Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment

Luo, Li; Yang, Yuping; Du, Ting; Kang, Tianyi; Xiong, Meimei; Cheng, Hao; Liu, Yu; Wu, Yujiao; Yang, Li; Chen, Yu‐Wen; Zhang, Qianqian; Li, Xuan; Wei, Xiawei; Mi, Peng; She, Zhigang; Gao, Guangping; Wei, Yuquan; Gou, Maling

doi:10.1002/adfm.201800173

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…iDPP was prepared by the previously described method. 30 To prepare the iDPP/DNA nanocomplex, we mixed the iDPP nanoparticle with plasmid DNA at a mass ratio of 25:1 by gentle pipetting and then incubated at room temperature for 30 min. Particle size and zeta potential of the nanocomplex were determined by a dynamic light scattering detector (Malvern Nano-ZS90, UK) with a 2 min of equilibration time at 25 °C.…”

Section: Methodsmentioning

confidence: 99%

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Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor

Min¹,

Xiong²,

Li³

et al. 2021

IJN

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Introduction Peptides can be rationally designed as non-covalent inhibitors for molecularly targeted therapy. However, it remains challenging to efficiently deliver the peptides into the targeted cells, which often severely affects their therapeutic efficiency. Methods Herein, we created a novel non-covalent peptide inhibitor against nuclear export factor CRM1 by a structure-guided drug design method and targetedly delivered the peptide into cancer cells by a nanoparticle-mediated gene expression system for use as a cancer therapy. Results The nuclear export signal (NES)-optimized CRM1 peptide inhibitor colocalized with CRM1 to the nuclear envelope and inhibited nuclear export in cancer cell lines in vitro. The crystal structures of the inhibitors complexed with CRM1 were solved. In contrast to the covalent inhibitors, the peptides were similarly effective against cells harboring the CRM1 C528S mutation. Moreover, a plasmid encoding the peptides was delivered by a iRGD-modified nanoparticle to efficiently target and transfect the cancer cells in vivo after intravenous administration. The peptides could be selectively expressed in the tumor, resulting in the efficient inhibition of subcutaneous melanoma xenografts without obvious systemic toxicity. Discussion This work provides an effective strategy to design peptide-based molecularly targeted therapeutics, which could lead to the development of future targeted therapy.

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Section: Methodsmentioning

confidence: 99%

“… 29 In our previous work, we developed an iDPP gene delivery system that could selectively deliver the DNAs into the tumor cells after intravenous administration. 30 This platform could provide a tool for intracellular expression of a peptide discovered through structure-guided drug design.…”

Section: Introductionmentioning

confidence: 99%

Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor

Min¹,

Xiong²,

Li³

et al. 2021

IJN

Self Cite

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“…To overcome this obstacle, non-cationic nanocarriers for safe and effective gene delivery should be explored. Our previous studies have demonstrated that the biodegradable nanoparticles (iDPP), which were prepared by self-assembly of a tumor-targeted peptide (C18-PEG-iRGD), monomethoxy poly(ethlene glycol)-poly(D,L-lactide) (mPEG-PLA), and N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTAP), could safely and efficiently deliver genes into melanoma cells 30…”

Section: Introductionmentioning

confidence: 99%

<p>Targeted nanoparticle-mediated LHPP for melanoma treatment</p>

Zhang¹,

Xiong²,

Liu³

et al. 2019

IJN

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Background: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a novel tumor suppressor. However, whether LHPP is effective to melanoma has not been investigated. Gene therapy provides a new strategy for the treatment of melanoma. Currently, it suffers from the lack of safe and effective gene delivery systems. Methods: A CRGDKGPDC peptide (iRGD) modified hybrid monomethoxy poly(ethylene glycol)-poly(D,L-lactide) nanoparticle (iDPP) was prepared and complexed with a LHPP plasmid, forming an iDPP/ LHPP nanocomplex. The iDPP/ LHPP nanocomplex was characterized by particle size distribution, zeta potential, morphology, cytotoxicity, and transfection efficiency. The antitumor efficacy of the nanocomplex against melanoma was studied both in vitro and in vivo. Further, the potential epigenetic changes in melanoma induced by iDPP/ LHPP nanocomplex were evaluated. Results: The iDPP/ LHPP nanocomplex showed high transfection efficiency and low toxicity. Moreover, the nanocomplex displayed a neutral charge that can meet the requirement of intravenous injection for targeted gene therapy. In vitro and in vivo experiments indicated that the iDPP/ LHPP nanocomplex significantly inhibited the melanoma growth without causing notable adverse effects. We also found that LHPP played an important role in epigenetics. It regulated the expression of genes related to the proliferation and apoptosis chiefly at the level of transcription. Conclusion: This work demonstrates that the iDPP nanoparticle-delivered LHPP gene has a potential application in melanoma therapy through regulation of the genes associated with epigenetics.

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“…The resulting virus‐mimetic nanocomplex can effectively express VSVMP into ovarian cancer cells and ultimately inhibit intraperitoneal metastatic ovarian cancer. In another study, Luo et al (2018) loaded plasmids encoding VSVMP into tumor‐targeting peptide (C18‐PEG‐iRGD)‐modified neutral nanovectors. The resulting virus‐mimetic nanoparticles could be specifically taken up by melanoma cells and express VSVMP intracellularly, exhibiting effective targeting and inhibition of melanoma.…”

Section: Virus‐mimetic Systems For Tumor Therapymentioning

confidence: 99%

Virus‐mimetic systems for cancer diagnosis and therapy

Gao

Ding

Long

et al. 2020

WIREs Nanomed Nanobiotechnol

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Over past decades, various strategies have been developed to enhance the delivery efficiency of therapeutics and imaging agents to tumor tissues. However, the therapeutic outcome of tumors to date have not been significantly improved, which can be partly attributed to the weak targeting ability, fast elimination, and low stability of conventional delivery systems. Viruses are the most efficient agents for gene transfer, serving as a valuable source of inspiration for designing nanoparticle‐based delivery systems. Based on the properties of viruses, including well‐defined geometry, precise composition, easy modification, stable construction, and specific infection, researchers attempt to design biocompatible delivery vectors by mimicking virus assembly and using the vector system to selectively concentrate drugs or imaging probes in tumors with mitigated toxicity and improved efficacy. In this review, we introduce common viruses features and provide an overview of various virus‐mimetic strategies for cancer therapy and diagnosis. The challenges faced by virus‐mimetic systems are also discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment

Cited by 16 publications

References 42 publications

Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor

Cancer Therapy with Nanoparticle-Medicated Intracellular Expression of Peptide CRM1-Inhibitor

<p>Targeted nanoparticle-mediated LHPP for melanoma treatment</p>

Virus‐mimetic systems for cancer diagnosis and therapy

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