determined to be 199.3 ± 5.4 nm and −8.7 ± 0.5 mV, respectively. It was demonstrated that MSN-P(OEGMA-c o -RGD) exhibited improved internalization into colon cancer cells and enhanced accumulation in tumor tissues. In addition, compared with free 5-FU, [email protected] showed enhanced anticancer efficacy both in vitro and in vivo, implying promising clinical applications.
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