A Reduction‐responsive Amphiphilic Methotrexate‐Podophyllotoxin Conjugate for Targeted Chemotherapy

Hou, Meili; S, Li; Xu, Zhigang; Li, Baosheng

doi:10.1002/asia.201901070

Cited by 19 publications

(11 citation statements)

References 34 publications

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“…To overcome these disadvantages, Hou and co-workers conjugated hydrophobic PPT and hydrophilic methotrexate (MTX) via a reduction-responsive disulfide bond. The nanoprodrug formulated by this amphiphilic drug conjugates the successfully improved tumor delivery of PPT [ 98 ]. Huang and co-workers synthesized an amphiphilic drug–drug conjugate from the hydrophilic anticancer drug irinotecan (Ir) and hydrophobic anticancer drug chloramphenicol (Cb) through hydrolyzable ester ligation.…”

Section: Categories Of Drug Conjugatesmentioning

confidence: 99%

Research Progress of Conjugated Nanomedicine for Cancer Treatment

Zhao

Chen

Hong³

et al. 2022

Pharmaceutics

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The conventional cancer therapeutic modalities include surgery, chemotherapy and radiotherapy. Although immunotherapy and targeted therapy are also widely used in cancer treatment, chemotherapy remains the cornerstone of tumor treatment. With the rapid development of nanotechnology, nanomedicine is believed to be an emerging field to further improve the efficacy of chemotherapy. Until now, there are more than 17 kinds of nanomedicine for cancer therapy approved globally. Thereinto, conjugated nanomedicine, as an important type of nanomedicine, can not only possess the targeted delivery of chemotherapeutics with great precision but also achieve controlled drug release to avoid adverse effects. Meanwhile, conjugated nanomedicine provides the platform for combining several different therapeutic approaches (chemotherapy, photothermal therapy, photodynamic therapy, thermodynamic therapy, immunotherapy, etc.) with the purpose of achieving synergistic effects during cancer treatment. Therefore, this review focuses on conjugated nanomedicine and its various applications in synergistic chemotherapy. Additionally, the further perspectives and challenges of the conjugated nanomedicine are also addressed, which clarifies the design direction of a new generation of conjugated nanomedicine and facilitates the translation of them from the bench to the bedside.

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Section: Categories Of Drug Conjugatesmentioning

confidence: 99%

Research Progress of Conjugated Nanomedicine for Cancer Treatment

Zhao

Chen

Hong³

et al. 2022

Pharmaceutics

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“…In addition, MTX was able to target folic acid overexpressing tumor cells. The results indicated that the nano-formulation could significantly enhance the biocompatibility and decrease the toxicity of PPT [22] . Thus, it should be simple, effective and promising strategy to construct the carrier-free DDSs based on ADDC for synergistic cancer therapy.…”

Section: Introductionmentioning

confidence: 95%

“…Aiming at these problems, a lot of research has been done to develop carrier-free drug self-delivery systems based on amphiphilic drug-drug conjugate (ADDC) [18] , [19] , [20] . ADDC is an amphiphilic molecule formed by connecting hydrophilic drugs and hydrophobic drugs through chemical bonds, which can self-assemble into nano-drugs by hydrophobic forces to realize drug self-delivery [21 , 22] . These carrier-free DDSs possess well-defined structures, precise drug ratios, high drug loading capacity and low-toxicity metabolic pathways [3 , 23 , 24] .…”

Section: Introductionmentioning

confidence: 99%

Carrier-free prodrug nanoparticles based on dasatinib and cisplatin for efficient antitumor in vivo

Xie

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Carrier-free drug self-delivery systems consisting of amphiphilic drug-drug conjugate (ADDC) with well-defined structure and nanoscale features have drawn much attention in tumor drug delivery. Herein, we report a simple and effective strategy to prepare ADDC using derivatives of cisplatin (CP) and dasatinib (DAS), which further self-assembled to form reduction-responsive nanoparticles (CP-DDA NPs). DAS was modified with succinic anhydride and then connected with CP derivative by ester bonds. The size, micromorphology and in vitro drug release of CP-DDA NPs were characterized. The biocompatibility and bioactivity of these carrier-free nanoparticles were then investigated by HepG2 cells and H22-tumor bearing mice. In vitro and in vivo experiments proved that CP-DDA NPs had excellent anti-tumor activity and significantly reduced toxicities. This study provides a new strategy to design the carrier-free nanomedicine composed of CP and DAS for synergistic tumor treatment.

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“…However, it is a proved fact that high dose of this antimetabolite involves parallel reactions in the human body leading to severe side effects like gastritis, nausea, hair loss, and abnormal liver function; hence these types of drugs required specific dosage based on the individual patient conditions and requires the administration of co-drugs like folic acid and folinic acid to avoid the side effects of methotrexate. [2][3][4][5] Another top marketed drug lenalidomide for the treatment of cancer is known to induce severe side effects like lowering the blood count, blood clot, and severe nerve damage. A. Toma et al have reported that continuous administration of lenalidomide may cause eosinophilic pneumonia due to adverse drug reactions.…”

Section: Introductionmentioning

confidence: 99%

“…Methotrexate (amethopterin) most popular and universally used drug to treat cancer, generally a high dosage of methotrexate with leucovorin is used to treat cancer. However, it is a proved fact that high dose of this antimetabolite involves parallel reactions in the human body leading to severe side effects like gastritis, nausea, hair loss, and abnormal liver function; hence these types of drugs required specific dosage based on the individual patient conditions and requires the administration of co‐drugs like folic acid and folinic acid to avoid the side effects of methotrexate [2–5] . Another top marketed drug lenalidomide for the treatment of cancer is known to induce severe side effects like lowering the blood count, blood clot, and severe nerve damage.…”

Section: Introductionmentioning

confidence: 99%

In Vitro, Molecular Docking, and In Silico Binding Mode Analysis of Organic Compounds for Antimicrobial and Anticancer Activity against Jurkat, HCT116, and A549 Cell Lines.

et al. 2020

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A set of four novel organic molecules bearing hydrazide, azomethine, and sulfonamide linkages were synthesized by a condensation reaction, and characterized using ubiquitous spectroscopic techniques. The synthesized molecules were screened against Jurkat, HCT116, and A549 cell lines for their in‐vitro cytotoxic activity, antimicrobial activity and were found to be promising as anticancer and antimicrobial agents. Among four molecules, pyridine‐hydroxynaphalene based molecule (R3) showed comprehensive anticancer activity towards all three cancer cell lines. On the other hand, R1, R2, and R4 were found to be moderate antimicrobial agents. The mode of action for anticancer activity and antimicrobial activity was further supported by molecular docking studies of the potent compounds against the enzyme Methinonyl‐TRNA Synthetase (PDB ID:1PG2), bacterial DNA Gyrase B (PDB ID:3G75), and yeast GTPase (PDB ID:3 A58). Further, Molecular dynamics (MD) simulations studies were analyzed to study the stability of the ligand‐protein complex.

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A Reduction‐responsive Amphiphilic Methotrexate‐Podophyllotoxin Conjugate for Targeted Chemotherapy

Cited by 19 publications

References 34 publications

Research Progress of Conjugated Nanomedicine for Cancer Treatment

Research Progress of Conjugated Nanomedicine for Cancer Treatment

Carrier-free prodrug nanoparticles based on dasatinib and cisplatin for efficient antitumor in vivo

In Vitro, Molecular Docking, and In Silico Binding Mode Analysis of Organic Compounds for Antimicrobial and Anticancer Activity against Jurkat, HCT116, and A549 Cell Lines.

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