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Journal of Biomedical Materials... Nov 2020Doxorubicin shows good anticancer activity, but poor pharmacokinetic property and high organ toxicity restrict its clinical application. The synthesized phenylboronic...
Doxorubicin shows good anticancer activity, but poor pharmacokinetic property and high organ toxicity restrict its clinical application. The synthesized phenylboronic acid-modified F127-chitosan conjugate was used to prepare doxorubicin-loaded micelles through dialysis method. The physicochemical properties of the doxorubicin-loaded micelles were characterized. These micelles were further evaluated for in vitro release/cytotoxicity, in vivo activity/biosafety, and pharmacokinetic studies. in vitro release experiment demonstrated that the release of doxorubicin from drug-loaded micelles was pH-dependent. in vitro cytotoxic study showed that the introduction of phenylboronic acid resulted in lower IC against B16 cells than that in non-modified F127-chitosan micelles group, and the doxorubicin-loaded micelles displayed lower in vitro activity against B16, A549, and HT-29 cells than free doxorubicin did. However, in vivo experiments confirmed that the doxorubicin-loaded micelles were safe for mouse main organs, obviously improved pharmacokinetic parameters of doxorubicin in rat and achieved comparable inhibition of tumor growth with no animal death in B16-bearing mice models throughout the experiment when compared with free doxorubicin. The phenylboronic acid-sialic acid interaction and pH-sensitive drug release might play important roles in increased tumor targeting and therapeutic effect of the doxorubicin-loaded micelles.
Topics: A549 Cells; Animals; Antibiotics, Antineoplastic; Boronic Acids; Cell Line, Tumor; Cell Survival; Chitosan; Doxorubicin; Drug Delivery Systems; Drug Liberation; HT29 Cells; Humans; Melanoma, Experimental; Mice; Micelles; Oligosaccharides; Particle Size; Rats; Rats, Sprague-Dawley
PubMed: 32583518
DOI: 10.1002/jbm.b.34670 -
European Urology Jun 2023
Topics: Humans; Mitomycin; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Antibiotics, Antineoplastic; Hyperthermia, Induced; Administration, Intravesical
PubMed: 36967360
DOI: 10.1016/j.eururo.2023.03.004 -
Cancer Letters Sep 2020The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and...
The dependency of prostate cancer (PCa) growth on androgen receptor (AR) signaling has been harnessed to develop first-line therapies for high-risk localized and metastatic PCa treatment. However, the occurrence of aberrant expression, mutated or splice variants of AR confers resistance to androgen ablation therapy (ADT), radiotherapy or chemotherapy in AR-positive PCa. Therapeutic strategies that effectively inhibit the expression and/or transcriptional activity of full-length AR, mutated AR and AR splice variants have remained elusive. In this study, we report that mithramycin (MTM), an antineoplastic antibiotic, suppresses cell proliferation and exhibits dual inhibitory effects on expression and transcriptional activity of AR and AR splice variants. MTM blocks AR recruitment to its genomic targets by occupying AR enhancers and causes downregulation of AR target genes, which includes key DNA repair factors in DNA damage repair (DDR). We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.
Topics: Antibiotics, Antineoplastic; Cell Line, Tumor; DNA Damage; DNA Repair; Humans; Male; Plicamycin; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 32485222
DOI: 10.1016/j.canlet.2020.05.027 -
Journal of Nuclear Cardiology :... Feb 2022
Topics: Anthracyclines; Antibiotics, Antineoplastic; Free Radicals; Humans; Molecular Imaging
PubMed: 32627135
DOI: 10.1007/s12350-020-02254-6 -
The Journal of Antibiotics Aug 2019A new catecholate-containing siderophore, labrenzbactin (1), was isolated from the fermentation broth of a coral-associated bacterium Labrenzia sp. The structure and...
A new catecholate-containing siderophore, labrenzbactin (1), was isolated from the fermentation broth of a coral-associated bacterium Labrenzia sp. The structure and absolute configuration of 1 was determined by spectroscopic methods and Marfey's analysis. Overall, 1 showed antimicrobial activity against Ralstonia solanacearum SUPP1541 and Micrococcus luteus ATCC9341 with MIC values of 25 and 50 µg ml, respectively, and cytotoxicity against P388 murine leukemia cells with an IC of 13 µM.
Topics: Alphaproteobacteria; Animals; Anthozoa; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Catechols; Drug Screening Assays, Antitumor; Fermentation; Leukemia P388; Mice; Microbial Sensitivity Tests; Micrococcus luteus; Molecular Structure; Oxazoles; Ralstonia; Siderophores
PubMed: 31118481
DOI: 10.1038/s41429-019-0192-x -
Journal of Natural Products Sep 2020The new alkaloids marinacarbolines E-Q (-, -), caerulomycin N (), and actinoallonaphthyridine A (), together with the known marinacarboline C () and cyanogramide (),...
The new alkaloids marinacarbolines E-Q (-, -), caerulomycin N (), and actinoallonaphthyridine A (), together with the known marinacarboline C () and cyanogramide (), were isolated from the actinomycete sp. ZZ1866. The structures of the isolated compounds were elucidated based on their HRESIMS data, extensive NMR spectroscopic analyses, Mosher's method, ECD calculations, single-crystal X-ray diffraction analysis, and chemical degradation studies. Marinacarbolines E-L (-) share an indolepyridone-imidazole tetracyclic skeleton, which is the first example of this kind of skeleton. Caerulomycin N () and cyanogramide () exhibited cytotoxic activity against both human glioma U251 and U87MG cells with IC values of 2.0-7.2 μM. Marinacarbolines E (), G (), I (), and M () showed cytotoxic activity against U87MG cells with IC values of 2.3-8.9 μM.
Topics: Actinobacteria; Alkaloids; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Bacteria; Cell Line, Tumor; Circular Dichroism; Fungi; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Spectrometry, Mass, Electrospray Ionization; X-Ray Diffraction
PubMed: 32864967
DOI: 10.1021/acs.jnatprod.0c00588 -
Journal of Vascular and Interventional... Aug 2019This study compared loading, elution, and stability of drug-eluting embolic beads (DEBs) loaded with idarubicin. (Comparative Study)
Comparative Study
PURPOSE
This study compared loading, elution, and stability of drug-eluting embolic beads (DEBs) loaded with idarubicin.
MATERIALS AND METHODS
DC Bead (100-300 μm), HepaSphere (30-60 μm), LifePearl (200 μm), and Tandem (100 μm) DEBs were loaded with 5 mg/mL idarubicin. Loading, elution, diameter changes, loading stability over 2 weeks in storage, and time in suspension were determined for each of the DEBs.
RESULTS
Loading of more than 99% of idarubicin was achieved within 15 minutes for LifePearl, DC Bead, and Tandem beads. LifePearl, DC Bead, HepaSphere, and Tandem beads eluted 75% of the total idarubicin released in 13, 24, 42, and 91 minutes, respectively. In vitro elution was completed in 2 hours with 73% ± 3%, 74% ± 3%, 65% ± 6%, and 7% ± 0% of the loaded idarubicin eluted for LifePearl, DC Bead, HepaSphere, and Tandem, respectively. Statistically significant differences were observed at every time point between at least 2 of the products. Overall, in vitro idarubicin elution was rapid and nearly complete for LifePearl, DC Bead, and HepaSphere beads but was minimal and slow from Tandem beads. The average diameter of DEBs after loading was reduced by 5% for LifePearl, whereas it was increased by 9% and 1% for DC Bead and Tandem, respectively. After loading, time in suspension was 11 ± 4 and 10 ± 2 minutes for LifePearl and HepaSphere, respectively, whereas DC Bead and Tandem beads were held in suspension for greater than 20 minutes.
CONCLUSIONS
Although all 4 DEBs loaded idarubicin within 15 minutes with minimal changes in diameter, the elution amounts, rates of release, and time in suspension varied.
Topics: Antibiotics, Antineoplastic; Chemoembolization, Therapeutic; Drug Carriers; Drug Liberation; Drug Stability; Drug Storage; Idarubicin; Kinetics; Microspheres; Particle Size
PubMed: 31155500
DOI: 10.1016/j.jvir.2018.12.022 -
Bioconjugate Chemistry Aug 2021Photoactivatable ligand proteins are potentially useful for light-induced intracellular delivery of therapeutic and diagnostic cargos through receptor-mediated cellular...
Photoactivatable ligand proteins are potentially useful for light-induced intracellular delivery of therapeutic and diagnostic cargos through receptor-mediated cellular uptake. Here, we report the simple and effective caging of transferrin (Tf), a representative ligand protein with cellular uptake ability, which has been used in the delivery of various cargos. Tf was modified with several biotin molecules through a photocleavable linker, and then the biotinylated Tf (bTf) was conjugated with the biotin-binding protein, streptavidin (SA), to provide steric hindrance to block the interaction with the Tf receptor. Without exposure to light, the cellular uptake of the bTf-SA complex was effectively inhibited. In response to light exposure, the complex was degraded with the release of Tf, leading to cellular uptake of Tf. Similarly, the cellular uptake of Tf-doxorubicin (Dox) conjugates could be suppressed by caging with biotinylation and SA binding, and the intracellular delivery of Dox could be triggered in a light-dependent manner. The intracellularly accumulated Dox decreased the cell viability to 25% because of the cell growth inhibitory effect of Dox. These results provided proof of principle that the caged Tf can be employed as a photoactivatable molecular device for the intracellular delivery of cargos.
Topics: Antibiotics, Antineoplastic; Biotinylation; Cell Line, Tumor; Delayed-Action Preparations; Doxorubicin; Humans; Light; Models, Molecular; Neoplasms; Transferrin
PubMed: 34328322
DOI: 10.1021/acs.bioconjchem.1c00159 -
Drug Delivery Dec 2021Bleomycin (BLM) is being repositioned in dermato-oncology for intralesional and intra-tumoural use. Although conventionally administered by local needle injections...
Bleomycin administered by laser-assisted drug delivery or intradermal needle-injection results in distinct biodistribution patterns in skin: investigations with mass spectrometry imaging.
Bleomycin (BLM) is being repositioned in dermato-oncology for intralesional and intra-tumoural use. Although conventionally administered by local needle injections (NIs), ablative fractional lasers (AFLs) can facilitate topical BLM delivery. Adding local electroporation (EP) can augment intracellular uptake in the target tissue. Here, we characterize and compare BLM biodistribution patterns, cutaneous pharmacokinetic profiles, and tolerability in an pig model following fractional laser-assisted topical drug delivery and intradermal NI, with and without subsequent EP. pig skin was treated with AFL and topical BLM or NI with BLM, alone or with additional EP, and followed for 1, 2 and 4 h and eventually up to 9 d. BLM biodistribution was assessed by spatiotemporal mass spectrometry imaging. Cutaneous pharmacokinetics were assessed by mass spectrometry quantification and temporal imaging. Tolerability was evaluated by local skin reactions (LSRs) and skin integrity measurements. AFL and NI resulted in distinct BLM biodistributions: AFL resulted in a horizontal belt-shaped BLM distribution along the skin surface, and NI resulted in BLM radiating from the injection site. Cutaneous pharmacokinetic analyses and temporal imaging showed a substantial reduction in BLM concentration within the first few hours following administration. LSRs were tolerable overall, and all interventions permitted almost complete recovery of skin integrity within 9 d. In conclusion, AFL and NI result in distinct cutaneous biodistribution patterns and pharmacokinetic profiles for BLM applied to skin. Evaluation of LSRs showed that both methods were similarly tolerable, and each method has potential for individualized approaches in a clinical setting.
Topics: Administration, Cutaneous; Animals; Antibiotics, Antineoplastic; Bleomycin; Electroporation; Female; Injections, Intradermal; Lasers, Gas; Mass Spectrometry; Skin; Skin Absorption; Swine
PubMed: 34121567
DOI: 10.1080/10717544.2021.1933649 -
Biotransformation of Doxorubicin Promotes Resilience in Simplified Intestinal Microbial Communities.MSphere Jun 2021Chemotherapeutic drugs can cause harmful gastrointestinal side effects, which may be modulated by naturally occurring members of our microbiome. We constructed...
Chemotherapeutic drugs can cause harmful gastrointestinal side effects, which may be modulated by naturally occurring members of our microbiome. We constructed simplified gut-associated microbial communities to test the hypothesis that bacteria-mediated detoxification of doxorubicin (i.e., a widely used chemotherapeutic) confers protective effects on the human microbiota. Mock communities composed of up to five specific members predicted by genomic analysis to be sensitive to the drug or resistant via biotransformation and/or efflux were grown over three generational stages to characterize community assembly, response to perturbation (doxorubicin exposure), and resilience. Bacterial growth and drug concentrations were monitored with spectrophotometric assays, and strain relative abundances were evaluated with 16S rRNA gene sequencing. Bacteria with predicted resistance involving biotransformation significantly lowered concentrations of doxorubicin in culture media, permitting growth of drug-sensitive strains in monoculture. Such protective effects were not produced by strains with drug resistance conferred solely by efflux. In the mixed communities, resilience of drug-sensitive members depended on the presence and efficiency of transformers, as well as drug exposure concentration. Fitness of bacteria that were resistant to doxorubicin via efflux, though not transformation, also improved when the transformers were present. Our simplified community uncovered ecological relationships among a dynamic consortium and highlighted drug detoxification by a keystone species. This work may be extended to advance probiotic development that may provide gut-specific protection to patients undergoing cancer treatment. While chemotherapy is an essential intervention for treating many forms of cancer, gastrointestinal side effects may precede infections and risks for additional health complications. We developed an model to characterize key changes in bacterial community dynamics under chemotherapeutic stress and the role of bacterial interactions in drug detoxification to promote microbiota resilience. Our findings have implications for developing bio-based strategies to promote gut health during cancer treatment.
Topics: Antibiotics, Antineoplastic; Bacteria; Biotransformation; Doxorubicin; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Humans; Phylogeny; RNA, Ribosomal, 16S
PubMed: 34192503
DOI: 10.1128/mSphere.00068-21