Synergistic action of doxorubicin and 7-Ethyl-10-hydroxycamptothecin polyphosphorylcholine polymer prodrug

Wu, Zhengzhong; Li, Shuai; Cai, Yuanyuan; chen, Fan; Chen, Yuanwei; Luο, Xingguang

doi:10.1016/j.colsurfb.2019.110741

Cited by 15 publications

(5 citation statements)

References 37 publications

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“…[14][15][16] However, as a small molecule cytotoxic drug, SN38 has a poor targeting ability, which can not only kill tumor cells, but also cause serious damage to normal cells and tissues, showing enormous side effects, such as bone marrow transplantation, hair loss, delayed diarrhea, etc., seriously limiting the improvement of drug dose. 14,17,18 In addition, SN38 is a neutral alkaloid insoluble in acid and water and has very low solubility in various solvents currently available for pharmaceutical preparations, so it is difficult to be administered intravenously. 19 The nanoparticle drug delivery system (Nano-DDS) shows promise to alleviate these limitations, which can improve the solubility of the drug.…”

Section: Introductionmentioning

confidence: 99%

Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment

Liu,

Xu,

Wang

et al. 2024

Biomater. Sci.

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Section: Introductionmentioning

confidence: 99%

Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment

Liu,

Xu,

Wang

et al. 2024

Biomater. Sci.

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“…values. As a result, only compounds 3 a and 3 b were chosen to examine the combination effects with doxorubicin [55][56][57][58] on breast cancer cells.…”

Section: Chemistryselectmentioning

confidence: 99%

“…But the other compounds did not exhibit appreciable IC 50 values. As a result, only compounds 3 a and 3 b were chosen to examine the combination effects with doxorubicin [55–58] on breast cancer cells.…”

Section: Biological Evaluationmentioning

confidence: 99%

N, N’‐Disubstituted Benzimidazolium Salts: Synthesis, Characterization, Micromolar Detection of Fe(III) ions in Aqueous system, Biological Evaluation and Molecular Docking Studies

et al. 2022

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A series of dicationic N, N’‐disubstituted benzimidazolium salts with Br− and PF6− as the counter anions were synthesized in 75–98 % yields. The single crystal X‐ray diffraction studies of one of the benzimidazolium salts confirmed the structure of these dicationic compounds. These salts exhibited a selective “turn‐off” fluorescence response toward Fe3+ ions in aqueous solution over the other competitive metal ions such as Ag+, Al3+, Ba2+, Ca2+, Co2+, Cr3+, Cu2+, Fe2+, K+, Mg2+, Na+, Ni2+, Pb2+, and Zn2+. Upon addition of 5 equivalents Fe3+ ions, emission intensity was quenched by 94–99 % in pure aqueous media. Detection limits for all probes with Fe3+ ions were found in micromolar range. Further, drug combination analysis was conducted by evaluating the combinatorial treatment effects of two benzimidazolium salts with doxorubicin on breast cancer cells using the Chou‐Talalay method and the Highest Single Agent (HSA) model, and it was found that these compounds showed synergism with doxorubicin. Further, molecular docking studies revealed the best docking score (−6.11) for one of the benzimidazolium salts, and explained its binding affinity with checkpoint kinase 2 (chk2) protein.

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“…Cathepsin B is overexpressed in various tumor types, including glioblastoma cells. , The valine-alanine (VA) dipeptide is a cathepsin B recognition sequence that has demonstrated stability in serum, and conjugates containing the sequence are stable in plasma until it accumulates in the tumor where cathepsin B is overexpressed . The protease recognizes and binds to the VA sequence, initiating a chemical reaction that leads to the cleavage of the linker after alanine. , The cleavage of the VA linker results in the release of the drug molecule from the conjugate. This allows the drug to become active and exert its therapeutic effects at the intended site of action.…”

Section: Introductionmentioning

confidence: 99%

“… 35 The protease recognizes and binds to the VA sequence, initiating a chemical reaction that leads to the cleavage of the linker after alanine. 36 , 37 The cleavage of the VA linker results in the release of the drug molecule from the conjugate. This allows the drug to become active and exert its therapeutic effects at the intended site of action.…”

Section: Introductionmentioning

confidence: 99%

Development of a Targeted SN-38-Conjugate for the Treatment of Glioblastoma

Bataille Backer,

Adekiya,

Kim

et al. 2024

ACS Omega

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Glioblastoma (GBM) is the most aggressive and fatal brain tumor, with approximately 10,000 people diagnosed every year in the United States alone. The typical survival period for individuals with glioblastoma ranges from 12 to 18 months, with significant recurrence rates. Common therapeutic modalities for brain tumors are chemotherapy and radiotherapy. The main challenges with chemotherapy for the treatment of glioblastoma are high toxicity, poor selectivity, and limited accumulation of therapeutic anticancer agents in brain tumors as a result of the presence of the blood−brain barrier. To overcome these challenges, researchers have explored strategies involving the combination of targeting peptides possessing a specific affinity for overexpressed cell-surface receptors with conventional chemotherapy agents via the prodrug approach. This approach results in the creation of peptide drug conjugates (PDCs), which facilitate traversal across the blood−brain barrier (BBB), enable preferential accumulation of chemotherapy within the neoplastic microenvironment, and selectively target cancerous cells. This approach increases accumulation in tumors, thereby improving therapeutic efficiency and minimizing toxicity. Leveraging the affinity of the HAIYPRH (T7) peptide for the transferrin receptor (TfR) overexpressed on the blood−brain barrier and glioma cells, a novel T7-SN-38 peptide drug conjugate was developed. The T7-SN-38 peptide drug conjugate demonstrates about a 2-fold reduction in glide score (binding affinity) compared to T7 while maintaining a comparable orientation within the TfR target site using Schrodinger-2022−3 Maestro 13.3 for ligand preparation and Glide SP-Peptide docking. Additionally, SN-38 extends into a solvent-accessible region, enhancing its susceptibility to protease hydrolysis at the cathepsin B (Cat B) cleavable site. The SN-38-ether-peptide drug conjugate displayed high stability in buffer at physiological pH, and cleavage of the conjugate to release free cytotoxic SN-38 was observed in the presence of exogenous cathepsin B. The synthesized peptide drug conjugate exhibited potent cytotoxic activities in cellular models of glioblastoma in vitro. In addition, blocking transferrin receptors using the free T7 peptide resulted in a notable inhibition of cytotoxicity of the conjugate, which was reversed when exogenous cathepsin B was added to cells. This work demonstrates the potential for targeted drug delivery to the brain in the treatment of glioblastoma using the transferrin receptor-targeted T7-SN-38 conjugate.

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Synergistic action of doxorubicin and 7-Ethyl-10-hydroxycamptothecin polyphosphorylcholine polymer prodrug

Cited by 15 publications

References 37 publications

Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment

Hindering the unlimited proliferation of tumor cells synergizes with destroying tumor blood vessels for effective cancer treatment

N, N’‐Disubstituted Benzimidazolium Salts: Synthesis, Characterization, Micromolar Detection of Fe(III) ions in Aqueous system, Biological Evaluation and Molecular Docking Studies

Development of a Targeted SN-38-Conjugate for the Treatment of Glioblastoma

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