Ligand peptide-grafted PEGylated liposomes using HER2 targeted peptide-lipid derivatives for targeted delivery in breast cancer cells: The effect of serine-glycine repeated peptides as a spacer

Suga, Tadaharu; Fuchigami, Yuki; Hagimori, Masayori; Kawakami, Shigeru

doi:10.1016/j.ijpharm.2017.02.041

Cited by 39 publications

(38 citation statements)

References 13 publications

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“…To deliver nanoparticles to specific tissues and cells, ligand modification is a rational strategy. Recently, we have reported high functionality and quality (HFQ) lipids for the preparation of ligand-targeted PEGylated liposomes and demonstrated the advantage of using a serine-glycine repeats (SG)5 spacer for efficient peptide ligand presentation on the liposomal surface [22]. This technique is simple and versatile because HFQ lipids are post-inserted into the 6 liposomes.…”

Section: Introductionmentioning

confidence: 99%

Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

Peng

Fumoto

Suga

et al. 2019

Journal of Controlled Release

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Synchronized bio-distribution of combination therapies has several merits such as synergistic effects and reduced side-effects. Co-delivery of a protein and small molecule drug using a single nanocarrier is challenging because they possess totally different characteristics. Herein, we report the development of sophisticated nanoparticles composed of lipids, calcium carbonate and RGD peptide ligands for the co-delivery of a protein and small molecule drug combination via a simple preparation method. A 'one-step' ethanol injection method was employed to prepare the highly organized nanoparticles. The nanoparticles exhibited a spherical shape with ca. 130 nm diameter, and clearly had an integrated lipid layer covering the periphery. As a ligand, an RGDmodified lipid was post-inserted into the nanoparticles, which was important to overcome the 'PEG dilemma'. The pH-sensitivity of the targeted nanoparticles contributed to the efficient intracellular co-delivery of a protein and drug combination in Colon26 tumor cells, and noticeably improved their accumulation in the tumor region of xenograft mice. Synchronized bio-distribution of the protein and drug was achieved, which was the foundation for the synergistic effects of the combination. The targeting capability of the nanoparticles along with their pH-sensitive drug release and the synchronized bio-distribution of their cargos led to the significant antitumor activity of the SOD and paclitaxel combination in mice. This study provides novel information for the design and preparation of functionalized nanoparticles for the delivery of a protein/drug combination in vivo.

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Section: Introductionmentioning

confidence: 99%

Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

Peng

Fumoto

Suga

et al. 2019

Journal of Controlled Release

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“…The KWSY sequence was, in this study, modified from KCCYSL, a well-known ErbB2-targeting motif. KCCYSL was identified as an ErbB2-binding peptide through phage-display screening [25], and was used for cancer imaging agents and delivery tools to target ErbB2-expressing cells [10][11][12]26]. In this study, direct coupling of KCCYSL with the MTD was not satisfactory because high amounts of KCCYSL:MTD were needed to kill the ErbB2-high-expressing FaDu cells.…”

Section: Discussionmentioning

confidence: 99%

Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2‐targeting moieties

et al. 2017

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Many anticancer drugs target epidermal growth factor receptors to inhibit receptor tyrosine kinases and tumor growth. Here, we show that an ErbB2‐targeting pronecrotic peptide (KWSY:MTD) selectively kills tumor cells expressing ErbB2 in vitro. An antibody against ErbB2 inhibits KWSY:MTD‐induced cell death. KWSY:MTD causes membrane permeability which allows propidium iodide entry into the cytosol and the release of HMGB1 into the media, indicative of necrosis. Mitochondrial swelling occurs in response to KWSY:MTD. Moreover, in vivo analysis using a mouse model shows that KWSY:MTD partially suppressed growth in tumor tissue bearing ErbB2‐expressing cells, but did not have obvious toxicity in mouse liver or kidney tissue. Taken together, KWSY:MTD has potential as an ErbB2‐targeting anticancer drug.

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“…In addition, we compared the uptake pathways taken by various Rn and NuBCP-9-Rn conjugates in a Bcl-2 overexpressing cell line, MDA-MB-231 (human breast cancer cells). 17,18) We found that NuBCP-9-R12 and NuBCP-9-R14 conjugates resulted in severe non-specific cytotoxicity. Based on our results, NuBCP-9-R10 conjugate was concluded to be a good compound for inducing apoptosis through Bcl-2 in cancer cells while resulting in a tolerable degree of non-specific cytotoxicity.…”

mentioning

confidence: 89%

Investigation of Intracellular Delivery of NuBCP-9 by Conjugation with Oligoarginines Peptides in MDA-MB-231 Cells

Wang

Suga

Hagimori

et al. 2018

Biological & Pharmaceutical Bulletin

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Oligoarginines (Rn) are becoming promising tools for the intracellular delivery of biologically active molecules. NuBCP-9, a peptide that induces apoptosis in B-cell lymphoma 2 (Bcl-2)-expressing cancer cells, has been reported to promote the uptake and non-specific cytotoxicity of R8, also called octaarginine. However, it is unknown whether a similar synergistic effect can be seen with other Rn. In this study, we conjugated NuBCP-9 with various Rn (n=8, 10, 12, 14) to investigate and compare their cellular uptake characteristics. In addition, their non-specific cytotoxicity and apoptosis-inducing abilities were evaluated. We found that NuBCP-9 conjugated with Rn enhanced cellular uptake mainly through clathrin-mediated endocytosis and macropinocytosis, and that the uptake pathways were not different from those used by unconjugated Rn. However, the cytotoxicity study showed that NuBCP-9-R12 and NuBCP-9-R14 conjugates enhanced non-specific cytotoxicity. We found that NuBCP-9-R10 conjugate had the highest uptake efficiency and induced correspondingly high levels of apoptosis, while resulting in a tolerable degree of non-specific toxicity.

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Ligand peptide-grafted PEGylated liposomes using HER2 targeted peptide-lipid derivatives for targeted delivery in breast cancer cells: The effect of serine-glycine repeated peptides as a spacer

Cited by 39 publications

References 13 publications

Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

Targeted co-delivery of protein and drug to a tumor in vivo by sophisticated RGD-modified lipid-calcium carbonate nanoparticles

Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2‐targeting moieties

Investigation of Intracellular Delivery of NuBCP-9 by Conjugation with Oligoarginines Peptides in MDA-MB-231 Cells

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