In:
Nanoscale Advances, Royal Society of Chemistry (RSC), Vol. 6, No. 12 ( 2024), p. 3135-3145
Kurzfassung:
The interplay between vascularization and macrophage-induced immune suppression plays a crucial role in melanoma treatment. In this study, we propose a novel combination approach to combat melanoma by simultaneously inhibiting tumor vascularization and enhancing macrophage-mediated anti-tumor responses. We investigate the potential of combining combretastatin A4 (CA4), a vascular-disrupting agent, with poly(I:C) (PIC), an immunostimulatory adjuvant. This combination approach effectively suppresses melanoma cell proliferation, disrupts vascularization, and promotes macrophage polarization towards the M1 phenotype for melanoma suppression. To facilitate efficient co-delivery of CA4 and PIC for enhanced anti-angiogenic immunotherapy, we develop an injectable metal–organic framework hydrogel using Zeolitic Imidazolate Framework-8 (ZIF-8) and hyaluronic acid (HA) (ZIF-8/HA). Our findings demonstrate that ZIF-8 enables efficient loading of CA4 and enhances the stability of PIC against RNAase degradation in vitro . Furthermore, the developed co-delivery hydrogel system, PIC/CA4@ZIF-8/HA, exhibits improved rheological properties, good injectability and prolonged drug retention. Importantly, in vivo experiments demonstrate that the PIC/CA4@ZIF-8/HA formulation significantly reduces the dosage and administration frequency while achieving a more pronounced therapeutic effect. It effectively inhibits melanoma growth by suppressing angiogenesis, destroying blood vessels, promoting M1 macrophage infiltration, and demonstrating excellent biocompatibility. In conclusion, our study advances anti-angiogenic immunotherapy for melanoma through the potent combination of PIC/CA4, particularly when administered using the PIC/CA4@ZIF-8/HA formulation. These findings provide a new perspective on clinical anti-angiogenic immunotherapy for melanoma, emphasizing the importance of targeting tumor vascularization and macrophage-mediated immune suppression simultaneously.
Materialart:
Online-Ressource
ISSN:
2516-0230
Sprache:
Englisch
Verlag:
Royal Society of Chemistry (RSC)
Publikationsdatum:
2024
ZDB Id:
2942874-9
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