With advances of drug design and preparation technology, the development of long-acting drugs has become an important research focus in precision medicine and chronic disease management. These drugs are designed to improve the patients' compliance and quality of life by achieving prolonged maintenance of an effective drug concentration in the body with a reduced dosing frequency. Small molecule drugs, monoclonal antibodies and nucleic acid drugs all have their own difficulties in achieving long actions, which can be especially challenging for the latter two because of their structural complexity. This review provides an overview of the strategies for designing long-acting small molecule drugs, monoclonal antibodies, and nucleic acid drugs.
Humans ; Drug Design ; Antibodies, Monoclonal/chemistry* ; Nucleic Acids ; Precision Medicine ; Delayed-Action Preparations

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*

With the emergence of DNA nanotechnology in the 1980s, self-assembled DNA nanostructures have attracted considerable attention worldwide due to their inherent biocompatibility, unsurpassed programmability, and versatile functions. Especially promising nanostructures are tetrahedral framework nucleic acids (tFNAs), first proposed by Turberfield with the use of a one-step annealing approach. Benefiting from their various merits, such as simple synthesis, high reproducibility, structural stability, cellular internalization, tissue permeability, and editable functionality, tFNAs have been widely applied in the biomedical field as three-dimensional DNA nanomaterials. Surprisingly, tFNAs exhibit positive effects on cellular biological behaviors and tissue regeneration, which may be used to treat inflammatory and degenerative diseases. According to their intended application and carrying capacity, tFNAs could carry functional nucleic acids or therapeutic molecules through extended sequences, sticky-end hybridization, intercalation, and encapsulation based on the Watson and Crick principle. Additionally, dynamic tFNAs also have potential applications in controlled and targeted therapies. This review summarized the latest progress in pure/modified/dynamic tFNAs and demonstrated their regenerative medicine applications. These applications include promoting the regeneration of the bone, cartilage, nerve, skin, vasculature, or muscle and treating diseases such as bone defects, neurological disorders, joint-related inflammatory diseases, periodontitis, and immune diseases.
Nucleic Acids/chemistry* ; Regenerative Medicine ; Consensus ; Reproducibility of Results ; DNA/chemistry*

The lipid droplet (LD) is a unique multi-functional organelle that contains a neutral lipid core covered with a phospholipid monolayer membrane. The LDs have been found in almost all organisms from bacteria to humans with similar shape. Several conserved functions of LDs have been revealed by recent studies, including lipid metabolism and trafficking, as well as nucleic acid binding and protection. We summarized these findings and proposed a hypothesis that the LD is a conserved organelle.
Animals ; Bacteria ; metabolism ; ultrastructure ; Biological Evolution ; Cholesterol Esters ; metabolism ; Humans ; Lipid Droplets ; chemistry ; metabolism ; ultrastructure ; Lipid Metabolism ; genetics ; Nucleic Acids ; metabolism ; Peptide Initiation Factors ; chemistry ; metabolism ; Protein Binding ; RNA-Binding Proteins ; chemistry ; metabolism ; Ribosome Subunits ; chemistry ; metabolism ; Triglycerides ; metabolism

Peptide nucleic acid (PNA) is a DNA surrogate in which the phosphate deoxyribose backbone of DNA is replaced by repeating N-(2-aminoethyl)glycine units. PNA can hybridize to the complementary DNA and RNA with higher affinity than their oligonucleotide counterparts. This character of PNA not only makes it a new tool for the studies of molecular biology but also the potential candidate for gene-targeting drugs. The non-ionic backbone of PNA leads to stable hybrids with the nucleic acids, but at the same time, the neutral backbone results in poor cellular uptake. To address this problem, studies on modified PNA progress rapidly in recent years. We reviewed literature reports combined with our study about the delivery methods, including backbone modified PNA and PNA-ligand conjugates, and the cellular uptake of modified PNA. In addition, we summarized the problems and future prospect of the cellular delivery of modified PNA.
DNA, Complementary ; Drug Delivery Systems ; Glycine ; analogs & derivatives ; Humans ; Nucleic Acid Hybridization ; Oligonucleotides ; Peptide Nucleic Acids ; chemistry ; RNA

As a novel branch of combinational chemistry, dynamic combinatorial chemistry (DCC) can be viewed as a technique which combines library synthesis and screening in one pot. By addition of molecular target, ligangds, which show binding affinity or strong interaction with the molecular target, can be amplified an young but rapidly growing branch of combinatorial chemistry, has been widely used in organic chemistry, biochemistry, material fields. Ligands in the library can be amplified, since synthesis of the library is screened by a molecular target. Therefore, these structures could be identified easily. Consequently DCC has been widely used in the lead discovery, material chemistry and other fields. On the basis of the principle and method of DCC, this review emphasizes the three factors of DCC, including molecular targets (bio-enzyme, lectin, nucleic acid, organic molecule, inorganic molecule); reaction (disulphide chemistry, ammoniation reduction reaction, hydrazone chemistry, etc.) and analytical method. Meanwhile, limitation, current situation and future development of DCC were also discussed in this paper.
Combinatorial Chemistry Techniques ; methods ; Enzymes ; chemistry ; Lectins ; chemistry ; Nucleic Acids ; chemistry

BACKGROUND: A peptide nucleic acid (PNA) probe-based real-time PCR (PNAqPCR(TM) TB/NTM detection kit; PANAGENE, Korea) assay has been recently developed for the simultaneous detection of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) in clinical specimens. The study was aimed at evaluation of the performance of PNA probe-based real-time PCR in respiratory specimens. METHODS: To evaluate potential cross-reactivity, the extracted DNA specimens from Mycobacterium species and non-mycobacterial species were tested using PNA probe-based real-time PCR assay. A total of 531 respiratory specimens (482 sputum specimens and 49 bronchoalveolar washing fluid specimens) were collected from 230 patients in July and August, 2011. All specimens were analyzed for the detection of mycobacteria by direct smear examination, mycobacterial culture, and PNA probe-based real-time PCR assay. RESULTS: In cross-reactivity tests, no false-positive or false-negative results were evident. When the culture method was used as the gold standard test for comparison, PNA probe-based real-time PCR assay for detection of MTBC had a sensitivity and specificity of 96.7% (58/60) and 99.6% (469/471), respectively. Assuming the combination of culture and clinical diagnosis as the standard, the sensitivity and specificity of the new real-time PCR assay for detection of MTBC were 90.6% (58/64) and 99.6% (465/467), respectively. The new real-time PCR for the detection of NTM had a sensitivity and specificity of 69.0% (29/42) and 100% (489/489), respectively. CONCLUSIONS: The new real-time PCR assay may be useful for the detection of MTBC in respiratory specimens and for discrimination of NTM from MTBC.
Bronchoalveolar Lavage Fluid/microbiology ; DNA Probes/chemistry/metabolism ; DNA, Bacterial/*analysis ; Humans ; Molecular Typing/*methods ; Mycobacterium tuberculosis/*genetics/isolation & purification ; Nontuberculous Mycobacteria/*genetics/isolation & purification ; Nucleic Acid Hybridization ; Peptide Nucleic Acids/chemistry/*metabolism ; *Real-Time Polymerase Chain Reaction ; Respiratory System/*microbiology ; Sputum/microbiology

Liposome-mediated nucleic acid delivery has been a focus recently, but in the course of delivering nucleic acid, some hurdles seriously limit the nucleic acid exerting treatment effect. This review refers to a series of problems such as low blood stability, reticuloendothelial system absorption, the lower targeting of liposome and the restriction of endosomal escape which are suffered in liposome-mediated nucleic acid delivery; and gives a detail introduction of strategies such as PEGylation, ligand modification, photochemical internalization, the application of degradation liposome and membrane-lytic peptide, to overcome those problems.
Animals ; Humans ; Liposomes ; chemistry ; pharmacokinetics ; Mononuclear Phagocyte System ; metabolism ; Nanoparticles ; Nucleic Acids ; chemistry ; pharmacokinetics ; Photochemical Processes ; Polyethylene Glycols ; chemistry ; pharmacokinetics ; Polymers ; chemistry

OBJECTIVETo investigate the characteristics of freshly resected laryngeal carcinoma by Fourier transform infrared spectroscopy (FTIR).

METHODSFTIR was applied to the study of the cancerous tissues and adjacent normal tissues in 32 patients.

RESULTSCompared with pathological diagnosis results, one benign specimen was classified as a malignant, the accuracy was 98.4%. Significant differences were seen in the FTIR spectra between the normal and malignant laryngeal tissues. The peak at 1085 cm(-1) shift to 1114 cm(-1) showed that the relative contents of DNA in laryngeal carcinoma cells was increased. The peak at 1397 cm(-1) was stronger than 1451 cm(-1) in normal tissues, while it was not obvious in cancer tissues. I(2926)/I(2870) in carcinoma cells was lower than that in normal tissues. The wave numbers of the bands of amide I and amide II, symmetric and asymmetric stretching bands of CH(3), stretching vibration bands of C-OH and NH band were shifted to higher number in cancer tissues.

CONCLUSIONThe study shows that the malignant and normal laryngeal tissues have different FTIR spectra, which are mainly due to changes in protein, nucleic acid and phospholipids. FTIR may become a new method for the diagnosis of laryngeal carcinoma in clinical practice.

Humans ; Laryngeal Neoplasms ; chemistry ; diagnosis ; pathology ; Larynx ; chemistry ; pathology ; Neoplasm Proteins ; analysis ; Nucleic Acids ; analysis ; Phospholipids ; analysis ; Spectroscopy, Fourier Transform Infrared ; methods

OBJECTIVETo investigate the effect of polysaccharide nucleic acid of BCG (BCG-PSN) injection on immune and pulmonary function in asthmatic children complicated with allergic rhinitis.

METHODSThirty-seven cases were separated at random into two groups, the BCG-PSN group (17 cases) was treated with BCG-PSN plus inhaled glucocortisteriods, and the control group (20 cases) was treated with inhaled glucocortisteriods only. The children in both groups were followed up for 6 months to record their lung function, allergic rhinitis scores, frequency of asthmatic attacks and respiratory infection. The levels of interleukin (IL)-4, interferon-gamma (IFN-g) and plasma total IgE were detected by using double antibody sandwich ELISA at the beginning and the end of treatment.

RESULTSIn comparison with the control group, after treatment, the levels of IFN-g and the ratio of IFN-g/IL4 in the BCG-PSN group significantly increased, whereas the level of IL-4 and the plasma total IgE significantly decreased (P less than 0.05), while those of the control group had no significant change. The lung function of both groups had significant improvement (p less than 0.05). The frequencies of asthmatic attacks in BCG-PSN and control groups were 0.81 +/- 0.20 vs. 1.72 +/- 0.80, and the difference was statistically significant. The frequencies of respiratory tract infection in BCG-PSN and control groups were 1.15 +/- 0.55 vs. 3.21 +/- 0.73, the difference was significant.

CONCLUSIONBCG-PSN may be able to correct the imbalance of Th1/Th2 and improve the lung function of children with asthma complicated with allergic rhinitis, which suggest that the immune adjusting treatment should be emphasized besides anti-inflammation therapy.

Adjuvants, Immunologic ; chemistry ; therapeutic use ; Adolescent ; Asthma ; blood ; complications ; drug therapy ; BCG Vaccine ; chemistry ; therapeutic use ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Nucleic Acids ; chemistry ; Polysaccharides, Bacterial ; chemistry ; Rhinitis, Allergic, Perennial ; blood ; complications ; drug therapy ; Treatment Outcome