A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

Han, Leiqiang; Wang, Tianqi; Wu, Jingliang; Yin, Xiaolan; Fang, Hao; Zhang, Na

doi:10.2147/ijn.s118727

Cited by 29 publications

(14 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the top ten most signi cant potential small-molecule drugs, vorinostat and thalidomide were particularly interesting and have anti-tumor effects in NPC treatment. Vorinostat is a histone deacetylase inhibitors (HDACi), which has shown strong anti-tumor effects in various types of solid cancers, when combined with other traditional chemotherapeutic drugs like camptothecin and gemcitabine [44][45][46][47][48][49]. Thalidomide, is a glutamic acid derivative, which was a classic drug with immunemodulatory properties and tumor necrosis factor alpha inhibits [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

Liu

2020

Preprint

View full text Add to dashboard Cite

Background Nasopharyngeal carcinoma (NPC) is a heterogeneous carcinoma that the underlying molecular mechanisms involved in the tumor initiation, progression, and migration are largely unclear. The purpose of the present study was to identify key biomarkers and small-molecule drugs for NPC screening, diagnosis, and therapy via gene expression profile analysis. Methods Raw microarray data of NPC were retrieved from the Gene Expression Omnibus (GEO) database and analyzed to screen out the potential differentially expressed genes (DEGs). The key modules associated with histology grade and tumor stage was identified by using weighted correlation network analysis (WGCNA). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes in the key module were performed to identify potential mechanisms. Candidate hub genes were obtained, which based on the criteria of module membership (MM) and high connectivity. Then we used receiver operating characteristic (ROC) curve to evaluate the diagnostic value of hub genes. The Connectivity map database was further used to screen out small-molecule drugs of hub genes. Results A total of 430 DEGs were identified based on two GEO datasets. The green gene module was considered as key module for the tumor stage of NPC via WGCNA analysis. The results of functional enrichment analysis revealed that genes in the green module were enriched in regulation of cell cycle, p53 signaling pathway, cell part morphogenesis. Furthermore, four DEGs-related hub genes in the green module were considered as the final hub genes. Then ROC revealed that the final four hub genes presented with high areas under the curve, suggesting these hub genes may be diagnostic biomarkers for NPC. Meanwhile, we screened out several small-molecule drugs that have provided potentially therapeutic goals for NPC. Conclusions Our research identified four potential prognostic biomarkers and several candidate small-molecule drugs for NPC, which may contribute to the new insights for NPC therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

Liu

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, the benefit obtained compared to vorinostat alone was significant but modest and the subcutaneous administration route at the proximity of the tumor was not optimal for clinical transfer. The modest benefit of vorinostat vectorization in vivo on tumor growth, compared to the free molecule, was also observed in two additional studies using SAHA-loaded poly(ethylene glycol)-block-poly(caprolactone) (PEG-PCL) micelles [22] or using a self-assembly of a redox sensitive SAHA prodrug functionalized with a d-a-tocopheryl polyethylene glycol succinate [23].…”

Section: Concepts For Delivery Of Epigenetic Modulatorsmentioning

confidence: 92%

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

2019

View full text Add to dashboard Cite

Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.

show abstract

“…Meanwhile, our group also designed a series of SMND systems that exhibited excellent application potential. 21,22 Furthermore, we reported the concept of complex SMNDs, in which 5-fluorouracil and vorinostat were conjugated to the same molecular chain to unify their physicochemical properties. These prodrugs could self-assemble into complex SMNDs with precise and tunable drug ratios for combination therapy.…”

Section: Introductionmentioning

confidence: 99%

“…24 Recent studies have shown that Aes has an inhibitory effect against different tumors. [25][26][27] More importantly, based on our experience in designing self-assembled small molecules, 21,22 Aes acts as a stabilizer since it is amphiphilic.…”

Section: Introductionmentioning

confidence: 99%

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

Zheng

Wang

et al. 2020

IJN

Self Cite

View full text Add to dashboard Cite

Background: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. Materials and Methods: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. Results: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg −1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. Conclusion: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.

show abstract

A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

Cited by 29 publications

References 54 publications

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

Identification of Four Key Biomarkers and Small Molecule Drugs Innasopharyngeal Carcinoma by Weighted Gene Co-expression Network Analysis

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

Contact Info

Product

Resources

About