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Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO₂; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO₂ nanoparticles.

ABSTRACT: Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO₂ nanocarrier. Then, an FA-PEG-TiO₂ nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation-solidification at low temperature. The obtained folate-targeted NPs (FA-NPs) showed more cytotoxicity on MCF7 cells and MDA-MB-231 cells than a nontargeted NP group. Apart from a synergistic anti-breast cancer effect with curcumin, salvianolic acid B protects the cardiovascular system from oxidative injury by the TiO₂ nanocarrier. With coumarin 6 as a fluorescent probe to observe cellular uptake of NPs, the results of in vitro cellular uptake demonstrated FA-NPs exhibited higher cellular uptake and accumulation in MCF7 cells and MDA-MB-231 cells than nontargeted NPs. Then, in vivo biodistribution of NPs was further qualitatively and quantitatively confirmed by in vivo imaging. More importantly, the animal study further suggested that FA-NPs had significantly stronger antitumor effects via receptor-mediated targeted delivery. Consequently, FA-PEG-TiO₂ NPs loaded with curcumin and salvianolic acid B could be a promising drug-delivery system to treat breast cancer.

SUBMITTER: Ding L

PROVIDER: S-EPMC5098748 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO2; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO2 nanoparticles.

Ding Lingling L Li Jiawei J Huang Rui R Liu Zhidong Z Li Chunhua C Yao Shaozi S Wang Jinyan J Qi Dongli D Li Nan N Pi Jiaxin J

International journal of nanomedicine 20161102

Targeted delivery by the folate ligand is an effective way to enhance an anti-breast carcinoma effect, due to its high affinity for the folate receptor, which is overexpressed in many tumor cells. In this study, we firstly synthesized a folic acid (FA)-targeted and polyethylene glycol (PEG)-modified TiO2 nanocarrier. Then, an FA-PEG-TiO2 nanoparticle (NP) codelivery system loaded with curcumin and salvianolic acid B were prepared by emulsion evaporation-solidification at lo ...[more]

PMID: 27843313

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Project description:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect. In the present study, we examined the utility of PEG5K-EB2 to deliver DOX to tumors. In addition, folic acid (FA) was coupled to the surface of the PEG5K-EB2 micelles (FA-PEG5K-EB2) to further improve the selective targetability of the system. DOX-loaded PEG5K-EB2 micelles were uniformly spherical particles with a diameter of approximately 20 nm. Incorporation of FA had minimal effect on the size of the particles. The DOX loading efficiency was as high as 91.7% and 93.5% for PEG5K-EB2 and FA-PEG5K-EB2, respectively. DOX formulated in PEG5K-EB2 micelles (with or without FA decoration) demonstrated sustained kinetics of DOX release compared to free DOX. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. P-gp ATPase assay showed that PEG5K-EB2 significantly inhibited the function of the P-gp efflux pump. The maximum tolerated dose of DOX-loaded PEG5K-EB2 micelles was 15 mg/kg in mice, which was 1.5-fold greater than that for free DOX. Pharmacokinetics (PK) and biodistribution studies showed that both types of DOX-loaded micelles, especially FA-PEG5K-EB2, were able to significantly prolong the blood circulation time of DOX and facilitate its preferential accumulation at the tumor tissue. Finally, DOX/PEG5K-EB2 mixed micelles demonstrated significantly enhanced tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil and the antitumor activity was further enhanced after the decoration by folic acid. Our data suggest that FA-PEG5K-EB2 micelles represent a promising DOX delivery system that warrants more study in the future.

Dataset Information

Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO₂; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO₂ nanoparticles.

Publications

Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO<sub>2</sub>; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO<sub>2</sub> nanoparticles.

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