Anti-HIF-1alpha antibody-conjugated pluronic triblock copolymers encapsulated with Paclitaxel for tumor targeting therapy

Abstract

Targeted uptake of nanoscale controlled release polymer micelles encapsulated with drugs represents a potential powerful therapeutic technology. Herein we reported the development of anti-HIF-1alpha antibody-conjugated unimolecular polymer nano micelles filled with Paclitaxel for cancer targeting therapy. Pluronic triblock copolymers(Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PEO-block-PPO-block-PEO) P123 were functionalized with terminal carboxylic groups, and were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and differential scanning calorimetric (DSC). The amphiphilic copolymer nano micelles encapsulated with Paclitaxel were fabricated by self-assembly means, and then were conjugated with anti-HIF-1alpha antibody, the resultant anti-HIF-1alpha conjugated nano micelles filled with PTX (anti-HIF-1alpha-NMs-PTX nanocomposites) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells, these treated cells were analyzed by MTT and cell-ELISA. The nanocomposites composed of anti-HIF-1alpha conjugated nano micelles filled with CdTe quantum dots were also prepared, and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells for 24 h, then were observed by fluorescent microscope. Results showed that the anti-HIF-1alpha-NMs-PTX nanocomposites were successfully prepared, bound with stomach cancer MGC-803 cells specifically, were internalized, and released PTX inside cancer cells, and selectively killed cancer cells. In conclusion, unique anti-HIF-1alpha antibody-conjugated nano micelles filled with Paclitaxel can target and selectively kill cancer cells with over-expression of HIF-1alpha, and has great potential in clinical tumor targeting imaging and therapy.