Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer

Liu, Huan; Gao, Xiang; Zheng, Songping; Wang, Bilan; Li, Yanyan; Zhao, Chanjuan; Muftuoglu, Yagmur; Chen, Song; Li, Ying; Yao, Huaiying; Sun, Hui; Mao, Qinghe; You, Chao; Guo, Gang; Wei, Yuquan

doi:10.1016/j.nano.2017.04.006

Cited by 52 publications

(31 citation statements)

References 43 publications

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“…Gene therapy involves the delivery of DNA, RNA, small interfering RNAs, or antisense oligonucleotides 7 - 9 . Thus far, most of the clinical trials in gene therapy for cancer treatment report remarkable efficacies both in vitro and in vivo 1 .…”

Section: Introductionmentioning

confidence: 99%

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system

Liu¹,

Li²,

Sun³

et al. 2018

Theranostics

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Rationale: Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world. Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year. Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC.Methods: In this study, we developed a novel gene delivery system with a self-assembly method using DOTAP and MPEG-PLA (DMA) to carry pIL15, denoted as DMA-pIL15 which was used to treat tumor-bearing mice.Results: Supernatant from lymphocytes treated with supernatant derived from CT26 cells transfected with DMA-pIL15 inhibited the growth of CT26 cells and induced cell apoptosis in vitro. Treatment of tumor-bearing mice with DMA-pIL15 complex significantly inhibited tumor growth in both subcutaneous and peritoneal models in vivo by inhibiting angiogenesis, promoting apoptosis, and reducing proliferation through activation of the host immune system.Conclusion: The IL-15 plasmid and DMA complex showed promise for treating CRC clinically as an experimental new drug.

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Section: Introductionmentioning

confidence: 99%

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system

Liu¹,

Li²,

Sun³

et al. 2018

Theranostics

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“…The better performing vectors 7 , 10 , and 11 were selected for further assessing their aptitude to complex plasmid pCMV‐IL12, which encodes the potent antitumoral cytokine interleukin‐12 (IL‐12), and deliver it into HepG2 cells. CDplexes formulated with the secondary‐face‐linked vectors 10 and 11 achieved slightly higher efficiencies than the primary‐face‐linked counterpart 7 in this assay.…”

Section: Resultsmentioning

confidence: 99%

“…It is interesting to speculate that the lessordered internal structure of the corresponding CD/pDNA nanocomplexes, as evidenced by SAXS, translate into al ower compactness, beneficially impacting cargo release in the cell. [86,87] The better performing vectors 7, 10,a nd 11 were selected for furthera ssessing their aptitude to complex plasmidp CMV-IL12, which encodes the potent antitumoralc ytokinei nterleukin-12 (IL-12), [88,89] and deliver it into HepG2c ells. CDplexes formulatedw ith the secondary-face-linked vectors 10 and 11 achieved slightly higher efficiencies than the primary-face-linked counterpart 7 in this assay.M ost importantly,t he three molecular vectors performed outstandingly better than bPEI, leading to 55-to 115-foldh igher IL-12 expressions (Figure 7).…”

Section: Cell Transfectioncapabilities In Vitromentioning

confidence: 99%

Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular Vector Design for Effective Gene Delivery

Gallego‐Yerga

Benito

Blanco‐Fernández

et al. 2018

Chemistry A European J

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Engineering self-assembled superstructures through complexation of plasmid DNA (pDNA) and single-isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self-assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)-based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod-type, or worm-like nanoparticles, which makes it possible to gain understanding of their shape-dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross-linking interactions on going from primary-face- to secondary-face-linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue-selective DNA delivery to the spleen in vivo.

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“…One way to go forward would be by using multiple gene targets. For example, combining VEGF targeting has shown to be synergistic with HIF‐1ɑ targeting, and another interesting approach would be to use plasmid encoding IL‐12 or IL‐12‐based cytokine combination therapies …”

Section: Discussionmentioning

confidence: 99%

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

et al. 2018

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Gene therapy is a prospective strategy for treating cancer. However, finding efficient and tumor‐specific gene delivery vectors remains an issue. Tumor responsive cell‐penetrating peptide (CPP) PepFect144 (PF144) has previously been shown to deliver reporter gene encoding plasmid DNA specifically into tumors upon systemic administration, but its capability to reduce tumor growth has not yet been evaluated. Here, we study the potential of PF144‐based anti‐angiogenic gene delivery to inhibit tumor growth by silencing vascular endothelial growth factor (VEGF) expression in tumors. This approach led to the inhibition of tumor growth in both the HT1080 fibrosarcoma model and orthotopic 4T1 breast tumor model. We additionally saw that the addition of αvβ3 integrin targeting did not further improve the tumor sensitive CPPs. Our results suggest that activatable cell‐penetrating peptide PF144 is a promising nonviral plasmid DNA delivery vector for cancer treatment.

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Modified nanoparticle mediated IL-12 immunogene therapy for colon cancer

Cited by 52 publications

References 43 publications

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system

Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular Vector Design for Effective Gene Delivery

Tumor gene therapy by systemic delivery of plasmid DNA with cell-penetrating peptides

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