OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

OBJECTIVETo study the inhibitory effect of binding peptides on duck hepatitis B virus (DHBV) replication in duck hepatocytes.

METHODSSpecific binding peptides to duck hepatitis B virus polymerase (DHBVP) were screened by phage display technology (PDT), then were sequenced and synthesized. Binding peptides were added into primary culture of duck hepatocytes infected with DHBV in vitro. DHBV-DNA in the cytoplasm, cell nucleus and medium supernatant was assayed over time.

RESULTSSeven binding peptides were obtained after 3-round screening by PDT. Duck primary hepatocytes infected by DHBV were treated with above obtained binding peptides. The DHBV-DNA levels in medium supernatant and cytoplasm of duck hepatocytes treated with synthesized peptides (the 3rd and the 6th peptide) were significantly lower than those of control cells (P<0.05).

CONCLUSIONSpecific binding peptides to DHBVP could inhibit the replication of DHBV.

Animals ; Cells, Cultured ; Ducks ; Hepadnaviridae Infections ; virology ; Hepatitis B Virus, Duck ; drug effects ; genetics ; Hepatitis, Viral, Animal ; virology ; Hepatocytes ; virology ; Peptide Nucleic Acids ; pharmacology ; RNA-Directed DNA Polymerase ; metabolism ; Virus Replication ; drug effects

OBJECTIVETo investigate the efficiency of a peptide nucleic acid (PNA) delivery system by using liposome via PNA-DNA hybrids and to test the inhibitive action of antisense PNA on expression of multidrug resistance (MDR) related P-glycoprotein (P-gp) in human neuroblastoma cell line SK-N-SH.

METHODSTwo antisense PNAs were designed targeting at MDR-1 mRNA and then combined with partially complement DNAs respectively. The hybrids were delivered into cells using cationic liposome. The transfection efficiency, expression of P-gp and MDR-1 mRNA, intracellular adarimycin (ADM) were measured by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and high performance liquid chromatography (HPLC).

RESULTSTransfection of PNA increased the cell average fluorescence intensity significantly and the extent of increase was dependent on the concentration of PNA. After being transfected by both PNAs, P-gp expression of SK-N-SH cells decreased significantly and the intracellular ADM level was increased by about 3 times. The level of MDR-1 mRNA expression slightly decreased after transfection, but no statistical significance was observed.

CONCLUSIONSPNA can be delivered into tumor cells in form of PNA-DNA hybrids by cationic liposome. Properly designed antisense PNA can inhibit MDR related P-gp expression of SK-N-SH cells efficiently and specifically.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Animals ; Drug Resistance, Multiple ; genetics ; Humans ; Nervous System Neoplasms ; metabolism ; Neuroblastoma ; metabolism ; Oligonucleotides, Antisense ; pharmacology ; Peptide Nucleic Acids ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Transfection ; Tumor Cells, Cultured

To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues. The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.
Adjuvants, Immunologic ; pharmacology ; Animals ; Female ; Immunocompromised Host ; Male ; Mice ; Mycobacterium bovis ; chemistry ; Nucleic Acids ; pharmacology ; Peptide Fragments ; pharmacology ; Polysaccharides, Bacterial ; pharmacology ; T-Lymphocyte Subsets ; drug effects ; Thymus Gland ; chemistry

To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues. The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.
Adjuvants, Immunologic/*pharmacology ; Immunocompromised Host ; Mycobacterium bovis/*chemistry ; Nucleic Acids/pharmacology ; Peptide Fragments/*pharmacology ; Polysaccharides, Bacterial/*pharmacology ; T-Lymphocyte Subsets/*drug effects ; Thymus Gland/chemistry

Peptide nucleic acid(PNA) is a kind of artificial DNA mimic. PNA hybridizes with DNA or RNA by means of Watson-Crick's base-pairs complementary with high stability, affinity and selectivity. PNA not only regulates. DNA replication, but also adjusts DNA transcription (or reverse transcription) and translation. Many applications have been explored as a new kind of molecular biological tool and a gene-targeting strategy.
Gene Expression Regulation ; drug effects ; Peptide Nucleic Acids ; pharmacology ; Protein Biosynthesis ; drug effects ; Transcription, Genetic ; drug effects