Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting “substance P-hepatic stellate cells-hepatocellular carcinoma” axis

Li, Zhipeng; Wang, Fangqing; Li, Yanying; Wang, Xiaoxue; Liao, Qiao; Wang, Di; Qi, Cuiping; Li, Chenglei; Li, Zhaohuan; Lian, Bo; Tian, Guixiang; Gao, Zhiqin; Zhang, Bo; Wu, Jingliang

doi:10.1016/j.biomaterials.2021.121003

Cited by 42 publications

(33 citation statements)

References 47 publications

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“…Our previous researches have proven that GA receptor and CD44 receptor were over-expressed on HCC cells and aHSCs, respectively. 11 , 44 The result might be due to the fact that HA&GA-LPs could be taken up by LX-2 and SMMC-7721 cells simultaneously, resulting in greater anti-HCC effects.…”

Section: Resultsmentioning

confidence: 99%

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

Li¹,

Wu²,

Qiao³

et al. 2022

IJN

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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.

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Section: Resultsmentioning

confidence: 99%

“… 9 , 10 Our previous researches have shown that SP could activate the hepatic stellate cells (HSCs) from quiescent phenotype to carcinoma-associated fibroblasts (CAFs), leading to drug resistance and metastasis of HCC. 11 Hence, blocking “SP-HSCs-HCC” axis might be a potential strategy to inhibit HCC development. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

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

Li¹,

Wu²,

Qiao³

et al. 2022

IJN

Self Cite

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“…The hepatic stellate cells (HSCs) activation can also induce EMT by secreting various messenger molecules, such as substance P (SP), and then promote the drug resistance of hepatocellular carcinoma (HCC). The therapy strategy based on capsaicin (CAP, an inhibition of SP) and DOX can inhibit the HSCs activation, inhibit the cancer metastasis, and suppress the HCC drug resistance (Li et al., 2021e ). Moreover, further decreasing oxygen (O 2 ) in cancer cells can create starvation effects for resensitizing chemotherapeutic drugs in MDR tumors.…”

Section: Disrupting Energy Metabolism or Signal Pathwaysmentioning

confidence: 99%

Recent advances in anti-multidrug resistance for nano-drug delivery system

Wang

Zhang

et al. 2022

Drug Delivery

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Chemotherapy for tumors occasionally results in drug resistance, which is the major reason for the treatment failure. Higher drug doses could improve the therapeutic effect, but higher toxicity limits the further treatment. For overcoming drug resistance, functional nano-drug delivery system (NDDS) has been explored to sensitize the anticancer drugs and decrease its side effects, which are applied in combating multidrug resistance (MDR) via a variety of mechanisms including bypassing drug efflux, controlling drug release, and disturbing metabolism. This review starts with a brief report on the major MDR causes. Furthermore, we searched the papers from NDDS and introduced the recent advances in sensitizing the chemotherapeutic drugs against MDR tumors. Finally, we concluded that the NDDS was based on several mechanisms, and we looked forward to the future in this field.

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“…An intelligent pH-sensitive DDS of CAPS/GA-sulfated HA (sHA) DOX-loaded NPs was developed for liver-targeting co-delivery of DOX and CAPS [ 64 ]. The potential role of CAPS against tumor growth has been described above [ 55 ].…”

Section: Environment-responsive Ga-functionalized Ddssmentioning

confidence: 99%

“…Furthermore, one of the in vivo models of female BALB/c mice employed in this study is based on the subcutaneous implantation of SP-exposed, mouse-derived HSCs and H22 cells. Altogether, the findings show that CAPS/GA-sHA-DOX NPs can inhibit the activation of HSCs, decrease drug resistance and metastasis of HCC cells by cutting off the cross-talk between HSCs and HCC cells, and promote cellular drug uptake by aHSCs and HCC cells through CD44 and GA receptors, respectively [ 64 ].…”

Section: Environment-responsive Ga-functionalized Ddssmentioning

confidence: 99%

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

et al. 2022

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Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient’s quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.

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Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting “substance P-hepatic stellate cells-hepatocellular carcinoma” axis

Cited by 42 publications

References 47 publications

GA&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

Recent advances in anti-multidrug resistance for nano-drug delivery system

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

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