Biodegradable nanoparticles as siRNA carriers for in vivo gene silencing and pancreatic cancer therapy

2017 ◽  
Vol 5 (18) ◽  
pp. 3327-3337 ◽  
Author(s):  
Guimiao Lin ◽  
Chih-Kuang Chen ◽  
Feng Yin ◽  
Chengbin Yang ◽  
Jinglin Tian ◽  
...  

Biodegradable charged polyester-based vectors (BCPVs) were utilized for efficiently delivering mutatedK-Ras-targeting siRNA and successfully inhibiting tumor growth in a pancreatic xenograft modelin vivo.

2018 ◽  
Vol 2 (4) ◽  
pp. 371-386 ◽  
Author(s):  
Feng Yin ◽  
Tommy Anderson ◽  
Nishtha Panwar ◽  
Kang Zhang ◽  
Swee Chuan Tjin ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1428
Author(s):  
Dandan Luo ◽  
Xiaochun Xu ◽  
M. Zubair Iqbal ◽  
Qingwei Zhao ◽  
Ruibo Zhao ◽  
...  

Pancreatic carcinoma (PC) is greatly induced by the KRAS gene mutation, but effective targeted delivery for gene therapy has not existed. Small interfering ribonucleic acid (siRNA) serves as an advanced therapeutic modality and holds great promise for cancer treatment. However, the development of a non-toxic and high-efficiency carrier system to accurately deliver siRNA into cells for siRNA-targeted gene silencing is still a prodigious challenge. Herein, polyethylenimine (PEI)-modified hydroxyapatite (HAp) nanoparticles (HAp-PEI) were fabricated. The siRNA of the KRAS gene (siKras) was loaded onto the surface of HAp-PEI via electrostatic interaction between siRNA and PEI to design the functionalized HAp-PEI nanoparticle (HAp-PEI/siKras). The HAp-PEI/siKras was internalized into the human PC cells PANC-1 to achieve the maximum transfection efficiency for active tumor targeting. HAp-PEI/siKras effectively knocked down the expression of the KRAS gene and downregulated the expression of the Kras protein in vitro. Furthermore, the treatment with HAp-PEI/siKras resulted in greater anti-PC cells’ (PANC-1, BXPC-3, and CFPAC-1) efficacy in vitro. Additionally, the HAp-PEI exhibited no obvious in vitro cytotoxicity in normal pancreatic HPDE6-C7 cells. These findings provided a promising alternative for the therapeutic route of siRNA-targeted gene engineering for anti-pancreatic cancer therapy.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 307-307
Author(s):  
Mei-Juan Tu ◽  
Zhijian Duan ◽  
Qianyu Zhang ◽  
Jing-Xin Qiu ◽  
Frank J Gonzalez ◽  
...  

307 Background: MicroRNAs (miR) have proved to be vital regulators in the control of tumor progression. Our recent studies have revealed miR-1291 is downregulated in patient pancreatic cancer (PC) specimens and re-introduction of miR-1291 suppresses tumorigenesis of PC cells. We have developed a novel ncRNA bioengineering technology to produce a miR-1291 prodrug. In this study, we aimed to assess the effectiveness of this miR-1291 prodrug as a monotherapy, as well as in combination with chemotherapy, for treatment of PC. Methods: Sensitivity of PC cells to miR-1291 prodrug alone, gemcitabine plus nab-paclitaxel (Gem-nP) alone, and their combination was evaluated by CellTiter-Glo assay. Mature miR-1291 and ARID3B mRNA levels were determined by quantitative real-time PCR (q-PCR) assay. A luciferase reporter gene assay was used to validate interaction between miR-1291 and ARID3B 3’UTR. Target protein expression was examined by Western blot and immunofluorescence analyses. PANC-1 and PC patient-derived xenograft (PDX) mouse models were established and used to assess anti-tumor effects of miR-1291 monotherapy and combination therapy with Gem-nP. Results: Cytotoxicity assays showed that miR-1291 prodrug enhanced the sensitivity of PANC-1 and AsPC-1 cells to Gem-nP. Luciferase assays confirmed ARID3B as a target for miR-1291 as predicted by computational analysis. qPCR analysis demonstrated that miR-1291 prodrug was readily processed to mature miR-1291 and subsequently upregulated ARID3B mRNA levels. miR-1291 prodrug also elevated the protein levels of ARID3B. Co-administration of miR-1291 prodrug and Gem-nP increased caspase-3/7 and γH2AX levels in PC cells, compared to miR-1291 or Gem-nP treatment alone. In addition, systemic administration of in vivo-jet PEI formulated miR-1291 prodrug suppressed tumor growth in both a PANC-1 xenograft model and three PDX models, and largely enhanced the efficacy of Gem-nP. All treatments were well tolerated in mice in vivo. Conclusions: Our bioengineered miR-1291 prodrug has therapeutic potential as a monotherapy but also can act as a sensitizing agent to chemotherapy. This novel treatment approach should be further explored for PC.


Nanoscale ◽  
2021 ◽  
Author(s):  
Qinglin Sheng ◽  
Ting Li ◽  
Xian Tang ◽  
Wei Zhao ◽  
Rong Guo ◽  
...  

Facing the barriers in each step of the in vivo delivery cascade, the low drug delivery efficiency remains a thorny problem in tumor therapy. Although recently the nanofibril drug delivery...


Nano Letters ◽  
2019 ◽  
Vol 19 (11) ◽  
pp. 7573-7587 ◽  
Author(s):  
Girgis Obaid ◽  
Shazia Bano ◽  
Srivalleesha Mallidi ◽  
Mans Broekgaarden ◽  
Jerrin Kuriakose ◽  
...  

2018 ◽  
Vol 6 (5) ◽  
pp. 1262-1270 ◽  
Author(s):  
Pu Wang ◽  
Jinxiu Wang ◽  
Haowen Tan ◽  
Shanfan Weng ◽  
Liying Cheng ◽  
...  

One of the major challenges in anticancer therapy is the poor penetration of anticancer drugs into tumors, especially in solid tumors, resulting in decreased therapeutic efficacy in vivo.


2013 ◽  
Vol 77 (5) ◽  
pp. AB208-AB209
Author(s):  
Gang Sun ◽  
Marlys Anderson ◽  
Emmanuel C. Gorospe ◽  
Margriet R. Timmer ◽  
Cadman L. Leggett ◽  
...  

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