Nano co-delivery of Plumbagin and Dihydrotanshinone I reverses immunosuppressive TME of liver cancer

Han, Shulan; Ning, Guiling; Guo, Tingting; Sun, Dandan; Zou, Yifang; Wang, Lingzhi; Liu, Song; Chu, Di; Liao, Anqi; Song, Xiaohuan; Yu, Zhuo; Guo, Jianfeng

doi:10.1016/j.jconrel.2022.05.057

Cited by 48 publications

(33 citation statements)

References 61 publications

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“…Recent studies have shown that the tumor microenvironment is closely related to the progression, prognosis, and drug resistance of HCC. However, most current tumor treatment strategies only target tumor cells, ignoring the important role of the tumor microenvironment, so many patients will experience recurrence and metastasis after treatment [ 3 , 42 ]. Admittedly, a single antifibrotic drug has certain limitations, and it may still be insufficient in further cancer microenvironment therapy.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In recent years, the combination of NPs and medicine has been strongly developed, and NPs have obvious advantages such as low poison, noninvasive, and good biocompatibility. Applying this new drug-loading system, researchers can make better use of multifunctional therapeutic strategies to improve the efficiency of exploring anticancer [42,43]. We constructed a multifunctional integrated nanodrug delivery system by encapsulating the phase-change material PFP and the antifibrotic drug PFD with lipid material as the outer structure, which further improved the efficiency of PFD drug action.…”

Section: Discussionmentioning

confidence: 99%

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Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells

Zou

Mao

et al. 2022

BioMed Research International

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Objectives. Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs). Methods. PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining. Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6 ± 62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm2, it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGFβ-Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV. Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells

Zou

Mao

et al. 2022

BioMed Research International

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“…Han S et al (36) used a poly (D,L-lactic-co-glycolic acid) (PLGA)based nanoparticle (NP) to co-encapsulate dihydrotanshinone I (DIH) and two other drugs, generating chemo-immunotherapeutic effects to reverse an immunosuppressive tumor microenvironment and found significantly increased survival among mice with hepatocellular carcinoma (HCC), without associated toxic signs.…”

Section: Regulation Of the Innate Immune Systemmentioning

confidence: 99%

Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment

Sun

Wang

et al. 2022

Front. Oncol.

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Traditional Chinese medicine (TCM), including herbal medicine, acupuncture and meditation, has a wide range of applications in China. In recent years, herbal compounding and active ingredients have been used to control tumor growth, reduce suffering, improve quality of life, and prolong the life span of cancer patients. To reduce side effects, herbal medicine can be used in conjunction with radiotherapy and chemotherapy or can be used as an adjuvant to strengthen the immune effect of anticancer vaccines. In particular, in the immunosuppressed tumor microenvironment, herbal medicine can have antitumor effects by stimulating the immune response. This paper reviews the advances in research on antitumor immunomodulation in Chinese herbal medicine, including the regulation of the innate immune system, which includes macrophages, MDSCs, and natural killer cells, and the adaptive immune system, which includes CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs), to influence tumor-associated inflammation. In addition, a combination of active ingredients of herbal medicine and modern nanotechnology alter the tumor immune microenvironment. In recent years, immunological antitumor therapy in TCM has been applied on a reasonably large scale both nationally and internationally, and there is potential for further clinical expansion. Investigation of immune modulation mechanisms in Chinese herbal medicine will provide novel perspectives of how herbal medicine controls tumor growth and metastasis, which will contribute to the evolution of tumor research.MethodologyExperimental research between the years of 2012-2022, meta-analysis and reviews for the period 2002-2022 found on the Databases including PubMed, Embase, and the Cochrane database were used. The inclusion criteria were experimental research literature addressing the anti-tumor immunological effects of active ingredients and nanoparticles in Chinese herbal medicine. Exclusion criteria were articles that addressed Chinese herbal medicine and nano-formulations without discussing anti-tumor immunological effects in innate, adaptive immune cells, MDSCs, and nuclear factors.

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“…HCC accounts for more than 85%–90% of cases, with a high degree of malignancy, and is prone to recurrence and metastasis ( Pan et al, 2021 ; Khatib et al, 2022 ). Traditional chemotherapy as a common treatment option can lead to cure and life prolongation for patients with HCC, yet the prognosis for most patients is dire or poor ( Fu et al, 2022 ; Han et al, 2022 ). Therefore, the quest for potent new drugs for the treatment of HCC is paramount.…”

Section: Introductionmentioning

confidence: 99%

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Feng

Pan

et al. 2022

Front. Pharmacol.

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Schisantherin A (STA) is a traditional Chinese medicine extracted from the plant Schisandra chinensis, which has a wide range of anti-inflammatory, antioxidant, and other pharmacological effects. This study investigates the anti-hepatocellular carcinoma effects of STA and the underlying mechanisms. STA significantly inhibits the proliferation and migration of Hep3B and HCCLM3 cells in vitro in a concentration-dependent manner. RNA-sequencing showed that 77 genes are upregulated and 136 genes are downregulated in STA-treated cells compared with untreated cells. KEGG pathway analysis showed significant enrichment in galactose metabolism as well as in fructose and mannose metabolism. Further gas chromatography-mass spectrometric analysis (GC-MS) confirmed this, indicating that STA significantly inhibits the glucose metabolism pathway of Hep3B cells. Tumor xenograft in nude mice showed that STA has a significant inhibitory effect on tumor growth in vivo. In conclusion, our results indicate that STA can inhibit cell proliferation by regulating glucose metabolism, with subsequent anti-tumor effects, and has the potential to be a candidate drug for the treatment of liver cancer.

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Nano co-delivery of Plumbagin and Dihydrotanshinone I reverses immunosuppressive TME of liver cancer

Cited by 48 publications

References 61 publications

Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells

Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells

Antitumor effects of Chinese herbal medicine compounds and their nano-formulations on regulating the immune system microenvironment

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

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