Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells

Chi, Lianhua; Na, Moon Hee; Jung, Hyun Hwan; Vadevoo, Sri Murugan Poongkavithai; Kim, Cheong Wun; Padmanaban, Guruprasath; Park, Tae In; Park, Jae Yong; Hwang, Ilseon; Park, Keon Uk; Liang, Frank; Lu, Maggie; Park, Ji-Ho; Kim, In San; Lee, Byung Heon

doi:10.1016/j.jconrel.2015.05.260

Cited by 44 publications

(37 citation statements)

References 36 publications

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“…In addition, we showed that IL4RPep-1 could bind to both mouse and human tumor cells that highly express IL4R. As previously described by us and other groups (21,26,47,50), three arginine residues on IL4RPep-1 (CRKRLDRNC) are homologous to those residues on human IL4 ( 81 RFLKRLDRNLW 91 ) and mouse IL4 ( 79 QRLFRAFR 86 ). This may explain the cross-species specificity of IL4RPep-1 binding.…”

Section: Discussionsupporting

confidence: 70%

“…Type I is composed of IL4Ra and common g-chain and is expressed on the surface of cells of hematopoietic stem cell origin (16,17). Type II comprises IL4Ra and IL13Ra chains and is expressed on the surface of cells of nonhematopoietic stem cell origin, such as tumor cells, including breast cancer and lung cancer cells (18)(19)(20)(21). Of interest, M2polarized macrophages express higher levels of IL4R than M1-polarized macrophages (7,8,15).…”

Section: Introductionmentioning

confidence: 99%

“…We previously identified IL4RPep-1, a 9-mer peptide with the sequence CRKRLDRNC, which is homologous to the sequence of IL4, via screening of a phage-displayed peptide library (26). We previously suggested the possibility that IL4RPep-1 could specifically bind to IL4R (26) and selectively target IL4R-expressing tumors (21,27). The amphiphilic proapoptotic peptide (KLAKLAK) 2 is known to trigger mitochondrial membrane disruption and release of cytochrome c, which subsequently induces apoptotic cell death (28,29).…”

Section: Introductionmentioning

confidence: 99%

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IL4 Receptor–Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity

Vadevoo

Kim

Gunassekaran

et al. 2017

Molecular Cancer Therapeutics

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Cellular cross-talk between tumors and M2-polarized tumor-associated macrophages (TAM) favors tumor progression. Upregulation of IL4 receptor (IL4R) is observed in diverse tumors and TAMs. We tested whether an IL4R-targeted proapoptotic peptide could inhibit tumor progression. The IL4R-binding peptide (IL4RPep-1) preferentially bound to IL4R-expressing tumor cells and M2-polarized macrophages both and in 4T1 breast tumors To selectively kill IL4R-expressing cells, we designed an IL4R-targeted proapoptotic peptide, IL4RPep-1-K, by adding the proapoptotic peptide (KLAKLAK) to the end of IL4RPep-1. IL4RPep-1-K exerted selective cytotoxicity against diverse IL4R-expressing tumor cells and M2-polarized macrophages. Systemic administration of IL4RPep-1-K inhibited tumor growth and metastasis in 4T1 breast tumor-bearing mice. Interestingly, IL4RPep-1-K treatment increased the number of activated cytotoxic CD8 T cells while reducing the numbers of immunosuppressive regulatory T cells and M2-polarized TAMs. No significant systemic side effects were observed. These results suggest that IL4R-targeted proapoptotic peptide has potential for treating diverse IL4R-expressing cancers. .

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IL4 Receptor–Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity

Vadevoo

Kim

Gunassekaran

et al. 2017

Molecular Cancer Therapeutics

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“…3) (37,38). EPC (0.1–0.4%), cholesterol (0.03–0.20%) and SG (0.04%) were dissolved in 2 ml absolute ethanol.…”

Section: Methodsmentioning

confidence: 99%

Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate

et al. 2018

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In the current study, norcantharidin (NCTD)-loaded liposomes (LIPs) modified with stearyl glycyrrhetinate (SG; SG-NCTD-LIP) were prepared by the ethanol injection method. To increase the drug encapsulation efficiency (EE), the formulation of NCTD-LIP was optimized by single factor test and orthogonal design. The release of NCTD in vitro from SG-NCTD-LIP was evaluated by equilibrium dialysis. The cytotoxicity of SG-NCTD-LIP in HepG2 was investigated by MTT assay. The results revealed that the EE of liposomes was ~27.80%, the average SG-NCTD-LIP was 87.5 nm, the in vitro NCTD release from SG-NCTD-LIP was delayed compared with NCTD in solution and the drug-release kinetic followed a first-order model. MTT assays revealed increased cytotoxicity activity against HepG2 cells for SG-NCTD-LIP compared with free NCTD. In conclusion, SG-NCTD-LIP prepared in the present study may be a promising liposomal drug delivery system for anticancer drugs in liver-targeting therapy.

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“…Peptides are suitable for deep tissue penetration due to their small size and are easy to be chemically conjugated with therapeutic drugs and imaging agents (10,11). These features enable them to be useful tumor-homing probes for targeted drug delivery and in vivo imaging of cancer (12)(13)(14). Many tumor-homing peptides have been identified by phage display (15,16).…”

Section: Introductionmentioning

confidence: 99%

A Peptide Probe Enables Photoacoustic-Guided Imaging and Drug Delivery to Lung Tumors in K-rasLA2 Mutant Mice

et al. 2019

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The lack of molecular targets and targeting probes remains a major drawback for targeted imaging and drug delivery in lung cancer. In this study, we exploited in vivo phage display to identify a novel targeting probe that homes to the tumor in a K-ras LA2 mutant mouse lung cancer model. Compared with other candidate peptides selected from 5 rounds of phage display, the CRQTKN peptide homed to tumor nodules in the lung of mutant mice at higher levels. Photoacoustic tomography of mutant mice detected lung tumors via tumor homing of the near-infrared fluorescence dye-labeled CRQTKN peptide. Ex vivo photoacoustic images of isolated organs further demonstrated tumor homing of the CRQTKN peptide, whereas minimal accumulation was observed in control organs, such as the liver. Compared with untargeted liposomes and doxorubicin, doxorubicin-loaded liposomes whose surface was modified with the CRQTKN peptide more efficiently delivered doxorubicin and reduced the number or size of tumor lesions in K-ras LA2 mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinitybased identification was used to detect TNF receptor superfamily member 19L (TNFRSF19L), which was upregulated in lung tumors of mutant mice, as the receptor for the CRQTKN peptide. In conclusion, these results suggest that the CRQTKN peptide is a promising targeting probe for photoacousticguided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L. Significance: These findings present a new tumor-targeting probe for photoacoustic-guided detection and drug delivery.

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Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells

Cited by 44 publications

References 36 publications

IL4 Receptor–Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity

IL4 Receptor–Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity

Preparation and characterization of norcantharidin liposomes modified with stearyl glycyrrhetinate

A Peptide Probe Enables Photoacoustic-Guided Imaging and Drug Delivery to Lung Tumors in K-rasLA2 Mutant Mice

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