SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy

Naumann, Jordan A.; Widen, John C.; Jonart, Leslie A.; Ebadi, Maryam; Tang, Jun‐Ming; Gordon, David; Harki, Daniel A.; Gordon, Peter M.

doi:10.1021/acs.bioconjchem.7b00774

Cited by 19 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interesting studies were carried by Naumann et al [ 120 ]. The team employed SN-38 conjugated to gold nanoparticles via oligonucleotides complementary to specific mRNAs unique to the cancer cells of Ewing sarcoma.…”

Section: New Irinotecan Formulationsmentioning

confidence: 99%

See 1 more Smart Citation

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Kciuk

Marciniak

Kontek

2020

IJMS

157

View full text Add to dashboard Cite

Irinotecan has been used in the treatment of various malignancies for many years. Still, the knowledge regarding this drug is expanding. The pharmacogenetics of the drug is the crucial component of response to irinotecan. Furthermore, new formulations of the drug are introduced in order to better deliver the drug and avoid potentially life-threatening side effects. Here, we give a comprehensive overview on irinotecan’s molecular mode of action, metabolism, pharmacogenetics, and toxicity. Moreover, this article features clinically used combinations of the drug with other anticancer agents and introduces novel formulations of drugs (e.g., liposomal formulations, dendrimers, and nanoparticles). It also outlines crucial mechanisms of tumor cells’ resistance to the active metabolite, ethyl-10-hydroxy-camptothecin (SN-38). We are sure that the article will constitute an important source of information for both new researchers in the field of irinotecan chemotherapy and professionals or clinicians who are interested in the topic.

show abstract

Section: New Irinotecan Formulationsmentioning

confidence: 99%

“…In a cancer cell, the SN38-conjugate oligonucleotide is released, allowing the inhibition of topoisomerase by SN-38. The obtained result showed that the drug was efficiently delivered and selectively released in both in vitro and in vivo conditions [ 120 ].…”

Section: New Irinotecan Formulationsmentioning

confidence: 99%

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Kciuk

Marciniak

Kontek

2020

IJMS

157

View full text Add to dashboard Cite

show abstract

“…Furthermore, the dimeric prodrugs could respond to the high glutathione (GSH) level of the tumor, to produce active monomeric drugs. SN38 is an active metabolite of camptothecin in vivo, and works on DNA topoisomerase for cancer cells killing . LND, a hexokinase inhibitor, exhibits antitumor activity by impacting energy metabolism .…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

Yang

Tong

et al. 2019

Adv Funct Materials

104

View full text Add to dashboard Cite

The application of combinational therapy makes up for the limitation of monotherapy and achieves superior treatment against cancer. However, the combinational therapy remains restricted by the poor tumor-specific delivery and the abscopal effect. Herein, reactive oxygen species (ROS)responsive PEGylated bilirubin nanoparticles (BRNPs) are developed to encapsulate two glutathione-activatable drugs, including dimer-7ethyl-10-hydroxycamptothecin (d-SN38) and dimer-lonidamine (d-LND). Dimerization of the drugs significantly increases the drug loading capacity and the encapsulation efficiency of nanoparticles. With the assistance of iRGD peptide (cRGDKGPDC), the cellular uptake of BRNPs is more than double when compared with the control. In response to high levels of intracellular ROS, d-SN38 and d-LND are rapidly released from nanoparticles (SL@BRNPs). Furthermore, the pharmacodynamic experiments verify combining SL@BRNPs with anti-PD-L1 antibody greatly inhibits the primary tumor of breast cancer, improves CD8+ T cells levels, and CD8+ T cells/Tregs ratios in the tumor. Additionally, it shows high immune memory effect and can prevent the growth of lung metastasis. Taken together, the strategy pioneers a new way for the rational design of nanoassemblies through the combination of activatable drug dimers and stimuli-responsive drug release, and a successful application of novel drug delivery systems in combination with the immune checkpoint blockade antibody.

show abstract

“…Gold nanoparticles have gained significant attention in recent years as nanocarriers due to their tunable size, flexibility of surface functionalization, and modifiable rate of cellular uptake which depend on the surface functionaliza- tion. 54,55) A recent study by Lee et al demonstrated HDR of the DMD-associated, C-X-C motif chemokine receptor 4 (CXCR4) gene using a gold nanoparticle-polymer complex. 56) This vehicle was composed of a 15 nm gold core conjugated with thiol-modified oligonucleotides and complexed with donor DNA.…”

Section: Non-viral Delivery Methodsmentioning

confidence: 99%

Advances in CRISPR/Cas9 Technology for in Vivo Translation

Çiçek

Luther

Kretzmann

et al. 2019

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has revolutionized therapeutic gene editing by providing researchers with a new method to study and cure diseases previously considered untreatable. While the full range and power of CRISPR technology for therapeutics is being elucidated through in vitro studies, translation to in vivo studies is slow. To date there is no totally effective delivery strategy to carry CRISPR components to the target site in vivo. The complexity of in vivo delivery is furthered by the number of potential delivery methods, the different forms in which CRISPR can be delivered as a therapeutic, and the disease target and tissue type in question. There are major challenges and limitations to delivery strategies, and it is imperative that future directions are guided by well-conducted studies that consider the full effect these variables have on the eventual outcome. In this review we will discuss the advances of the latest in vivo CRISPR/Cas9 delivery strategies and highlight the challenges yet to be overcome. Key words clustered regularly interspaced short palindromic repeat; genomics; therapeutics; in vivo CURRENT STRATEGIES IN CRISPR/CAS9 IN VIVO DELIVERYTherapeutic translatability of the CRISPR/Cas9 system requires that the various components of the system be delivered intracellularly, and with the desired localization in vivo. The CRISPR/Cas9 machinery can be introduced in multiple forms, Drug Discovery: Recent Progress and the FutureReview * Cas9 pDNA size is representative of full vector, spCas9 itself is 4.5 kilobase (kb) in size.

show abstract

SN-38 Conjugated Gold Nanoparticles Activated by Ewing Sarcoma Specific mRNAs Exhibit In Vitro and In Vivo Efficacy

Cited by 19 publications

References 38 publications

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

Tumor Microenvironment‐Responsive Dual Drug Dimer‐Loaded PEGylated Bilirubin Nanoparticles for Improved Drug Delivery and Enhanced Immune‐Chemotherapy of Breast Cancer

Advances in CRISPR/Cas9 Technology for <i>in Vivo</i> Translation

Contact Info

Product

Resources

About