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<P>Despite tremendous progress in chemotherapy, drug resistance remains a major challenge for anticancer treatment. The combinations of chemo-photothermal and chemo-chemo treatments have been reported to be potential solutions to overcome drug resistance. In this study, we developed a dual-in-dual synergistic therapy based on the use of dual anticancer drug-loaded graphene oxide (GO) stabilized with poloxamer 188 for generating heat and delivering drugs to kill cancer cells under near-infrared (NIR) laser irradiation. The nanocomparable system is stable and uniform in size, generating sufficient heat to induce cell death. Dual drugs (doxorubicin and irinotecan)-loaded GO (GO-DI) in combination with laser irradiation caused higher cytotoxicity than that caused by the administration of a free single drug as well as a combination of drugs and blank GO in various cancer cells, especially in MDA-MB-231 resistant breast cancer cells. Exposure to “hot” NIR and GO-DI activated the intrinsic apoptosis pathway, which was confirmed based on changes in the morphology of cell nuclei and overexpression of apoptosis-related proteins. On the basis of the results, the combined treatment showed a synergistic effect compared to the effect of chemotherapy or photothermal treatment alone, demonstrating higher therapeutic efficacy to overcome one of the most severe problem in anticancer therapy, that of intrinsic resistance to chemotherapeutics.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-51/acsami.5b10426/production/images/medium/am-2015-104266_0005.gif'></P>
Carbamates have been widely used due to their versatility such as intermediates in pharmaceuticals, pesticides, fertilizers or precursors of isocyanates. The conventional process for the production of carbamates involves the toxic usage of phosgene. The reductive of carbonylation of aromatic nitro compounds with carbon monoxide in the presence of alcohols has drawn much attention as a phosgene-free alternative to carbamates. There have been numerous attempts to afford carbamates from the reductive carbonylation of nitrobenzene facilitated by various complexes of transitional metals. In this research, N-heterocyclic carbene (NHC)-palladium(II) complexes have been investigated as active catalysts for the synthesis of carbamates. The results showed that the 97% yield of carbamates was obtained under the conditions at 1600C in 2 h in the presence of (NHC)-palladium(II) as main catalyst.
Tran, Tuan Hiep,Ramasamy, Thiruganesh,Choi, Ju Yeon,Nguyen, Hanh Thuy,Pham, Thanh Tung,Jeong, Jee-Heon,Ku, Sae Kwang,Choi, Han-Gon,Yong, Chul Soon,Kim, Jong Oh Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-
<P>The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-<I>b</I>-polyaspartic acid (PEG-<I>b</I>-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.</P>
<P><B>Abstract</B></P> <P>The expression of Toll-like receptors (TLRs) on antigen presenting cells, especially dendritic cells, offers several sensitive mediators to trigger an adaptive immune response, which potentially can be exploited to detect and eliminate pathogenic objects. Consequently, numerous agonists that target TLRs are being used clinically either alone or in combination with other therapies to strengthen the immune system in the battle against cancer. This review summarizes the roles of TLRs in tumor biology, and focuses on relevant TLR-dependent antitumor pathways and the conjugation of TLR agonists as adjuvants to nano- and micro-particles for boosting responses leading to cancer suppression and eradication.</P> <P><B>Statement of Significance</B></P> <P>Toll-like receptors (TLRs), which express on antigen presenting cells, such as dendritic cells and macrophages, play an important role in sensing pathogenic agents and inducing adaptive immunity. As a result, several TLR agonists have been investigating as therapeutic agents individually or in combination with other treatment modalities for cancer treatment through boosting the immune system. This review aims to focus on the roles of TLRs in cancer and TLR-dependent antitumor pathways as well as the use of different nano- or micro-particles bearing TLR agonists for tumor inhibition and elimination.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>