[Construction and Anti-tumor Effect Evaluation of a Dual-Responsive Hyaluronic Acid Carbon Quantum Dot-Gelatin Nano-Drug Delivery System].

OBJECTIVE: To construct a pH and matrix metalloproteinase (MMP) dual-responsive nano drug delivery system with adjustable particle size so as to synergistically enhance the retention and penetration of chemotherapeutic drugs in tumor tissues and improve tumor treatment effect. METHODS: Hyaluronic acid (HA) carbon quantum dots (CD) coupled with gelatin nanoparticle (GNP) were constructed, and were connected with doxorubicin (DOX), a chemotherapeutic drug, through pH-sensitive imine to produce GNP@HA-CD-DOX nanoparticles. The changes of particle size, drug release behavior, hemocompatibility, cell uptake and deep penetration of tumor spheroids, in vivo tumor targeting and therapeutic effect were analyzed. RESULTS: GNP@HA-CD-DOX nanoparticles had a particle size of (162.93±2.55) nm, which could be degraded to release HA-CD-DOX with a particle size of about 40 nm under the treatment of MMP. The drug loading of DOX was (4.94±0.22)%. DOX was released in the tumor microenvironment and lysosomes in response to the low pH. No obvious hemolysis was observed in GNP@HA-CD-DOX. GNP@HA-CD-DOX showed a reduction in particle size after co-incubation with MMP-2. The MMP-sensitive GNP@HA-CD-DOX had significantly improved cell uptake and better deep penetration in tumor spheres. GNP@HA-CD-DOX displayed better distribution in tumor and anti-tumor ability in tumor-bearing mice compared with the small particle size HA-CD-DOX group. In addition, it has better safety. CONCLUSION: The pH and MMP dual-sensitive nano-tech drug delivery system with adjustable particle sizes synergistically enhances the retention and deep penetration of drugs in tumors as well as the anti-tumor effect, suggesting new approaches to tumor treatment.

Mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation for ferroptosis after spinal cord injury.

Spinal cord injury is characterized by different aetiologies, complex pathogenesis, and diverse pathological changes. Current treatments are not ideal, and prognosis is generally poor. After spinal cord injury, neurons die due to various forms of cell death. Among them, ferroptosis causes dysfunction after spinal cord injury, and no existing traditional treatments have been indicated to block its occurrence. Meanwhile, emerging therapies using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation therapy are promising for reversing spinal cord neuronal ferroptosis after spinal cord injury. However, no definitive studies have demonstrated the effectiveness of these approaches. This review summarizes the existing research on the mechanisms of ferroptosis; ferroptosis after spinal cord injury; treatment of spinal cord injury with mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation; and treatment of ferroptosis using mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation. Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury. In addition, mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation can reverse adverse outcomes of spinal cord injury and regulate ferroptosis-related factors. Thus, it can be inferred that mesenchymal stem cells, extracellular vesicles, and transcranial magnetic stimulation have the potential to inhibit ferroptosis after spinal cord injury. This review serves as a reference for future research to confirm these conclusions.