Improved anti-hepatocellular carcinoma effect by enhanced Co-delivery of Tim-3 siRNA and sorafenib via multiple pH triggered drug-eluting nanoparticles

Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy

“…The inhibition of ICP receptors such as LAG-3 and PD-1 on T cells was investigated in this study in order to increase the efficiency of T cells in response to DC vaccines [ 52 ]. T cell immunoglobulin mucin-3 (Tim-3) is a newly discovered immune checkpoint molecule and a promising target for HCC treatment [ 14 , 128 ]. Song et al developed a novel pH-triggered drug-eluting NP (CC@SR&SF@PP) for simultaneous administration of Tim-3 siRNA and sorafenib to HCC in vivo.…”

“…Following pH-triggered sorafenib release from SF@PP NPs, tumor proliferation and angiogenesis were significantly inhibited, resulting in remarkable tumor growth suppression in a mouse hepatoma 22 orthotopic tumor model. As a result, the co-delivery of Tim-3 siRNA and sorafenib via this unique pH-triggered drug-eluting NP improves the anti-tumor effect [ 128 ]. We anticipate that these combination treatment methods will have tremendous promise in future clinical uses.…”

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy

“…Hence, nanostructures are promising candidates for sustained delivery of drugs in HCC therapy [94] . pH-sensitive nanostructures can be employed for co-delivery of sorafenib and Tim3-siRNA to provide gene-/chemo-therapy [95] . Increased blood circulation time and promoted retention at tumor tissue are other benefits of using nanoparticles in HCC therapy [96] .…”

Lipid Nanovesicle Platforms for Hepatocellular Carcinoma Precision Medicine Therapeutics: Progress and Perspectives

“… 47 They delivered nanovesicles containing siRNA to Yes-associated protein 1 (YAP), a key downstream transcriptional co-activator of Hippo signaling, resulting in tumor regression through directing hepatocyte differentiation to normal hepatocyte-like cells. Other groups have also delivered nanoliposomes containing siRNAs targeting PD-L1, 48 T cell immunoglobulin mucin-3 49 (Tim-3; immune checkpoint molecule), vascular endothelial growth factor 50 (VEGF; angiogenic factor), alpha-fetoprotein 51 (AFP; biomarker for HCC), cyclo-oxygenase-2 52 (COX-2; important for prostaglandin synthesis in inflammatory processes), hypoxia inducible factor 1 subunit alpha 53 (HIF1a), or RNA N 6 − methyladenosine (m 6 A) reader protein YTHDF1 54 either alone or in combination with chemotherapeutics. Moreover, miRNAs can be packaged into nanoliposomes to target specific cellular pathways.…”