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Background Smart materials capable of responding to external stimuli are noteworthy candidates in designing drug delivery systems. In many of the recent research, temperature and pH have been recognized as the main stimulating factors in designing systems for anti-cancer drugs delivery systems. Purpose In this study, thermo and pH-responsive character of a nano-carrier drug delivery platform based on lysine modified poly (vinylcaprolactam) hydrogel conjugated with doxorubicin was assessed. Methods Poly (vinylcaprolactam) cross-linked with poly (ethyleneglycol) diacrylate was prepared via RAFT polymerization, and the prepared structure was linked with lysine through ring-opening. The anti-cancer drug doxorubicin, was linked to lysine moiety of the prepared structure via Schiff-base reaction. The prepared platform was characterized by 1 HNMR and FT-IR, while molecular weight characterization was performed by size exclusion chromatography. The temperature-responsive activity was evaluated using differential scanning calorimetry and dynamic light scattering. In vitro release pattern in simulated physiologic pH at 37°C was compared with acidic pH attributed to tumor site and elevated temperature. The anticancer efficiency of the drug-conjugated structure was evaluated in breast cancer cell line MCF-7 in 24 and 48 h, and cell uptake assay was performed on the same cell line. Conclusion According to the results, well-structure defined smart pH and temperature responsive nano-hydrogel was prepared. The enhanced release rates are observed at acidic pH and elevated temperature. We have concluded that the doxorubicin-conjugated nanoparticle results in higher cellular uptakes and more cytotoxicity.

Based on the results, we hypothesize that aberrant surface expression of TLR9 on tumor cells may promote tumor growth and invasion. It might also highlight a dual contradictory role for CpG-ODNs, as adjutant in cancer therapy.

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The immune‐modulatory effect of adipose‐derived stem cells (ASCs) on B cells in cancer has not been well elucidated. Herein, the interaction between B cells and ASCs isolated from the breast fat of either normal (nASCs) or breast cancer women (cASCs) was investigated. B cells derived from breast tumor draining lymph nodes were co‐cultured with nASCs or cASCs and B cells proliferation was assessed in direct and transwell assays. Moreover, B cells were co‐cultured with cASCs, nASCs or mesenchymal stromal cells of the tumor tissue (TSCs) and B cell cytokine production was assessed using flow cytometery. cASCs or TSCs were co‐cultured with either intact or B cell depleted lymphocytes and frequencies of CD25+FoxP3+ Tregs, IL‐10+ or IFN‐γ+CD4+ T cells were assessed. Results showed that co‐culture of B cells with ASCs in transwell chambers did not affect B cell proliferation. nASCs, however, was able to significantly reduce B cell proliferation in direct co‐culture experiments (P = 0.004). The frequencies of IL‐10+, TNF‐α+, IL‐2+, and IFN‐γ+ B cells were not significantly different in the co‐cultures of B cells with ASCs or TSCs. But the TNF‐α+/ IL‐10+ B cells ratio decreased in all co‐cultures, a reduction merely significant in B cell‐cASCs co‐culture (P = 0.01). The frequencies of CD4+ T cells subsets in either intact or B cell depleted lymphocytes did not undergo significant changes following co‐culture with ASCs or TSCs. Therefore, ASCs is capable of inhibiting B cell proliferation in a contact dependent manner and shifting the cytokine profile of B cells toward an anti‐inflammatory profile.

Omental adipose tissue may play crucial roles for tumor promotion through the expression of tumor promoting chemokines. Accordingly, tumor surrounding adipose tissue may be a novel target for immunotherapy of cancer.

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The development of metastasis severely reduces the life expectancy of patients with colorectal cancer (CRC). Although loss of SMAD4 is a key event in CRC progression, the resulting changes in biological processes in advanced disease and metastasis are not fully understood. Here, we applied a multiomics approach to a CRC organoid model that faithfully reflects the metastasis-supporting effects of SMAD4 inactivation. We show that loss of SMAD4 results in decreased differentiation and activation of pro-migratory and cell proliferation processes, which is accompanied by the disruption of several key oncogenic pathways, including the TGFβ, WNT, and VEGF pathways. In addition, SMAD4 inactivation leads to increased secretion of proteins that are known to be involved in a variety of pro-metastatic processes. Finally, we show that one of the factors that is specifically secreted by SMAD4-mutant organoids�DKK3�reduces the antitumor effects of natural killer cells (NK cells). Altogether, our data provide new insights into the role of SMAD4 perturbation in advanced CRC.