Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78

Abstract

Nanoparticles (NPs) which target specific agents could effectively recognize the target cells and increase the stability of chemical agents by encapsulation. As such, NPs have been widely used in cancer treatment research. Recently, over 90% of treatment failure cases in patients with metastatic cancer were attributed to resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa (GRP78) is expressed highly on many tumor cell surfaces in many human cancers and is related to the regulation of invasion and metastasis. Herein, we report that NPs conjugated with antibody against GRP78 (mAb GRP78-NPs) inhibit the adhesion, invasion, and metastasis of hepatocellular carcinoma (HCC) and promote drug delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug accumulation by effectively transporting NPs into cell surface GRP78-overexpressed human hepatocellular carcinoma cells and then inhibit cell proliferation and viability and induce cell apoptosis by regulating caspase-3. In brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery.

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

“…For example, Wang et al demonstrated that ursolic acid NP inhibited cervical cancer migration through inducing apoptosis 21 . BSA-based GRP78 receptor-targeting NP have been shown to inhibit hepatocellular carcinoma (HCC) cell invasion via receptor-mediated binding 20 . While local metastasis is the hallmark and the root cause of the high brain cancer mortality, there has not been any attempt so far as published in public domain to study the effect of NP uptake on invasion.…”

“…4). There were existing studies describing the inhibition of invasion by using NP loaded with radioisotopes and chemotherapeutics on hepatocellular carcinoma and gastric cancer 20,63 , in which the cell invasions were inhibited by the cytotoxicity of the payload. In this study, pSiNP was not carrying any therapeutics, and the treatment did not hamper viability nor intracellular ATP content (Fig.…”

“…A range of nanoparticles (NP) have been developed to deliver small molecular drugs to inhibit cancer cell migration [17][18][19] . Interestingly, a few studies reported that NP treatments alone are inhibitory to cancer cell invasion of liver 20 , cervical 21 , and breast 22 origins. However, studies on the potential of NP treatments in attenuating GBM invasion and migration are absent, despite the hallmark of GBM being their infiltrative phenotype.…”

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

“…153 155,156 GRP78 mAb-conjugated bovine serum albumin (BSA) loaded with 5-FU was developed to promote 5-FU into HCC cells and inhibit the adhesion, invasion, and metastasis of HCC, 157 which was verified by cell administrations. The AF-20 mAb has a high affinity for AF-20 antigen, which was found to distribute uniformly on 15/15 HCC tissues tested but was not evident on adjacent normal liver or in most normal human tissues.…”

Caracterización del efecto de ISM1 sobre células Leucémicas Humanas

“…Aunque la función fisiológica de GRP78 en la superficie celular dista de ser totalmente comprendida, se ha obtenido evidencia de que GRP78 puede formar complejos con proteínas específicas en la membrana plasmática desencadenando señales involucradas en procesos oncogénicos como son: sobrevivencia, proliferación, invasión, metástasis y quimioresistencia (Zhao et al, 2015, Tsai et al, 2015. La unión de la forma activa de la proteína inhibidora de proteasas a 2 Macroblobulina a GRP78 en la membrana plasmática en la línea celular de cáncer de próstata 1-LN desencadena la proliferación y supervivencia de las células cancerosas a través de la activación de la vía PI3K/AKT , NF-kB y UPR (Misra et al, 2006).…”