HomeDiseaseGA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma

GA&HA-Modified Liposomes for Co-Delivery of Aprepitant and Curcumin to Inhibit Drug-Resistance and Metastasis of Hepatocellular Carcinoma

August 20, 2022

Int J Nanomedicine. 2022 Jun 7;17:2559-2575. doi: 10.2147/IJN.S366180. eCollection 2022.

ABSTRACT

BACKGROUND: Tumor microenvironment (TME) plays a vital role in the development of hepatocellular carcinoma (HCC). Mounting evidence indicates that peripheral nerves could induce a shift from quiescent hepatic stellate cells (HSCs) to cancer-associated fibroblasts (CAFs) by secreting substance P (SP). The anti-tumor strategy by targeting “SP-HSCs-HCC” axis might be an effective therapy to inhibit tumor growth and metastasis.

OBJECTIVE: In this study, we prepared novel liposomes (CUR-APR/HA&GA-LPs) modified with hyaluronic acid (HA) and glycyrrhetinic acid (GA) for co-delivery aprepitant (APR) and curcumin (CUR), in which APR was chosen to inhibit the activation of HSCs by blocking SP/neurokinin-1 receptor (NK-1R), and CUR was used to induce apoptosis of tumor cells.

RESULTS: To mimic the TME, we established “SP+HSCs+HCC” co-cultured cell model in vitro. The results showed that CUR-APR/HA&GA-LPs could be taken up by CAFs and HCC simultaneously, and inhibit tumor cell migration. Meanwhile, the “SP+m-HSCs+HCC” co-implanted mice model was established to evaluate the anti-tumor effect in vivo. The results showed that CUR-APR/HA&GA-LPs could inhibit tumor proliferation and metastasis, and reduce extracellular matrix (ECM) deposition and tumor angiogenesis, indicating a superior anti-HCC effect.

CONCLUSION: Overall, the combination therapy based on HA&GA-LPs could be a potential nano-sized formulation for anti-HCC therapy.

PMID:35698562 | PMC:PMC9188407 | DOI:10.2147/IJN.S366180

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.