Glucosamine conjugated poly-galacturonic acid nanoparticles for targeted delivery of dacarbazine in melanoma: An in vitro/in vivo study

Abstract

Melanoma is a malignant tumor that originates from melanocytes, the cells responsible for producing skin pigment. It represents a significant public health challenge due to its increasing incidence and ability to metastasize. This study aimed to develop targeted nanoparticles (NPs) for the delivery of dacarbazine (DTIC) to tumor cells, thereby enhancing the drug's cytotoxic effects. DTIC was incorporated into calcium chloride (CaCl2) cross-linked poly-galacturonic acid NPs. To improve targeting to glucose receptors on tumor cells, glucosamine (GlcN) was conjugated to poly-galacturonic acid (PGalA). After optimizing the polymer/drug ratio, the cytotoxicity of the formulation was assessed in vitro on B16F10 cells (which are receptor positive) and L929 cells (which are receptor negative) using the MTT assay. Cellular uptake of both targeted and non-targeted NPs was evaluated using a fluorescent microscope. The anticancer efficacy of the cross-linked GlcN-PGalA/DTIC formulation was tested in mice with melanoma tumor induced by B16F10 cells. The optimized targeted NPs demonstrated a particle size of 243.56 nm, a zeta potential of-11.50 mV, and a polydispersity index of 0.322, with a satisfactory encapsulation efficiency of 62.6. Drug release efficiency was monitored over 12 h, revealing that approximately 83 of the drug was released from the cross-linked GlcN-PGalA/DTIC NPs after 6 h. The cytotoxicity and cellular uptake of GlcN-PGalA/DTIC were significantly higher than those of the free drug, while the PGalA/DTIC treatment led to a notable reduction in tumor volume. The GlcN-PGalA-/DTIC group achieved the highest tumor inhibition rate (TIR) of approximately 87.81. whereas the free DTIC group and non-targeted NPs (PGalA-DTIC) showed TIR values of 22.87 and 29.71, respectively. Therefore, cross-linked GlcN-PGalA/DTIC NPs represent a promising targeted delivery system for melanoma treatment.