-
Chembiochem : a European Journal of... Nov 2021To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are...
To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are severely limited by low drug loading capacity and adverse side effects. Here, a new type of metal-drug nanoparticles (MDNs) was designed and synthesized. The MDNs self-assembled with Fe(III) ions and drug molecules through coordination, resulting in nanoparticles with high drug loading. To assist systemic delivery and prolong circulation time, the obtained MDNs were camouflaged with red blood cell (RBCs) membranes (RBCs@Fe-DOX MDNs) to improve their stability and dispersity. The RBCs@Fe-DOX MDNs presented pH-responsive release functionalities, resulting in drug release accelerated in acidic tumor microenvironments. The outstanding in vitro and in vivo antitumor therapeutic outcome was realized by RBCs@Fe-DOX MDNs. This study provides an innovative design guideline for chemotherapy and demonstrates the great capacity of nanomaterials in anticancer treatments.
Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Cell Membrane; Cell Proliferation; Cell Survival; Doxorubicin; Drug Screening Assays, Antitumor; Erythrocytes; Ferric Compounds; Hydrogen-Ion Concentration; Mice; Molecular Structure; Nanoparticles; Neoplasms, Experimental; Particle Size
PubMed: 34468067
DOI: 10.1002/cbic.202100313 -
Journal of Controlled Release :... Jul 2017Injectable drug delivery systems that autonomously detect, propel towards, and ultimately treat the cancerous tissue, are the future of targeted medicine. Here, we...
Injectable drug delivery systems that autonomously detect, propel towards, and ultimately treat the cancerous tissue, are the future of targeted medicine. Here, we developed a drug delivery system that swims autonomously towards cancer cells, where it releases a therapeutic cargo. This platform is based on viable bacteria, loaded with nanoparticles that contain the chemotherapeutic-antibiotic drug doxorubicin. The bacteria ferry across media and invade the cancer cells, increasing their velocity in the presence of nutrients that are present within the tumor microenvironment. Inside the cancer cells, doxorubicin is released from the nanoparticles, destroying the bacterial swimmer (antibiotic activity) and executing the therapeutic activity against the cancer cells (chemotherapeutic activity). This mode of delivery, where both the carrier and the cancer cell are destroyed, supports implementing nanoswimmers in drug delivery (Fig. 1).
Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Escherichia coli; Liposomes; Mice; Neoplasms; Salmonella typhimurium
PubMed: 27744036
DOI: 10.1016/j.jconrel.2016.10.006 -
Advances in Protein Chemistry and... 2017Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations... (Review)
Review
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease. Ascochlorin (ASC), an isoprenoid antibiotic isolated initially from the fermented broth of Ascochyta viciae, and its synthetic derivatives have recently demonstrated substantial antineoplastic effects in a variety of tumor cell lines and mouse models. The major focus of this review article is to briefly analyze the chemopreventive as well as therapeutic properties of ASC and its derivatives and to identify the multiple molecular targets modulated by this novel class of anticancer agent.
Topics: Alkenes; Animals; Antibiotics, Antineoplastic; Apoptosis; Ascomycota; Autophagy; Humans; Neoplasm Invasiveness; Neoplasms; Phenols
PubMed: 28427561
DOI: 10.1016/bs.apcsb.2017.01.001 -
Critical Reviews in Analytical Chemistry 2023Epirubicin (EPI) is a chemotherapeutic agent belonging to the anthracycline drug class indicated for treating several tumors. It acts by suppressing the DNA and RNA... (Review)
Review
Epirubicin (EPI) is a chemotherapeutic agent belonging to the anthracycline drug class indicated for treating several tumors. It acts by suppressing the DNA and RNA synthesis by intercalating between their base pair. However, several side effects are associated with this therapy, including cardiotoxicity and myelosuppression. Therefore, EPI delivery in nanosystems has been an interesting strategy to overcome these limitations and improve the safety and efficacy of EPI. Thus, analytical methods have been used to understand and characterize these nanosystems, including spectrophotometric, spectrofluorimetric, and chromatography. Spectrophotometric and spectrofluorimetric methods have been used to quantify EPI in less complex matrices due to their efficiency, low cost, and green chemistry character. By contrast, high-performance liquid chromatography is a suitable method for detecting EPI in more complex matrices (e.g., plasm and urine) owing to its high sensitivity. This review summarizes physicochemical and pharmacokinetic properties of EPI, its application in drug delivery nanosystems, and the analytical methods employed in its quantification in different matrices, including blood, plasm, urine, and drug delivery nanosystems.
Topics: Epirubicin; Nanoparticles; Drug Delivery Systems; Antibiotics, Antineoplastic
PubMed: 34818953
DOI: 10.1080/10408347.2021.2007469 -
Recent Patents on Anti-cancer Drug... 2019Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and... (Review)
Review
BACKGROUND
Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells.
OBJECTIVE
An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view.
METHODS
Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides.
RESULTS
The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets.
CONCLUSION
These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.
Topics: Animals; Anti-Infective Agents; Antibiotics, Antineoplastic; Humans; Neoplasms; Patents as Topic; Peptide Fragments
PubMed: 30663573
DOI: 10.2174/1574892814666190119165157 -
Current Drug Metabolism 2017Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of... (Review)
Review
BACKGROUND
Anthracycline antibiotic doxorubicin (DOX) is a very potent and extensively prescribed chemotherapeutic drug. It is widely utilized in the therapy of variety of haematological and solid tumours, although its administration is commonly accompanied with several severe side effects. The most serious one is a development of dose-dependent and cumulative cardiotoxicity. In the course of time, many strategies have been investigated in order to avoid or at least to diminish DOX-induced cardiac dysfunction; these include reduction of toxic effect by coadministration with iron chelators (dexrazoxane), trastuzumab, taxanes, statins, and ACE-inhibitors. However, the attenuation of cardiotoxic effect is still not satisfactory yet.
OBJECTIVE
This review represents an overall appraisal of studies concerning with the utilization of various doxorubicinloaded nanoparticles in the cancer treatment with specific emphasis on those studies evaluating their influence on the reduction of heart tissue damage.
CONCLUSION
Introduction of nanoscale drug delivery systems undoubtedly represents nowadays one of the most promising tools for lowering systemic toxicity. Nanoparticles enable to target the therapeutic payload directly towards the tumor tissue, thus leading to the increased accumulation of the drug in the desired tissue and simultaneously protecting surrounding healthy tissues.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Drug Carriers; Humans; Nanoparticles; Neoplasms
PubMed: 28059036
DOI: 10.2174/1389200218666170105165444 -
Molecular Cancer Therapeutics Jun 2021Calicheamicin antibody-drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin)...
Calicheamicin antibody-drug conjugates (ADCs) are effective therapeutics for leukemias with two recently approved in the United States: Mylotarg (gemtuzumab ozogamicin) targeting CD33 for acute myeloid leukemia and Besponsa (inotuzumab ozogamicin) targeting CD22 for acute lymphocytic leukemia. Both of these calicheamicin ADCs are heterogeneous, aggregation-prone, and have a shortened half-life due to the instability of the acid-sensitive hydrazone linker in circulation. We hypothesized that we could improve upon the heterogeneity, aggregation, and circulation stability of calicheamicin ADCs by directly attaching the thiol of a reduced calicheamicin to an engineered cysteine on the antibody via a disulfide bond to generate a linkerless and traceless conjugate. We report herein that the resulting homogeneous conjugates possess minimal aggregation and display high stability with 50% of the drug remaining conjugated to the antibody after 21 days. Furthermore, these calicheamicin ADCs are highly efficacious in mouse models of both solid tumor (HER2 breast cancer) and hematologic malignancies (CD22 non-Hodgkin lymphoma). Safety studies in rats with this novel calicheamicin ADC revealed an increased tolerability compared with that reported for Mylotarg. Overall, we demonstrate that applying novel linker chemistry with site-specific conjugation affords an improved, next-generation calicheamicin ADC.
Topics: Animals; Antibiotics, Antineoplastic; Calicheamicins; Disease Models, Animal; Humans; Immunoconjugates; Mice
PubMed: 33722856
DOI: 10.1158/1535-7163.MCT-20-0035 -
The Oncologist Sep 2015Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by... (Review)
Review
UNLABELLED
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by expert hematopathologists improves accuracy of subtyping, and referral to academic or specialty centers is recommended. Many patients, however, will receive treatment in the community, and knowledge of approved agents is key to optimizing therapeutic approaches for all patients. There is no current standard of care for patients with PTCL and no approved therapies for first-line treatment. Although many patients initially respond to induction chemotherapy, responses are often brief, and many patients relapse or become treatment refractory. For patients with relapsed or refractory PTCL, achievement of durable responses is challenging, and there are few treatment options. Romidepsin is a histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received one prior systemic therapy or more and patients with PTCL who have received one prior therapy or more. Approval of romidepsin for PTCL was based on a pivotal phase II study of patients with relapsed or refractory PTCL (n = 131) that demonstrated an objective response rate of 25% including 15% with complete response; responses lasted a median of >2 years. Long-term responses to romidepsin were achieved in patients regardless of baseline characteristics, including subtype, heavy pretreatment, response to prior therapy, or advanced disease. Common adverse events included hematologic abnormalities, gastrointestinal or asthenic conditions, and infections; romidepsin was not correlated with clinically meaningful QT prolongation or electrocardiogram abnormalities.
IMPLICATIONS FOR PRACTICE
Due to the rarity, severity, and heterogeneous nature of peripheral T-cell lymphoma (PTCL), diagnosis by expert hematopathologists is preferred, and referral to specialty centers is recommended. Many patients, however, will receive treatment in the community, and community oncologists play a key role in the recognition and treatment of PTCL. Knowledge of approved agents is key for optimizing therapeutic approaches. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.
Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Depsipeptides; Humans; Lymphoma, T-Cell, Peripheral; Prognosis; Treatment Outcome
PubMed: 26099743
DOI: 10.1634/theoncologist.2015-0043 -
Disease Markers 2015High recurrence rate is one representative characteristic of bladder cancer. Intravesical therapy after transurethral resection is often performed in patients with... (Review)
Review
High recurrence rate is one representative characteristic of bladder cancer. Intravesical therapy after transurethral resection is often performed in patients with nonmuscle invasive bladder cancer (NMIBC) to prevent recurrence. Bacillus Calmette-Guérin (BCG) and several anticancer/antibiotic agents, such as mitomycin C and epirubicin, are commonly used for this therapy. BCG treatment demonstrates strong anticancer effects. However, it is also characterized by a high frequency of adverse events. On the other hand, although intravesical therapies using other anticancer and antibiotic agents are relatively safe, their anticancer effects are lower than those obtained using BCG. Thus, the appropriate selection of agents for intravesical therapy is important to improve treatment outcomes and maintain the quality of life of patients with NMIBC. In this review, we discuss the predictive value of various histological and molecular markers for recurrence after intravesical therapy in patients with NMIBC.
Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Apoptosis; Biomarkers, Tumor; Humans; Recurrence; Urinary Bladder Neoplasms
PubMed: 26681820
DOI: 10.1155/2015/857416 -
Chemphyschem : a European Journal of... Aug 2018Mesoporous silica nanoparticles (MSNs) have been demonstrated to be one of the most promising drug-delivery systems (DDSs) to transport a variety of drugs/biomolecules.... (Review)
Review
Mesoporous silica nanoparticles (MSNs) have been demonstrated to be one of the most promising drug-delivery systems (DDSs) to transport a variety of drugs/biomolecules. Functionalization of MSN surfaces with responsive polymer brushes leads to intelligent and controllable drug-delivery properties, that is, the encapsulated drugs/biomolecules will only be released upon certain stimuli including pH, temperature, light, enzyme, ultrasound, or redox, thus maximizing their therapeutic efficiency and minimizing side effects. These polymer brushes can also increase the stability and extend the release period of the loaded cargoes. This Minireview presents an overview of recent research progress on stimuli-responsive controlled DDSs based on polymer-brush-grafted MSNs. Utilizing the switching abilities of the grafted responsive polymer brushes, the smart DDSs show great potential for biomedical applications, especially for cancer therapy.
Topics: Antibiotics, Antineoplastic; Cell Proliferation; Doxorubicin; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Particle Size; Polymers; Porosity; Silicon Dioxide; Surface Properties
PubMed: 29575338
DOI: 10.1002/cphc.201800018