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Published on: February 9, 2019
Folic Acid-Modified Long-Circulating Liposomes Loaded with Sulfasalazine For Targeted Induction of Ferroptosis in
Dong Zhang1, Mogen Zhang1, Yunyan Pang1
1Department of Dermatology, Affiliated Hospital of Weifang Medical University, Weifang 261031, China.
Abstract:
Melanoma is a malignant tumor that originates from melanocytes. The incidence of melanoma is increasing worldwide, partially because of its insensitivity to radiotherapy or chemotherapy. Therefore, effective treatments for melanoma are urgently required. In this study, we employed folic acid-modified sulfasalazine long-circulating liposomes (FA-SSZ-Lips) to precisely target drug delivery to melanoma cells, eliciting ferroptosis effectively. The synthesized FA-SSZ-Lips were characterized as small spheres of a double-layer membrane, a particle size of 110.1 nm, and a ζ-potential of -22.8 ± 0.66 mV. FA-SSZ-Lips are effective drug carriers with SSZ-loading ratio and SSZ release rate of 6.2 ± 0.10%, and 72.63 ± 1.40%, respectively. The liposomes enhanced SSZ solubility, and the folic acid modifications increased the liposome targeting to melanoma cells. Compared with SSZ alone, FA-SSZ-Lips more strongly inhibited B16F10 cell growth, significantly disrupted the intracellular redox balance, and induced ferroptosis. After treatment, considerable differences were observed in the tumor volumes between FA-SSZ-Lips and phosphate-buffered saline control groups. The tumor growth-inhibition value of the FA-SSZ-Lips group reached 70.09%. Thus, FA-SSZ-Lips exhibited favorable antitumor effects in vitro and in vivo and are a promising strategy for melanoma treatment.
Insights
Folic acid-modified sulfasalazine liposomes (FA-SSZ-Lips) effectively target melanoma cells, inducing cell death via ferroptosis. This novel drug delivery system shows significant promise for melanoma treatment by inhibiting tumor growth.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Melanoma incidence is rising globally, with limited treatment options due to resistance to conventional therapies.
- Developing targeted drug delivery systems is crucial for effective melanoma treatment.
- Ferroptosis, a form of regulated cell death, presents a potential therapeutic vulnerability in melanoma.
Purpose of the Study:
- To develop and evaluate folic acid-modified sulfasalazine long-circulating liposomes (FA-SSZ-Lips) for targeted melanoma therapy.
- To investigate the efficacy of FA-SSZ-Lips in inducing ferroptosis and inhibiting melanoma cell growth.
- To assess the in vitro and in vivo antitumor effects of FA-SSZ-Lips.
Main Methods:
- Synthesis and characterization of FA-SSZ-Lips, including particle size and zeta potential.
- Evaluation of drug loading capacity and release rate of sulfasalazine (SSZ).
- In vitro studies using B16F10 melanoma cells to assess cytotoxicity, redox balance disruption, and ferroptosis induction.
- In vivo studies to evaluate tumor volume reduction and antitumor efficacy in a melanoma mouse model.
Main Results:
- FA-SSZ-Lips were successfully synthesized as stable nanoparticles with optimal size and surface charge.
- The liposomes demonstrated enhanced SSZ solubility and targeted delivery to melanoma cells via folic acid modification.
- FA-SSZ-Lips significantly inhibited B16F10 cell proliferation, disrupted redox balance, and induced ferroptosis.
- In vivo studies showed a significant reduction in tumor volume, with a tumor growth inhibition of 70.09% in the FA-SSZ-Lips group.
Conclusions:
- FA-SSZ-Lips represent a promising targeted drug delivery system for melanoma.
- The developed liposomes effectively induce ferroptosis and exhibit significant antitumor activity in vitro and in vivo.
- FA-SSZ-Lips offer a novel and effective therapeutic strategy for combating melanoma.
