Tumor accumulation of ε-poly-lysines-based polyamines conjugated with boron clusters

Umano, Masayuki; Uechi, Kazuhiro; Uriuda, Takatoshi; Murayama, Sayuri; Azuma, Hideki; Shinohara, Atsuko; Liu, Young; Ono, Koji; Kirihata, Mitsunori; Yanagië, Hironobu; Nagasaki, Takeshi

doi:10.1016/j.apradiso.2011.02.048

Cited by 15 publications

(9 citation statements)

References 7 publications

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“…We used polyethylene glycol (PEG) and poly-l-lysine (PLL) for manufacturing the AV, CR, and AVCR NPs. Poly-l-lysine (PLL) has an advantage of being hydro-and bio-degradable, and biocompatible (Umano et al, 2011), and so it is suitable as a drug delivery carrier. It has been reported that PLL-modified poly (lactic-co-glycolic acid) (PLGA) NPs showed significantly higher entrapment efficiency (EE%) than PLGA NPs (Tahara et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

Abdrabou

Ahmed

2019

Asian Pac J Cancer Prev

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Non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC) are very common in certain population around the world. Despite the recent advances in their diagnosis and therapy, their prognosis remains poor due to the development resistance to drug. Although doxorubicin (DOX) is considered to be one of the most anti-solid tumor drugs, developed resistance is contributing to unsuccessful outcome. The rationale of the current study is to explore the sensitizing capability of the DOX-treated cancer cells using the anticancer agents; bevacizumab (avastin; AV) and CCR2 inhibitor (CR) in their free-and nano-formulations. Here, the average size, polydispersity index (PDI), zeta potential, and entrpment effeciency (EE%) of the synthesized nanoparticles were measured. We investigated the effect of these platforms on the proliferation, apoptosis, necrosis, nitric oxide (NO), malondialdehyde (MDA), and zinc levels of human HCC (HepG2 and Huh-7) and NSCLC (A549) cancer cell lines. Glucose consumption rates using Huh-7 and A549 cancer cells were tested upon treatments. We demonstrated that AV and CR nano-treatments significantly suppressed A549 cell viability and activated apoptosis by NO level elevation. We concluded that AVCR NP plus DOX significantly induces A549 cytotoxicity-mediated apoptosis more than Huh-7 and HepG2 cells. This drug-drug nano-combination induced Huh-7 cytotoxicity-mediated apoptosis more than HepG2 cells. In conclusion, AVCR NP sensitized DOX-treated A549 and Huh-7 cells through reactive oxygen species (ROS)-stimulated apoptosis. Taken together, our data suggested that the CR plus AV nano-platforms would be a potential personalized medicine-based strategy for treating CCR2-positive NSCLC and HCC patients in the near future.

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Section: Discussionmentioning

confidence: 99%

Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

Abdrabou

Ahmed

2019

Asian Pac J Cancer Prev

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“…The first strategy involves the incorporation of boron into biomolecules with tumor-targeting abilities such as peptides and proteins, nucleic acids, carbohydrates, and porphyrins, 132,133 while the second approach uses liposomes and nanoparticles to deliver 10 B atoms to tumor tissues. 133–137 In particular, many boron-encapsulated and boron-lipid liposomes have shown promising results in their ability to selectively deliver therapeutic quantities of 10 B atoms into tumor cells for effective BNCT. 138–146 …”

Section: Biological Applicationsmentioning

confidence: 99%

Synthesis and Applications of Perfunctionalized Boron Clusters

et al. 2018

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This Viewpoint Article describes major advances pertaining to perfunctionalized boron clusters in synthesis and their respective applications. The first portion of this work highlights key synthetic methods allowing one to access a wide range of polyhedral boranes (B4 and B6 – B12 cluster cores) that contain exhaustively functionalized vertices. The second portion of this Viewpoint showcases the historical developments in using these molecules for applications ranging from materials science to medicine. Lastly, we suggest potential new directions for these clusters as they apply to both synthetic methods and applications.

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“…7 Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric NPs, and it has been approved by the Food and Drug Administration for drug delivery and has been frequently used. 8 Poly-l-lysine (PLL) has an advantage of being water soluble, hydrodegradable, biodegradable, and biocompatible, 9 and so it is suitable for the backbone as a drug delivery carrier. Recently, it has been reported that PLL-modified PLGA NPs showed significantly higher amounts than unmodified PLGA NPs.…”

Section: Introductionmentioning

confidence: 99%

PLGA-PLL-Peg-Tf-Based Targeted Nanoparticles Drug Delivery System Enhance Antitumor Efficacy Via Intrinsic Apoptosis Pathway

Wen

Liu

Chen

et al. 2015

Blood

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Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-L-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool. Disclosures No relevant conflicts of interest to declare.

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Tumor accumulation of ε-poly-lysines-based polyamines conjugated with boron clusters

Cited by 15 publications

References 7 publications

Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

Bevacizumab and CCR2 Inhibitor Nanoparticles Induce Cytotoxicity-Mediated Apoptosis in Doxorubicin-Treated Hepatic and Non-Small Lung Cancer Cells

Synthesis and Applications of Perfunctionalized Boron Clusters

PLGA-PLL-Peg-Tf-Based Targeted Nanoparticles Drug Delivery System Enhance Antitumor Efficacy Via Intrinsic Apoptosis Pathway

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