Hybrid Hydrogel Composed of Carboxymethylcellulose–Silver Nanoparticles–Doxorubicin for Anticancer and Antibacterial Therapies against Melanoma Skin Cancer Cells

Abstract

Malignant melanoma is the utmost severe form of skin cancer, causing the vast majority of deaths related to skin cancer in humans. Although melanoma is treatable at its early stages at localized forms, metastatic melanoma remains a therapeutic challenge with dramatically increased incidence in the past few years. In addition, opportunistic pathogens can provoke infections leading to ulceration of cutaneous melanoma. Herein, we designed and synthesized hybrid hydrogels made of silver nanoparticles (AgNPs) embedded in the carboxymethyl­cellulose (CMC) polymer cross-linked networks conjugated with doxorubicin (DOX), the anticancer drug. This system was synthesized by a green process, using a single-pot in situ reduction of Ag+ by CMC polymer, which also acted as capping ligand, followed by the electrostatic conjugation with DOX, forming colloidal nanocomplexes in aqueous media. These nanoconjugates were chemically cross-linked with citric acid (CA) under mild pH and temperature conditions. The results demonstrated the effective nucleation and stabilization of spherical AgNPs nanocolloids, with uniform size distribution (d ∼ 10 nm). The physicochemical properties of the hybrid nanocomplexes (AgNP@CMC-DOX) were affected by the degree of carboxymethylation (DS = 0.8 and 1.2) of CMC related to the development of supramolecular nanocolloidal dispersions. These nanohybrids were predominantly stabilized by electrostatic interactions between carboxylate groups (anionic, CMC) and amino groups (cationic, DOX), forming vesicle-like nanosystems. These AgNP@CMC-DOX nanostructures were cross-linked producing hybrid hydrogels (AgNP@CMC-DOX-CA), with gel fraction and swelling degree properties dependent on the DS. Consequently, these hybrids demonstrated tuned DOX intracellular kinetics in vitro, evidencing a synergistic effect with AgNPs for killing melanoma cancer cells. Moreover, these hybrid nanocomposites proved antimicrobial activity against Gram-positive and Gram-negative bacterias. Thus, an innovative platform was designed and developed based on nanoparticle–polysaccharide–drug nanostructures for producing anticancer and antibacterial hybrid hydrogels to be applied as a weapon in the arsenal against skin cancer via topical drug delivery chemotherapy.

Sunlight-Induced Synthesis of Non-Target Biosafety Silver Nanoparticles for the Control of Rice Bacterial Diseases

“…Compared with silver ions, the antibacterial activity of CMC-SNs prepared by the method reported in this paper is slightly lower, which is consistent with similar results reported in the literature. However, it has been reported that the silver nanoparticles coated with polysaccharide have the characteristic of slow release [ 25 ], which may be more suitable for the control of rice bacterial diseases.…”

Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering

“…In addition, hybrid system also showed good antimicrobial potentials against different Gram-positive and Gram-negative bacteria. Thus, an innovative hybrid hydrogels platform was produced with anticancer and antibacterial properties and could be successfully applied as a weapon against skin cancer (Capanema et al, 2019 ).…”

Recent Advances in Nanotechnology for the Treatment of Melanoma

“…Capanema and collaborators designed and synthesized hybrid hydrogels made of silver nanoparticles (AgNPs) embedded a carboxymethylcellulose (CMC)-based hydrogel conjugated with doxorubicin (DOX), an anticancer drug [ 60 ]. This system was synthesized by a green process, using an in situ reduction of Ag+ by CMC polymer, which also acted as capping ligand, followed by the electrostatic conjugation with DOX, with the formation of colloidal nanocomplexes in aqueous media.…”