Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer

Zhou, Yue; Zhang, Qing; Wang, Minjia; Huang, Chengzhi; Yao, Xueqing

doi:10.3389/fonc.2022.827891

Cited by 6 publications

(9 citation statements)

References 35 publications

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“…To further analyze the potential association between SH3TC2 and CRC, IHC analysis was performed as previously described [ 48 , 49 , 50 ]. The list of antibodies and dilution fold can be found in Supplementary Materials Table S2 .…”

Section: Methodsmentioning

confidence: 99%

“…We performed qRT-PCR analysis as previously described [ 48 , 49 , 50 ]. Briefly, total RNA was extracted by Total RNA Isolation Reagent (BS258A, Biosharp, Shanghai, China) and reverse transcribed into complementary DNA (cDNA) by the First-strand cDNA Synthesis Kit (K1072, Apexbio, Huston, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was utilized to examine the protein expression level of SH3TC2 and its related proteins in CRC cell lines. The experiments were performed as previously described [ 49 , 50 ]. The list of antibodies and dilution fold can be found in Supplementary Materials Table S2 .…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Huang

Zhou

et al. 2022

Cancers

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SH3 domain and tetrapeptide repeat 2 (SH3TC2) is a protein-encoding gene and has previously been described as a critical signaling hub for neurological disorders. Although increasing evidence supports a vital role of SH3TC2 in the tumorigenesis of various kinds of cancer, no systematic analysis of SH3TC2 is available. The function and mechanism of SH3TC2 in other cancers remain unknown. Thus, this study aimed to analyze SH3TC2 in various kinds of cancer to find its tumorigenic role in one or more specific cancers. In the current study, we analyzed the expression level and prognostic value of SH3TC2 in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of SH3TC2 in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of SH3TC2 in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, SH3TC2 showed a significant effect on the clinical stage and prognostic value in CRC, LAML, and SKCM. Moreover, we found in the TCGA database and seven GEO datasets that SH3TC2 was significantly highly expressed in tumor tissue. Through enrichment analysis of SH3TC2 and its co-expressed genes, we found that SH3TC2 may play a role in the MAPK signaling pathway. Correlation analysis indicated that SH3TC2 was significantly associated with multiple key factors in the MAPK signaling pathway. Additionally, higher expression of SH3TC2 was found in tumor tissue in our cohort including 40 CRC patients. Overexpression of SH3TC2 may imply poor prognosis. Knockdown of SH3TC2 significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of SH3TC2 inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of SH3TC2 and further explored the mechanism of SH3TC2 in CRC. Our research revealed that higher expression of SH3TC2 may promote CRC progression and invasion via the MAPK signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Huang

Zhou

et al. 2022

Cancers

Self Cite

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“…ATP7A is one of the key regulators of the intracellular level of platinum-based drug such as Oxaliplatin (OXA) [ 105 ], commonly used to treat colon cancer patients. Based on this knowledge, Zhou et al [ 99 ] delivered to the colon cancer cells HCT116 and LOVO a siRNA (siATP7A) by means of a lipid based delivery system. Besides reaching good down-regulation in the expression of the target gene, the authors could also show that cells treated by siATP7A displayed increased sensibility to OXA.…”

Section: Sirnas For the Gi Cancersmentioning

confidence: 99%

Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors

et al. 2022

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Despite the progress made in the diagnoses and therapy of gastrointestinal cancers, these diseases are still plagued by a high mortality. Thus, novel therapeutic approaches are urgently required. In this regard, small interfering RNA (siRNA), double-stranded RNA molecules able to specifically target the mRNA of pathological genes, have the potential to be of therapeutic value. To be effective in the human body, siRNAs need to be protected against degradation. Additionally, they need to target the tumor, leaving the normal tissue untouched in an effort to preserve organ function. To accomplish these tasks, siRNAs have been formulated with smart delivery systems such has polymers and lipids. While siRNA protection is not particularly difficult to achieve, their targeting of tumor cells remains problematic. Here, after introducing the general features of gastrointestinal cancers, we describe siRNA characteristics together with representative delivery systems developed for gastrointestinal cancers. Afterward, we present a selection of research papers employing siRNAs against upper- and lower- gastrointestinal cancers. For the liver, we also consider papers using siRNAs to combat liver cirrhosis, a relevant risk factor for liver cancer development. Finally, we present a brief description of clinical trials employing siRNAs for gastrointestinal cancers.

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“…Strategy of co-delivering chemotherapeutics and siRNA targeting chemoresistance-related machinery has been proposed and studied widely in treating malignant cancers such as colorectal cancer. 22 , 23 Polymer nanoparticles 24 and inorganic nanoparticles 25 have been used as nanoplatform for co-delivering siRNA and drugs. They discovered that co-delivery strategy not only enhances drug delivery through penetration into tumor tissues but also antagonizes chemoresistance by modulating chemoresistance-associated genes.…”

Section: Introductionmentioning

confidence: 99%

Carbon Dots-Based Nanozyme for Drug-Resistant Lung Cancer Therapy by Encapsulated Doxorubicin/siRNA Cocktail

Yu¹,

Tang²,

Cai³

et al. 2023

IJN

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Background Nanomaterials exhibited intrinsic enzyme-like properties due to the unique properties compared with natural enzyme. Carbon dots (CDs) are an important kind of quantum-sized nanomaterials, which have enormous application potential in bio-imaging, drug carrier, and nanosystems. Carbon dots possess intrinsic enzyme-like properties, such as glutathione (GSH) oxidase or peroxidase activities. Methods A co-delivery nanosystem that could carry siRNA and doxorubucin (DOX) simultaneously has been studied in this work. The co-delivery based on carbon dots was surface-modified with poly-ethylenimine (PEI) and loaded the siMRP1 with chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI was raw materials and passivator during the reaction process that makes CDs exhibit excellent optical property. Results The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumors and releasing them synchronously in cells in an acid-triggered manner. The particles exhibited GSH oxidase-like catalytic property, oxidizing GSH to oxidized glutathione with concomitant increase of reactive oxygen species (ROS). We found that silencing of MRP1 by co-delivery system antagonized chemoresistance by increasing DOX accumulation and significantly enhancing the inhibitory effect of cell viability induced by CD-PEI-DOX. The co-delivery system dramatically inhibited tumor growth in xenograft model, and CDs counteracted MRP1 function by siRNA-mediated knockdown of MRP1. Conclusion Taken together, we uncover the potential role of CDs with a combination of siRNA and chemotherapeutics in overcoming chemoresistance of lung cancer by suppressing MRP1 and oxidation of GSH. Our findings imply its potential of antagonizing chemoresistance to enhance therapeutic efficiency of doxorubicin in clinical practices of lung cancer treatment.

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Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer

Cited by 6 publications

References 35 publications

Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway

Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors

Carbon Dots-Based Nanozyme for Drug-Resistant Lung Cancer Therapy by Encapsulated Doxorubicin/siRNA Cocktail

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