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Saw, Phei Er,Park, Jinho,Jon, Sangyong,Farokhzad, Omid C. Elsevier 2017 NANOMEDICINE Vol.13 No.2
<P><B>Abstract</B></P> <P>A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APT<SUB>EDB</SUB>)-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APT<SUB>EDB</SUB>-LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APT<SUB>EDB</SUB>-LS(Dox) or APT<SUB>EDB</SUB>-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APT<SUB>EDB</SUB>-LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy.</P> <P><B>Graphical Abstract</B></P> <P>A novel multi-drug resistance cancer therapy – EDB targeting liposome simultaneously encapsulating MDR-1 siRNA and doxorubicin for targeted, co-delivery of drug for the treatment of drug resistant breast cancer.</P> <P>[DISPLAY OMISSION]</P>
Saw, Phei Er,Ko, Young Tag,Jon, Sangyong WILEY-VCH Verlag 2010 Macromolecular Rapid Communications Vol.31 No.13
<P>The effective use of oligonucleotide therapeutics, such as antisense oligodeoxynucleotides (ODNs) and small interfering RNAs (siRNAs), requires efficient delivery systems capable of intracellular penetration. Cell-penetrating peptides (CPPs), including arginine-rich peptides, have been extensively studied as tools for enhancing intracellular uptake efficiency of various bioactive molecules, including nanoparticles and liposomes. CPPs also have an ability to form tight complexes with nucleic acids, such as ODNs and siRNAs, making CPPs effective as packaging agents. Here, we constructed a CPP-modified liposome loaded with complexes of nona-arginine (9R) and NF-κB decoy ODNs, and evaluated intracellular uptake and anticancer activity in vitro. We found that 9R/ODN complexes were efficiently loaded into liposomes that were effectively internalized into U87MG glioblastoma cells and sensitized cells to the effects of paclitaxel. To the best of our knowledge, this is the first report describing the dual use of 9R CPP as a cell penetrating and a complexing agent within a single nanoparticle.</P><P> <img src='wiley_img_2010/10221336-2010-31-13-MARC200900861-gra001.gif' alt='wiley_img_2010/10221336-2010-31-13-MARC200900861-gra001'> </P> <B>Graphic Abstract</B> <P>A novel liposomal nanocarrier system composing oligoarginine (nonaarginine) as both complexation reagent and as cell penetrating peptide is presented. Nonaarginine, when complexed to oligonucleotide (ODN), greatly increase the encapsulation efficiency of ODN into the liposome (i.e., almost 100% encapsulation). When nonaargine is conjugated to the liposome, it functions as cell penetrating peptide that greatly enhances the uptake of our liposomal formulation in vitro. This 9R-LS holds great promise for a myriad of applications including higher loading of gene or drugs, enhanced cell transfection efficacy and can simultaneously used for tumor-specific targeted delivery in vivo. <img src='wiley_img_2010/10221336-2010-31-13-MARC200900861-content.gif' alt='wiley_img_2010/10221336-2010-31-13-MARC200900861-content'> </P>
Chong, Kyuha,Ku, Taeyun,Saw, Phei Er,Jon, Sangyong,Park, Ji-Ho,Choi, Chulhee The Royal Society of Chemistry 2013 Chemical communications Vol.49 No.98
<P>We engineered phototherapeutic sub-12 nm-sized polymeric micelles to treat malignant brain tumours (MBTs). The engineered nanoparticles in MBT cells enhanced the photocytotoxic efficiency more than 2.5-fold compared with parental and PEGylated photosensitisers (PSs). Increased subcellular co-localisation of PSs in mitochondria was observed.</P> <P>Graphic Abstract</P><P>We engineered phototherapeutic sub-12 nm-sized polymeric micelles which had enhancement of the photocytotoxic efficiency with increased co-localisation in mitochondria. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c3cc46166a'> </P>
HER2-specific aptide conjugated magneto-nanoclusters for potential breast cancer imaging and therapy
Park, Jinho,Park, Seho,Kim, Sunghyun,Lee, In-Hyun,Saw, Phei Er,Lee, Kwangyeol,Kim, Yong-Chul,Kim, Young-Joon,Farokhzad, Omid C.,Jeong, Yong Yeon,Jon, Sangyong The Royal Society of Chemistry 2013 Journal of materials chemistry. B, Materials for b Vol.1 No.36