Stromal Modulation and Treatment of Metastatic Pancreatic Cancer with Local Intraperitoneal Triple miRNA/siRNA Nanotherapy

Xie, Ying; H, Yu; Wang, Yazhe; Sleightholm, Richard; Prajapati, Dipakkumar R.; Bader, J.F.; Yu, Ao; Tang, Weimin; Jaramillo, Lee; Li, Jing; Singh, Rakesh K.; Oupický, David

doi:10.1021/acsnano.9b03978

Cited by 102 publications

(108 citation statements)

References 73 publications

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“…Validating effective RNA treatment strategies in a number of cancer treatment studies [18][19][20][21][22][23][24] can also be used as an adjuvant treatment for DCM. In the future, we can construct a nanotargeted therapeutic system by designing miRNA overexpression vector gene drugs together with chemical drugs through rational encapsulation of nanomaterials such as cationic polymers and liposomes and connecting cardiac-targeting ligands in the outer layer [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Identification of lncRNA-miRNA-mRNA Network in Dilated Cardiomyopathy and Drug Prediction

Liu

Cai

Tang

et al. 2021

Journal of Nanomaterials

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Background. Dilated cardiomyopathy (DCM) is a cardiovascular disease of unknown etiology with progressive aggravation. More and more studies have shown that long noncoding RNAs (lncRNAs) play an essential role in dilated cardiomyopathy formation and development. The mechanism of action of competitive endogenous RNA (ceRNA) networks formed based on the principle that lncRNAs affect mRNAs’ expression level by competitively binding microRNAs (miRNAs) in dilated cardiomyopathy has rarely been reported. Objective. This study is aimed at constructing a lncRNA-miRNA-mRNA ceRNA network by bioinformatics analysis methods, discovering, and validating potential biomarkers of DCM in the ceRNA network and determining possible therapeutic targets from them for drug prediction. Methods. A lncRNA dataset and a mRNA microarray dataset were downloaded from the Gene Expression Omnibus Database (GEO). Gene expression was compared between blood samples from patients with dilated cardiomyopathy and blood samples from normal subjects to identify differential expression of lncRNAs and mRNAs. The lncRNA-miRNA-mRNA network was constructed using bioinformatics tools, and functional and pathway enrichment analysis and protein-protein interactions were performed. The mRNAs in the network and the proteins they encode are then used as targets for predicting drugs. Besides, the expression of lncRNAs in the ceRNA network was validated by real-time quantitative PCR (qRT-PCR) experiments in vitro. Results. The differentially expressed lncRNA-miRNA-mRNA ceRNA network in dilated cardiomyopathy was successfully established. Two differentially overexpressed key lncRNAs were found from the network: AC093817 and AC091062, and qRT-PCR experiments further validated the overexpression of AC093817 and AC091062. The mRNAs in the network and the proteins encoded by the mRNAs were used for drug prediction to get related drugs. Conclusion. This study supports a possible mechanism and drug development of dilated cardiomyopathy, AC093817 and AC091062 being potential biomarkers of dilated cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Identification of lncRNA-miRNA-mRNA Network in Dilated Cardiomyopathy and Drug Prediction

Liu

Cai

Tang

et al. 2021

Journal of Nanomaterials

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“…At this time point, the bio‐distribution analysis indicated that the intra‐tumor accumulation efficiency of COi6‐4Cl NPs was ≈8.0% ID g −1 (Figure S21, Supporting Information), which was a relatively good result among the similar passivate delivery system through the EPR effect. [ 18 ] Notably, the fluorescence signals at tumor sites after 48 h post injection were still high, which indicated that COi6‐4Cl could serve as a long‐term NIR‐II fluorescence imaging agent.…”

Section: Methodsmentioning

confidence: 99%

An NIR‐II‐Emissive Photosensitizer for Hypoxia‐Tolerant Photodynamic Theranostics

et al. 2020

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As a common feature in a majority of malignant tumors, hypoxia has become the Achilles’ heel of photodynamic therapy (PDT). The development of type‐I photosensitizers that show hypoxia‐tolerant PDT efficiency provides a straightforward way to address this issue. However, type‐I PDT materials have rarely been discovered. Herein, a π‐conjugated molecule with A–D–A configuration, COi6‐4Cl, is reported. The H2O‐dispersible nanoparticle of COi6‐4Cl can be activated by an 880 nm laser, and displays hypoxia‐tolerant type I/II combined PDT capability, and more notably, a high NIR‐II fluorescence with a quantum yield over 5%. Moreover, COi6‐4Cl shows a negligible photothermal conversion effect. The non‐radiative decay of COi6‐4Cl is suppressed in the dispersed and aggregated state due to the restricted molecular vibrations and distinct intermolecular steric hindrance induced by its four bulky side chains. These features make COi6‐4Cl a distinguished single‐NIR‐wavelength‐activated phototheranostic material, which performs well in NIR‐II fluorescence‐guided PDT treatment and shows an enhanced in vivo anti‐tumor efficiency over the clinically approved Chlorin e6, by the equal stresses on hypoxia‐tolerant anti‐tumor therapy and deep‐penetration imaging. Therefore, the great potential of COi6‐4Cl in precise PDT cancer therapy against hypoxia challenges is demonstrated.

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“…Tumor cells have barriers to protect them from the body's immune system, such as an impenetrable stroma and immunosuppressive cells in the tumor environment [60]. Tumor cells block antigen overexpression and increase regulatory-T cells and hence escape the immune system of the body.…”

Section: Application In Immunotherapymentioning

confidence: 99%

Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments

Bhattacharya¹,

Gore²

2021

Advances in Precision Medicine Oncology

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Cancer is caused by an uncontrolled cell division, forming a tumor capable of metastasis. Cancer is the second leading cause of death worldwide. Conventional treatments kill healthy cells, causing side effects. Recently, nanomaterials are explored due to properties such as as- nano-size, high loading, and ligands’ attachment for a selective delivery. Apart from normal body cells, cancer cells express many receptors in excess, which serve as ‘targets’ for attacking the cells. Various ligands like proteins, peptides, polysaccharides can be attached to nanoparticles to allow proper and specific reach to the tumor. Such nanoparticles go to their desired site and stick onto the receptors, taken inside the cells by various methods. Antibodies are natural proteins that bind to foreign substances and remove them. IgG being the most explored antibody, suffers from many disadvantages such as non-specificity for required antigen, limited binding sites, low tumor penetration. Hence many researchers experimented by removing and adjusting the binding sites, using only the binding sites, enhancing the valency of naturally available IgG. It gave many benefits such as enhanced penetration, reduced immunogenicity, better delivery of drugs with fewer side effects. Continuing advancements in the field of protein engineering will help scientists to come up with better solutions. The properties allow easy surface interaction and entry, achieve better biodistribution, and reduce the amount of drug required. Targeting is based on Paul Ehrlich’s ‘magic bullet, ‘where the therapeutic moiety has two parts-one to identify the target and the second to eliminate it. This concept is revised to incorporate a third component, a carrier. Many nanocarriers can be used to target cancer cells containing ligands to identify malignant cells. Approaches to targeting are passive, active and physical targeting. Many such nanoparticles are in clinical trials and can be a better solution to cancer therapy.

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Stromal Modulation and Treatment of Metastatic Pancreatic Cancer with Local Intraperitoneal Triple miRNA/siRNA Nanotherapy

Cited by 102 publications

References 73 publications

Bioinformatics-Based Identification of lncRNA-miRNA-mRNA Network in Dilated Cardiomyopathy and Drug Prediction

Bioinformatics-Based Identification of lncRNA-miRNA-mRNA Network in Dilated Cardiomyopathy and Drug Prediction

An NIR‐II‐Emissive Photosensitizer for Hypoxia‐Tolerant Photodynamic Theranostics

Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments

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