Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles

Kim, Myung Goo; Jo, Sung Duk; Yhee, Ji Young; Lee, Beom Suk; Lee, So Jin; Park, Sung Gurl; Kang, Sung Soo; Kim, Sun Hwa; Jeong, Ji Hoon

doi:10.1016/j.bbrc.2017.05.103

Cited by 28 publications

(19 citation statements)

References 22 publications

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“…Thus, any new therapeutic strategy to target this disease is of significant benefit. Small interference RNA (siRNA) is a promising therapeutic approach due to its ability to potentially knock down disease-related genes, and it has been intensively investigated for the treatment of a broad range of disorders [3,4,5,6,7]. In the case of glioblastoma treatment, it was recently shown by various groups that siRNA can successfully induce glioma-related gene knockdown and tumor growth inhibition within in vitro as well as in vivo experiments [8,9,10].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells

et al. 2019

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Glioblastoma multiforme is a devastating disease that has attracted enormous attention due to poor prognosis and high recurrence. Small interfering RNA (siRNA) in principle offers a promising therapeutic approach by the downregulation of disease-related genes via RNA interference. For efficient siRNA delivery to target sites, cationic polymers are often used in preclinical studies for the protection of siRNA and complex formation based on electrostatic interactions. In an effort to develop biocompatible and efficient nanocarriers with a translational outlook for optimal gene silencing at reduced toxicity, we synthesized two sets of nylon-3 copolymers with variable cationic content (DM or NM monomer) and hydrophobic subunits (CP monomer) and evaluated their suitability for in vitro siRNA delivery into glioblastoma cells. DM0.4/CP0.6 and NM0.4/CP0.6 polymers with similar subunit ratios were synthesized to compare the effect of different cationic subunits. Additionally, we utilized NM0.2/CP0.8 polymers to evaluate the impact of the different hydrophobic content in the polymer chain. The siRNA condensation ability and polymer–siRNA complex stability was evaluated by unmodified and modified SYBR gold assays, respectively. Further physicochemical characteristics, e.g., particle size and surface charge, were evaluated by dynamic light scattering and laser Doppler anemometry, whereas a relatively new method for polyplex size distribution analysis—tunable resistive pulse sensing—was additionally developed and compared to DLS measurements. Transfection efficiencies, the route of cell internalization, and protein knockdown abilities in glioblastoma cells were investigated by flow cytometry. Furthermore, cellular tolerability was evaluated by MTT and LDH assays. All the polymers efficiently condensed siRNA at N/P ratios of three, whereas polymers with NM cationic subunits demonstrated smaller particle size and lower polyplex stability. Furthermore, NM0.2/CP0.8 polyplexes with the highest hydrophobic content displayed significantly higher cellular internalization in comparison to more cationic formulations and successful knockdown capabilities. Detailed investigations of the cellular uptake route demonstrated that these polyplexes mainly follow clathrin-mediated endocytotic uptake mechanisms, implying high interaction capacity with cellular membranes. Taken together with conducive toxicity profiles, highly hydrophobic nylon-3 polymers provide an appropriate siRNA delivery agent for the potential treatment of glioblastoma.

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Section: Introductionmentioning

confidence: 99%

The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells

et al. 2019

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“…The co-delivery of antiangiogenesis drugs and gene silencing agents is considered to be another efficient way for cancer starvation therapy 43, 65-67. For example, Lima and coworkers synthesized a chlorotoxin (CTX)-conjugated liposomes for anti-miR-21 oligonucleotides delivery, which promoted the efficiency of miR-21 silencing and enhanced the antitumor activity with less systemic immunogenicity 68.…”

Section: Nanomedicine-mediated Cancer Starvation Therapymentioning

confidence: 99%

Advances in nanomedicine for cancer starvation therapy

et al. 2019

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Abnormal cell metabolism with vigorous nutrition consumption is one of the major physiological characteristics of cancers. As such, the strategy of cancer starvation therapy through blocking the blood supply, depleting glucose/oxygen and other critical nutrients of tumors has been widely studied to be an attractive way for cancer treatment. However, several undesirable properties of these agents, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit their future applications. The recent development of starving-nanotherapeutics combined with other therapeutic methods displayed the promising potential for overcoming the above drawbacks. This review highlights the recent advances of nanotherapeutic-based cancer starvation therapy and discusses the challenges and future prospects of these anticancer strategies.

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“…Another potent strategy is RNAi aimed to knock-down VEGF or VEGFR, which showed good anti-tumor results in many preclinical studies. In this regard, CPPs [ 396 , 397 , 398 , 399 ], polymers like PEI [ 400 , 401 , 402 , 403 ] or chitosan [ 404 ], cationic liposomes [ 405 , 406 ], gold [ 407 ], and graphene oxide NPs [ 408 ], often modified with shielding and targeting units, have been used as delivery systems.…”

Section: Manipulating the Tme Using Therapeutic Nucleic Acidsmentioning

confidence: 99%

Nucleic Acid-Based Approaches for Tumor Therapy

Hager

Fittler

Wagner

et al. 2020

Cells

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Within the last decade, the introduction of checkpoint inhibitors proposed to boost the patients’ anti-tumor immune response has proven the efficacy of immunotherapeutic approaches for tumor therapy. Furthermore, especially in the context of the development of biocompatible, cell type targeting nano-carriers, nucleic acid-based drugs aimed to initiate and to enhance anti-tumor responses have come of age. This review intends to provide a comprehensive overview of the current state of the therapeutic use of nucleic acids for cancer treatment on various levels, comprising (i) mRNA and DNA-based vaccines to be expressed by antigen presenting cells evoking sustained anti-tumor T cell responses, (ii) molecular adjuvants, (iii) strategies to inhibit/reprogram tumor-induced regulatory immune cells e.g., by RNA interference (RNAi), (iv) genetically tailored T cells and natural killer cells to directly recognize tumor antigens, and (v) killing of tumor cells, and reprograming of constituents of the tumor microenvironment by gene transfer and RNAi. Aside from further improvements of individual nucleic acid-based drugs, the major perspective for successful cancer therapy will be combination treatments employing conventional regimens as well as immunotherapeutics like checkpoint inhibitors and nucleic acid-based drugs, each acting on several levels to adequately counter-act tumor immune evasion.

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Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles

Cited by 28 publications

References 22 publications

The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells

The Impact of Nylon-3 Copolymer Composition on the Efficiency of siRNA Delivery to Glioblastoma Cells

Advances in nanomedicine for cancer starvation therapy

Nucleic Acid-Based Approaches for Tumor Therapy

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