Dacarbazine-Loaded Targeted Polymeric Nanoparticles for Enhancing Malignant Melanoma Therapy

Abstract

Dacarbazine (DTIC) dominates chemotherapy for malignant melanoma (MM). However, the hydrophobicity, photosensitivity, instability, and toxicity to normal cells of DTIC limit its efficacy in treating MM. In the present study, we constructed star-shaped block polymers nanoparticles (NPs) based on Cholic acid -poly (lactide-co-glycolide)-b-polyethylene glycol (CA-PLGA-b-PEG) for DTIC encapsulation and MM targeted therapy. DTIC-loaded CA-PLGA-b-PEG NPs (DTIC-NPs) were employed to increase the drug loading and achieve control release of DTIC, followed by further modification with nucleic acid aptamer AS1411 (DTIC-NPs-Apt), which played an important role for active targeted therapy of MM. In vitro, DTIC-NPs-Apt showed good pH-responsive release and the strongest cytotoxicity to A875 cells compared with DTIC-NPs and free DTIC. In vivo results demonstrated that the versatile DTIC-NPs-Apt can actively target the site of MM and exhibited excellent anti-tumor effects with no obvious side effects. Overall, this research provided multi-functional NPs, which endow a new option for the treatment of MM.

Formulation, Characterization, Anti-Inflammatory and Cytotoxicity Study of Sesamol-Laden Nanosponges

“…B16F12 melanoma cells were seeded in a 96-well plate at a density of 20,000 cells/well and grown for 24 h. Thereafter, different concentrations of SES and SES-NS (10, 25, 50, 75, 100, and 200 µg/mL) were added and incubated for 48 h at a temperature of 37 °C in a CO 2 atmosphere (5%). Afterward, we added MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reagent to achieve a 0.5 mg/mL concentration and further incubated it for 3 h. Finally, the MTT reagent was removed, and we then added 100 μL of solubilization solution, and absorbance was measured at 630 nm with an ELISA reader [ 42 ]. The % cell viability was determined using the below formula: …”

Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma

“…Another source of materials of nanoparticles for darcarbazine is a common copolymer, cholic acid−poly-(lactide-co-glycolide)−b-polyethylene glycol (CA-PLGA-b-PEG). 197 In a study in 2022, Xiong et al synthesized those polymeric nanoparticles using "a modified nanoprecipitation method", which was facilitated by a mixture of acetone and methanol and an emulsifier of α-tocopheryl polyethylene glycol 1,000 succinate. The drug-encapsulated nanoparticles were finally purified using centrifuged and lyophilization.…”

“…The addition of amorphous silica to form AuSiO 2 creates a thick layer of core–shell conveniently encapsulating the drug. Another source of materials of nanoparticles for darcarbazine is a common copolymer, cholic acid–poly­(lactide- co -glycolide)– b -polyethylene glycol (CA-PLGA- b -PEG) . In a study in 2022, Xiong et al synthesized those polymeric nanoparticles using “a modified nanoprecipitation method”, which was facilitated by a mixture of acetone and methanol and an emulsifier of α-tocopheryl polyethylene glycol 1,000 succinate.…”

Nanoparticle-Based Combination Therapy for Melanoma

“…A new nanoformulation of paclitaxel-loaded cholic acid-functionalised star-shaped poly (lactide-co-glycolide) (PLGA)-d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) NPs (PTX-loaded CAPLGA-TPGS NPs) was produced by Yongsheng et al to treat malignant melanoma, and it showed a higher rate of release rate (78.69%), higher cellular uptake efficiency, and reduced growth of tumours in mice compared to those treated with saline (95). This year, DTIC (Dacarbazine)-NPs(Cholic acid -poly (lactide-co-glycolide)-b-polyethylene glycol)-Apt(nucleic acid aptamer AS1411) was developed to treat melanoma cell lines and showed good toxicity to MM but few side effects (96). The combination of NPs and chemotherapy have increased the EPR of the chemotherapy drug although different mechanisms.…”