MMP inhibitor(Paratek Pharmaceuticals)

Melanoma, a malignancy characterized by high aggressiveness and fatality, is often treated by reactivating the immune system using immune checkpoint inhibitors. Research indicates that inhibition of matrix metalloproteinases (MMPs) can effectively block immune checkpoints. However, the current MMP inhibitor, rutin (RUT), lacks efficient delivery mechanisms to target the tumor microenvironment (TME). Therefore, this study aimed to develop pH-responsive micelles for targeted and accurate delivery into the TME, overcoming the limitations of RUT itself. RUT-carboxyphenylboronic acid (CPBA) was synthesized by coupling the boronic acid group of CPBA with the catechol group of RUT using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and N-Hydroxysuccinimide (NHS) as coupling agents, which was then esterified with Astragalus polysaccharide (ASP) to obtain ASP-CPBA-RUT (ACR) micelles. The ACR micelles demonstrate the ability to selectively release ASP and RUT within the acidic extracellular TME (pH = 6.8). Compared to RUT, the ACR micelles had a significantly enhanced antimelanoma effect, with a melanoma suppressive effect of 67.25% (1.49 times that of RUT), a larger area of melanoma cell necrosis, and a longer life cycle in tumor-bearing mice. Through the modulation of the CD8⁺T/Treg and CD4⁺T/Treg ratios within the TME, as well as the reduction of MDSC and MDSCs cell infiltration and the enhancement of interferon-γ (IFN-γ) secretion, the ACR micelles achieved a synergistic regulation of the TME by ASP and RUT while enhancing the effectiveness of PD-L1 immunotherapy. In conclusion, ACR micelles demonstrate TME-stimulated responsive drug release capabilities and can reverse the immunosuppressive TME while enhancing the effectiveness of PD-L1 immune checkpoint therapy. This innovative drug delivery system not only presents a promising strategy for immunotherapy in melanoma treatment, but also introduces a novel method for delivering active components of traditional Chinese medicine to the TME.

Matrix metalloproteinases (MMPs) degrade the hybrid layer in dentin bonding, affecting composite restoration longevity. Inhibitors like tetracyclines, chlorhexidine (CHX), and ethylenediaminetetraacetic acid (EDTA) can enhance bond strength. In vitro studies compare these inhibitors' effects on shear bond strength (SBS), aiming to improve clinical outcomes and extend restoration lifespan.

This study aims to compare the effects of different MMP inhibitors on the SBS between composite and dentin using a universal testing machine.

A total of 64 freshly extracted human premolars, free from cracks or defects, were collected, disinfected in 0.5% chloramine T solution, and stored in distilled water for use within 6 months. These premolars, exhibiting normal anatomy and from patients without orthodontic treatment history, were divided into four groups, including a control group. Teeth were meticulously cleaned, embedded in acrylic resin blocks, and underwent prophylaxis with pumice and water. Composite cylinder build-ups were performed on the specimens, and their SBS was measured.

SBS among four different MMP inhibitors, with and without thermocycling, shows a significant difference (p = 0.003 and p < 0.001, respectively). Without thermocycling, the control group (10.97 MPa) shows the highest SBS, while 17% EDTA (5.32 MPa) showed the lowest. Similarly, with thermocycling, 2% CHX (10.97 MPa) exhibited the highest SBS, and 17% EDTA (3.92 MPa) showed the lowest.

CHX emerged as the most effective MMP inhibitor, with 2% chlorhexidine showing the highest SBS in both thermocycling and nonthermocycling groups, while 17% EDTA showed the lowest. MMP inhibitors, particularly 2% chlorhexidine, help maintain improved dentin bonding durability of adhesive restorations after thermocycling.

Honaje NV, Ninawe N, Anija CK, et al. Comparative Evaluation of the Effect of Different Matrix Metalloproteinase Inhibitors on Shear Bond Strength between Composite and Dentin: An In Vitro Study. Int J Clin Pediatr Dent 2025;18(9):1066-1070.