Evaluate the Effectiveness of RNAi-Based Nanoparticles as Therapy for Pancreatic Cancer
Abstract
Pancreatic cancer is one of the most lethal cancers with limited effective treatment options. RNA interference (RNAi) offers a promising therapeutic approach, but efficient delivery systems are essential. To evaluate the effectiveness of RNAi-based nanoparticles as a therapy for pancreatic cancer, focusing on tumor inhibition and cell viability. A comprehensive study combining in vitro, in vivo, and clinical approaches was conducted. Pancreatic cancer cell lines (PANC-1, BxPC-3, AsPC-1) and mouse models with human pancreatic tumors were treated with RNAi-based nanoparticles. Characterization of nanoparticles included size, charge, and stability assessments using DLS and HPLC. RNAi-based nanoparticles inhibited tumor growth by 70% in mouse models and reduced cell viability by 60% in vitro. Nanoparticles demonstrated high stability and effective internalization into cancer cells, leading to significant gene silencing and apoptotic effects. RNAi-based nanoparticles show significant potential as an effective therapy for pancreatic cancer, demonstrating substantial tumor inhibition and cell viability reduction. Further clinical trials are necessary to confirm these findings and optimize nanoparticle formulations.
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References
Ahmad, S., Shahzad, R., Jamil, S., Tabassum, J., Chaudhary, M. A. M., Atif, R. M., Iqbal, M. M., Monsur, M. B., Lv, Y., Sheng, Z., Ju, L., Wei, X., Hu, P., & Tang, S. (2021). Regulatory aspects, risk assessment, and toxicity associated with RNAi and CRISPR methods. In CRISPR and RNAi Systems (pp. 687–721). Elsevier. https://doi.org/10.1016/B978-0-12-821910-2.00013-8
Bonning, B. C., & Saleh, M.-C. (2021). The Interplay Between Viruses and RNAi Pathways in Insects. Annual Review of Entomology, 66(1), 61–79. https://doi.org/10.1146/annurev-ento-033020-090410
Cao, S., Saw, P. E., Shen, Q., Li, R., Liu, Y., & Xu, X. (2022). Reduction-responsive RNAi nanoplatform to reprogram tumor lipid metabolism and repolarize macrophage for combination pancreatic cancer therapy. Biomaterials, 280, 121264. https://doi.org/10.1016/j.biomaterials.2021.121264
Ehexige, E., Bao, M., Bazarjav, P., Yu, X., Xiao, H., Han, S., & Baigude, H. (2020). Silencing of STAT3 via Peptidomimetic LNP-Mediated Systemic Delivery of RNAi Downregulates PD-L1 and Inhibits Melanoma Growth. Biomolecules, 10(2), 285. https://doi.org/10.3390/biom10020285
Fairman, K., Li, M., Ning, B., & Lumen, A. (2021). Physiologically based pharmacokinetic (PBPK) modeling of RNAi therapeutics: Opportunities and challenges. Biochemical Pharmacology, 189, 114468. https://doi.org/10.1016/j.bcp.2021.114468
Ganbold, T., Bao, Q., Zandan, J., Hasi, A., & Baigude, H. (2020). Modulation of Microglia Polarization through Silencing of NF-?B p65 by Functionalized Curdlan Nanoparticle-Mediated RNAi. ACS Applied Materials & Interfaces, 12(10), 11363–11374. https://doi.org/10.1021/acsami.9b23004
Gong, Y., & Zhang, X. (2021). RNAi-based antiviral immunity of shrimp. Developmental & Comparative Immunology, 115, 103907. https://doi.org/10.1016/j.dci.2020.103907
Han, X., Wang, L., Li, T., Zhang, J., Zhang, D., Li, J., Xia, Y., Liu, Y., & Tan, W. (2020). Beyond Blocking: Engineering RNAi-Mediated Targeted Immune Checkpoint Nanoblocker Enables T-Cell-Independent Cancer Treatment. ACS Nano, 14(12), 17524–17534. https://doi.org/10.1021/acsnano.0c08022
He, C., Yue, H., Xu, L., Liu, Y., Song, Y., Tang, C., & Yin, C. (2020). siRNA release kinetics from polymeric nanoparticles correlate with RNAi efficiency and inflammation therapy via oral delivery. Acta Biomaterialia, 103, 213–222. https://doi.org/10.1016/j.actbio.2019.12.005
Hung, Y.-H., & Slotkin, R. K. (2021). The initiation of RNA interference (RNAi) in plants. Current Opinion in Plant Biology, 61, 102014. https://doi.org/10.1016/j.pbi.2021.102014
Jiang, T., Qiao, Y., Ruan, W., Zhang, D., Yang, Q., Wang, G., Chen, Q., Zhu, F., Yin, J., Zou, Y., Qian, R., Zheng, M., & Shi, B. (2021). Cation?Free siRNA Micelles as Effective Drug Delivery Platform and Potent RNAi Nanomedicines for Glioblastoma Therapy. Advanced Materials, 33(45), 2104779. https://doi.org/10.1002/adma.202104779
Jin, Y., Zhao, J.-H., & Guo, H.-S. (2021). Recent advances in understanding plant antiviral RNAi and viral suppressors of RNAi. Current Opinion in Virology, 46, 65–72. https://doi.org/10.1016/j.coviro.2020.12.001
Kara, G., Calin, G. A., & Ozpolat, B. (2022). RNAi-based therapeutics and tumor targeted delivery in cancer. Advanced Drug Delivery Reviews, 182, 114113. https://doi.org/10.1016/j.addr.2022.114113
Kelleher, A. D., Cortez-Jugo, C., Cavalieri, F., Qu, Y., Glanville, A. R., Caruso, F., Symonds, G., & Ahlenstiel, C. L. (2020). RNAi therapeutics: An antiviral strategy for human infections. Current Opinion in Pharmacology, 54, 121–129. https://doi.org/10.1016/j.coph.2020.09.011
Kim, D. S., & Zhang, J. (2023). Strategies to improve the efficiency of RNAi-mediated crop protection for pest control. Entomologia Generalis, 43(1), 5–19. https://doi.org/10.1127/entomologia/2022/1638
Kimura, Y., Shu, Z., Ito, M., Abe, N., Nakamoto, K., Tomoike, F., Shuto, S., Ito, Y., & Abe, H. (2020). Intracellular build-up RNAi with single-strand circular RNAs as siRNA precursors. Chemical Communications, 56(3), 466–469. https://doi.org/10.1039/C9CC04872C
Kolge, H., Kadam, K., Galande, S., Lanjekar, V., & Ghormade, V. (2021). New Frontiers in Pest Control: Chitosan Nanoparticles-Shielded dsRNA as an Effective Topical RNAi Spray for Gram Podborer Biocontrol. ACS Applied Bio Materials, 4(6), 5145–5157. https://doi.org/10.1021/acsabm.1c00349
Kyre, B. R., Bentz, B. J., & Rieske, L. K. (2020). Susceptibility of mountain pine beetle (Dendroctonus ponderosae Hopkins) to gene silencing through RNAi provides potential as a novel management tool. Forest Ecology and Management, 473, 118322. https://doi.org/10.1016/j.foreco.2020.118322
Laird, N. Z., Acri, T. M., Tingle, K., & Salem, A. K. (2021). Gene- and RNAi-activated scaffolds for bone tissue engineering: Current progress and future directions. Advanced Drug Delivery Reviews, 174, 613–627. https://doi.org/10.1016/j.addr.2021.05.009
Laisney, J., Gurusamy, D., Baddar, Z. E., Palli, S. R., & Unrine, J. M. (2020). RNAi in Spodoptera frugiperda Sf9 Cells via Nanomaterial Mediated Delivery of dsRNA: A Comparison of Poly- L -arginine Polyplexes and Poly- L -arginine-Functionalized Au Nanoparticles. ACS Applied Materials & Interfaces, 12(23), 25645–25657. https://doi.org/10.1021/acsami.0c06234
Lee, S., Kim, S., Koo, D.-J., Yu, J., Cho, H., Lee, H., Song, J. M., Kim, S.-Y., Min, D.-H., & Jeon, N. L. (2021). 3D Microfluidic Platform and Tumor Vascular Mapping for Evaluating Anti-Angiogenic RNAi-Based Nanomedicine. ACS Nano, 15(1), 338–350. https://doi.org/10.1021/acsnano.0c05110
Li, K., Zhang, Y., Hussain, A., Weng, Y., & Huang, Y. (2021). Progress of Photodynamic and RNAi Combination Therapy in Cancer Treatment. ACS Biomaterials Science & Engineering, 7(9), 4420–4429. https://doi.org/10.1021/acsbiomaterials.1c00765
Li, Q., Lv, X., Tang, C., & Yin, C. (2022). Co-delivery of doxorubicin and CRISPR/Cas9 or RNAi-expressing plasmid by chitosan-based nanoparticle for cancer therapy. Carbohydrate Polymers, 287, 119315. https://doi.org/10.1016/j.carbpol.2022.119315
Liu, X., Xie, X., Zheng, C., Wei, L., Li, X., Jin, Y., Zhang, G., Jiang, C.-J., & Liang, Z. (2022). RNAi-mediated suppression of the abscisic acid catabolism gene OsABA8ox1 increases abscisic acid content and tolerance to saline–alkaline stress in rice (Oryza sativa L.). The Crop Journal, 10(2), 354–367. https://doi.org/10.1016/j.cj.2021.06.011
Liu, Z., Zhao, L., Huang, L., Qin, Y., Zhang, J., Zhang, J., & Yan, Q. (2020). Integration of RNA-seq and RNAi provides a novel insight into the immune responses of Epinephelus coioides to the impB gene of Pseudomonas plecoglossicida. Fish & Shellfish Immunology, 105, 135–143. https://doi.org/10.1016/j.fsi.2020.06.023
Mujtaba, M., Wang, D., Carvalho, L. B., Oliveira, J. L., Espirito Santo Pereira, A. D., Sharif, R., Jogaiah, S., Paidi, M. K., Wang, L., Ali, Q., & Fraceto, L. F. (2021). Nanocarrier-Mediated Delivery of miRNA, RNAi, and CRISPR-Cas for Plant Protection: Current Trends and Future Directions. ACS Agricultural Science & Technology, 1(5), 417–435. https://doi.org/10.1021/acsagscitech.1c00146
Obici, L., Berk, J. L., González-Duarte, A., Coelho, T., Gillmore, J., Schmidt, H. H.-J., Schilling, M., Yamashita, T., Labeyrie, C., Brannagan, T. H., Ajroud-Driss, S., Gorevic, P., Kristen, A. V., Franklin, J., Chen, J., Sweetser, M. T., Wang, J. J., & Adams, D. (2020). Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis. Amyloid, 27(3), 153–162. https://doi.org/10.1080/13506129.2020.1730790
Riga, M., Denecke, S., Livadaras, I., Geibel, S., Nauen, R., & Vontas, J. (2020). Development of efficient RNAi in Nezara viridula for use in insecticide target discovery. Archives of Insect Biochemistry and Physiology, 103(3), e21650. https://doi.org/10.1002/arch.21650
Saify Nabiabad, H., Amini, M., & Demirdas, S. (2022). Specific delivering of RNAi using Spike’s aptamer?functionalized lipid nanoparticles for targeting SARS?CoV?2: A strong anti?Covid drug in a clinical case study. Chemical Biology & Drug Design, 99(2), 233–246. https://doi.org/10.1111/cbdd.13978
Schwartz-Orbach, L., Zhang, C., Sidoli, S., Amin, R., Kaur, D., Zhebrun, A., Ni, J., & Gu, S. G. (2020). Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3. eLife, 9, e54309. https://doi.org/10.7554/eLife.54309
Še?i?, E., & Kogel, K.-H. (2021). Requirements for fungal uptake of dsRNA and gene silencing in RNAi-based crop protection strategies. Current Opinion in Biotechnology, 70, 136–142. https://doi.org/10.1016/j.copbio.2021.04.001
Uddin, N., Binzel, D. W., Shu, D., Fu, T.-M., & Guo, P. (2023). Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome. Acta Pharmaceutica Sinica B, 13(4), 1383–1399. https://doi.org/10.1016/j.apsb.2022.11.019
Wang, J., Chen, G., Liu, N., Han, X., Zhao, F., Zhang, L., & Chen, P. (2022). Strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes. Advances in Colloid and Interface Science, 302, 102638. https://doi.org/10.1016/j.cis.2022.102638
Wiltshire, R. M., & Duman-Scheel, M. (2020). Advances in oral RNAi for disease vector mosquito research and control. Current Opinion in Insect Science, 40, 18–23. https://doi.org/10.1016/j.cois.2020.05.002
Xin, G., Wang, F., Zhao, L., Qin, Y., Huang, L., & Yan, Q. (2020). Integration of RNA-seq and RNAi provides a novel insight into the effect of pvdE gene to the pathogenic of Pseudomonas plecoglossicida and on the immune responses of orange-spotted grouper (Epinephelus coioides). Aquaculture, 529, 735695. https://doi.org/10.1016/j.aquaculture.2020.735695
Xu, L., Faruqu, F. N., Lim, Y. M., Lim, K. Y., Liam-Or, R., Walters, A. A., Lavender, P., Fear, D., Wells, C. M., Tzu-Wen Wang, J., & Al-Jamal, K. T. (2021). Exosome-mediated RNAi of PAK4 prolongs survival of pancreatic cancer mouse model after loco-regional treatment. Biomaterials, 264, 120369. https://doi.org/10.1016/j.biomaterials.2020.120369
Yan, S., Ren, B., Zeng, B., & Shen, J. (2020). Improving RNAi Efficiency for Pest Control in Crop Species. BioTechniques, 68(5), 283–290. https://doi.org/10.2144/btn-2019-0171
Yue, D., Cai, X., Fan, M., Zhu, J., Tian, J., Wu, L., Jiang, Q., & Gu, Z. (2021). An Alternating Irradiation Strategy?Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis. Advanced Healthcare Materials, 10(8), 2001850. https://doi.org/10.1002/adhm.202001850
Zhang, D., Sun, Y., Wang, S., Zou, Y., Zheng, M., & Shi, B. (2022). Brain?Targeting Metastatic Tumor Cell Membrane Cloaked Biomimetic Nanomedicines Mediate Potent Chemodynamic and RNAi Combinational Therapy of Glioblastoma. Advanced Functional Materials, 32(51), 2209239. https://doi.org/10.1002/adfm.202209239
Zhang, K., Wei, J., Huff Hartz, K. E., Lydy, M. J., Moon, T. S., Sander, M., & Parker, K. M. (2020). Analysis of RNA Interference (RNAi) Biopesticides: Double-Stranded RNA (dsRNA) Extraction from Agricultural Soils and Quantification by RT-qPCR. Environmental Science & Technology, 54(8), 4893–4902. https://doi.org/10.1021/acs.est.9b07781
Zhang, W., Han, B., Lai, X., Xiao, C., Xu, S., Meng, X., Li, Z., Meng, J., Wen, T., Yang, X., Liu, J., & Xu, H. (2020). Stiffness of cationized gelatin nanoparticles is a key factor determining RNAi efficiency in myeloid leukemia cells. Chemical Communications, 56(8), 1255–1258. https://doi.org/10.1039/C9CC09068A
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