Dataset Information

Targeted codelivery of doxorubicin and IL-36? expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.

ABSTRACT: Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36? expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36? plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded with Dox only. Gene transfection in both lungs and s.c. tumors was significantly higher with our polymer compared to PEI. In addition, the Dox?+?IL-36?/POEG-st-Pmor not only could bring improved anti-metastatic effect but synergistically enhance the type I immune response by increasing the IFN-? positive CD4+ and CD8+ T cells and simultaneously decreasing the immunosuppressive myeloid-derived suppressor cells in the lung. POEG-st-Pmor may represent a simple and effective delivery system for an optimal chemo-gene combination therapy.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6289619 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.

Chen Yichao Y Sun Jingjing J Huang Yixian Y Liu Yanhua Y Liang Lei L Yang Da D Lu Binfeng B Li Song S

Nanomedicine : nanotechnology, biology, and medicine 20181008 1

Cancer metastasis is the main cause for the high mortality in breast cancer patients. In this work we developed a polymer POEG-st-Pmor for targeted co-delivery of IL-36γ expression plasmid and doxorubicin (Dox) to lung metastasis of breast cancer. The polymer readily formed micelles that were effective in loading Dox and simultaneously forming complexes with IL-36γ plasmid. Interestingly, particles co-loaded with Dox and plasmid was significantly smaller and more stable than the particles loaded ...[more]

PMID: 30308300

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Project description:Chronic hepatitis B is a critical cause of many serious liver diseases such as hepatocellular carcinoma (HCC). The main challenges in hepatitis B treatment include the rebound of hepatitis B virus (HBV)-related antigen levels after drug withdrawal and the immunosuppression caused by the virus. Herein, we demonstrate that the HBV-related antigen can be effectively inhibited and antiviral immunity can be successfully reactivated through codelivery of the small interfering RNA (siRNA) targeting HBV X protein (HBx) and the plasmid encoding interleukin 12 (pIL-12) to hepatocytes and immune cells. After being treated by the siRNA/pIL-12 codelivery system, HBx mRNA and hepatitis B surface antigen (HBsAg) are dramatically reduced in HepG2.215 cells. More importantly, the downregulated CD47 and programmed death ligand 1 (PD-L1) and the upregulated interferon-β promoter stimulator-1 (IPS-1), retinoic acid-inducible gene-1 (RIG-1), CD80, and human leukocyte antigen-1 (HLA-1) in treated HepG2.215 cells indicate that the immunosuppression is reversed by the codelivery system. Furthermore, the codelivery system results in inhibition of extracellular regulated protein kinases (ERK) and phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathways, as well as downregulation of B-cell lymphoma-2 (Bcl-2) and upregulation of p53, implying its potential in preventing the progression of HBV-induced HCC. In addition, J774A.1 macrophages treated by the codelivery system were successfully differentiated into the M1 phenotype and expressed enhanced cytokines with anti-hepatitis B effects such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Therefore, we believe that codelivery of siRNA and pIL-12 can effectively inhibit hepatitis B virus, reverse virus-induced immunosuppression, reactivate antiviral immunity, and hinder the progression of HBV-induced hepatocellular carcinoma. This investigation provides a promising approach for the synergistic treatment of HBV infection.

Dataset Information

Targeted codelivery of doxorubicin and IL-36? expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.

Publications

Targeted codelivery of doxorubicin and IL-36γ expression plasmid for an optimal chemo-gene combination therapy against cancer lung metastasis.

Similar Datasets

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