Hyaluronic acid-modified doxorubicin PAMAM nanoparticles to overcome cancer multi-drug resistance / 中国药学杂志

ABSTRACT

OBJECTIVE: Chemotherapy is the primary treatment in addition to surgery and radiotherapy in cancer therapy, and drug resistance of tumor cells remains a major obstacle to successful cancer chemotherapy. In present study, we aim to develop a novel drug delivery system, ie, doxorubicin (DOX) conjugated poly (amido amine) (PAMAM) dendrimers was further decorated by hyaluronic acid (HA) (DOX-PAMAM-HA) to circumvent drug resistance in cancer cells. METHODS: Nuclear magnetic resonance (NMR) was performed to confirm the synthesis of the DOX-PAMAM-HA, its average size was analyzed by a dynamic light-scattering detector, and its morphological examination was performed by transmission electron microscope (TEM). To study the ability of DOXPAMAM-HA in overcome multi-drug resistance, the multi-drug resistant breast cancer cells (MCF-7/ADR cells) was used as model cell, and the confocal microscopy was utilized to observe the drug intracellular distribution, moreover, the hematoxylin-eosin staining (HE) studies were employed to evaluate the tissue staining and toxicity. RESULTS: The drug delivery system DOX-PAMAM-HA was successfully synthesized, which is spherical particles with a average particle size of 323 nm. The uptake in MCF-7/ADR cells for DOXPAMAM-HA is higher than that of DOX solution, and DOX-PAMAM-HA maybe distribute mainly in the lysosome of the cells, which could increase the accumulation of DOX in its action target (nucleus). In contrast, DOX solution was mainly diffused in the cytoplasm of the tumor cells. Furthermore, less toxicity in heart and spleen induced by DOX-PAMAM-HA in comparing to that of DOX solution after intravenous administration for 3 weeks. CONCLUSION: DOX-PAMAM-HA is a prospect future nanodrug delivery system in overcoming drug-resistance of tumor cells.