Study on the optical and biological properties in vitro of IR808-PEG-FA.

IR808, an IR780 derivative, is capable of fluorescently imaging and photodynamic therapy in vitro and in vivo. However, its application is greatly hampered by hydrophobicity, toxicity and nonspecific delivery to the targeting tissue and that causes accumulation in the liver and kidney. In order to overcome these limitations, we prepared IR808-PEG-FA from IR808, amino-terminated poly(ethylene glycol) (NH2 -PEG-NH2 , denoted as PEG) and folate (FA). PEG, an accepted hydrophilic medicinal agent, was introduced to improve hydrophobicity, and FA was used to increase targeting ability of the conjugate. The obtained product provides a good water solubility and stronger light intensity in near infrared (NIR)-imaging, and CCK-8 test demonstrated which had no appreciable toxicity. In addition, the cell uptake results indicated that IR808-PEG-FA was specifically targeted to positive tumors cells with folate receptor (FR) compared with IR808, and thus it may be used as a novel diagnostic agent or imaging-guided agent for cancer treatment. So this article provides a way to improve hydrophobicity, optical stability and targeting ability in the field of nano-probe for fluorochromes.

PLA-PEG-FA NPs for drug delivery system: Evaluation of carrier micro-structure, degradation and size-cell proliferation relationship.

In this paper, the micro-structure of amphiphilic copolymer Polylactic acid-Polyethylene glycol-Folate (PLA-PEG-FA) was studied firstly by a differential scanning calorimetry (DSC). During the process of nanoparticles (NPs) preparation, we found good inter-structure consistency of polymer was the precondition for forming into stable NPs, and those with micro-phase separation structure were prepared of NPs within limits. Hemolytic test and CCK-8 assay results demonstrated the biotoxicity of both NPs and whose leaching liquor was far below related toxicity standards. Two kinds of cell, human breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (EC), showed different manners in test of NPs size-cell proliferation relationship, respectively. Monitored by a nuclear magnetic resonance (NMR) and a gel permeation chromatography (GPC), the degradation behavior of NPs in aqueous solution indicated amide bond break more difficultly than ester bond, and FA classic proton peak disappeared in the third week, meanwhile lactic acid (LA) unit number became 25% of the initial. Finally the NPs was completely degraded in the eighth week. In the whole process, NPs underwent a change from compact to loose state. We hope these results will benefit to improve design of drug delivery system in nanomedicine, which could offer the selection rule for amphiphilic polymer NPs on material and size.

Dodecanol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA) nanoparticles: evaluation of cell cytotoxicity and selecting capability in vitro.

Folate-conjugated Dol-poly(D,L-lactic acid)-b-poly (ethylene glycol)-folate (Dol-PLA-PEG-FA), was synthesized from dodecanol-poly(D,L-lactic acid), amino-terminated poly(ethylene glycol) and folate. (1)H NMR proved the successful synthesis of Dol-PLA-PEG-FA. Nanoparticles (NPs) were further fabricated from Dol-PLA-PEG-FA by using solvent evaporation-induced interfacial self-assembly method. The size, critical micelle concentration (CMC), cytotoxicity and selecting capability to cancer cells in vitro were examined for Dol-PLA-PEG-FA NPs. The size of NPs showed polymer concentration-dependent phenomenon in the fabrication process, and its polydispersity index (PDI) was very narrow. The CMC was determined as 1.995×10(-4) g/L in aqueous solution, which is much lower than the reported CMC of block copolymer self-assemble micelles. The cytotoxicity evaluation revealed that the obtained NPs2 are non-toxic to either breast cancer cell or normal endothelial cells, and the cell uptake of NPs indicated that the NPs demonstrated much higher selecting capability to breast cancer cells compared to normal fibroblast cells. The possible receptor-mediated endocytosis pathway mechanism was proposed. Based on the above results, it could be concluded that Dol-PLA-PEG-FA polymer and its nanoparticles can be potentially used as a safe drug carrier with strong tumor cells targeting capability for tumor chemotherapy.