Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Culture and Seeding
2.3. Synthesis of SSNs and Na-Glc-SSNs
2.4. Particle Size, Zeta Potential Measurements and Observation of SSNs and Na-Glc-SSNs
2.5. Characterization of Particles by a Field Emission Scanning Electron Microscope (FE-SEM) and an Energy Dispersive X-ray (EDX) Analyzer
2.6. Characterization of NPs by Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Diffraction (XRD)
2.7. Acid Dissolution Study of SSNs and Na-Glc-SSNs
2.8. Assessment of siRNA Binding Affinity to Particles
2.9. Cellular Uptake of siRNA-Loaded NPs
2.10. Cell Viability Assay with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)
2.11. In-Solution Digestion of SSN and Na-Glc-SSN Protein Corona for Mass Spectrometric Analysis
2.12. Sample Preparation for Mass Spectrometry-Based Proteomics
2.13. High Efficiency Nanoflow Liquid Chromatography Electrospray-Ionization Coupled with Mass Spectrometry
2.14. Protein Identification and Quantification by Automated De Novo Sequencing (PEAKS Studio 8.0)
2.15. In Vivo Biodistribution Study of SSNs and Na-Glc-SSNs
2.16. 4T1.-Induced Mouse Model of Breast Cancer and Anti-Tumor Activity of siRNA-Loaded NPs
2.17. Statistical Analysis
3. Results and Discussion
3.1. Generation of SSNs and Evaluating Effects of NaCl and Glucose on Regulation of Particle Growth
3.2. Characterization of SSNs and Na-Glc-SSNs by Zeta Sizer
3.3. Characterization of Differently Formulated Particles by FE-SEM
3.4. Elemental Analysis of Nanoparticles by EDX
3.5. Characterization of SSNs and Na-Glc-SSNs by FT-IR and XRD
3.6. Acid Dissolution Profiles of SSNs and Na-Glc-SSNs
3.7. Assessment of Binding Affinity of siRNA to SSNs and Na-Glc-SSNs
3.8. Cellular Uptake of Fluorescence-Labeled siRNA Carried by Differently Formulated Strontium Sulfite Nanoparticles
3.9. Cell Viability Assessment with MTT Assay
3.10. Intracellular Delivery of EGFR and ROS1 siRNA Using SSNs and Na-Glc-SSNs
3.11. Analysis of Protein Corona Formed onto SSNs and Na-Glc-SSNs
3.12. In Vivo Biodistribution Study of SSNs and Na-Glc-SSNs
3.13. In Vivo Anti-Tumor Effect of ROS1 siRNA-Loaded SSNs and Na-Glc-SSNs
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Wong, J.K.; Mohseni, R.; Hamidieh, A.A.; MacLaren, R.E.; Habib, N.; Seifalian, A.M. Will nanotechnology bring new hope for gene delivery? Trends Biotechnol. 2017, 35, 434–451. [Google Scholar] [CrossRef] [PubMed]
- Karim, E.; Rosli, R.; H Chowdhury, E. Systemic delivery of nanoformulations of anti-cancer drugs with therapeutic potency in animal models of cancer. Curr. Cancer Ther. Rev. 2016, 12, 204–220. [Google Scholar] [CrossRef]
- Babu, A.; Muralidharan, R.; Amreddy, N.; Mehta, M.; Munshi, A.; Ramesh, R. Nanoparticles for sirna-based gene silencing in tumor therapy. IEEE Trans. Nanobiosci. 2016, 15, 849–863. [Google Scholar] [CrossRef] [PubMed]
- Karim, M.E.; Tha, K.K.; Othman, I.; Borhan Uddin, M.; Chowdhury, E.H. Therapeutic potency of nanoformulations of sirnas and shrnas in animal models of cancers. Pharmaceutics 2018, 10, 65. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, M.J.; Jain, R.K.; Langer, R. Engineering and physical sciences in oncology: Challenges and opportunities. Nat. Rev. Cancer 2017, 17, 659. [Google Scholar] [CrossRef] [PubMed]
- Lu, P.; Weaver, V.M.; Werb, Z. The extracellular matrix: A dynamic niche in cancer progression. J. Cell Biol. 2012, 196, 395–406. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jain, R.K. Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers. J. Clin. Oncol. 2013, 31, 2205–2218. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Coussens, L.M. Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer Cell 2012, 21, 309–322. [Google Scholar] [CrossRef] [PubMed]
- Sun, N.-F.; Liu, Z.-A.; Huang, W.-B.; Tian, A.-L.; Hu, S.-Y. The research of nanoparticles as gene vector for tumor gene therapy. Crit. Rev. Oncol./Hematol. 2014, 89, 352–357. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Z.; Liu, X.; Zhu, D.; Wang, Y.; Zhang, Z.; Zhou, X.; Qiu, N.; Chen, X.; Shen, Y. Nonviral cancer gene therapy: Delivery cascade and vector nanoproperty integration. Adv. Drug Deliv. Rev. 2017, 115, 115–154. [Google Scholar] [CrossRef] [PubMed]
- Mintzer, M.A.; Simanek, E.E. Nonviral vectors for gene delivery. Chem. Rev. 2008, 109, 259–302. [Google Scholar] [CrossRef] [PubMed]
- Loh, X.J.; Lee, T.-C.; Dou, Q.; Deen, G.R. Utilising inorganic nanocarriers for gene delivery. Biomater. Sci. 2016, 4, 70–86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mozar, F.S.; Chowdhury, E.H. Surface-modification of carbonate apatite nanoparticles enhances delivery and cytotoxicity of gemcitabine and anastrozole in breast cancer cells. Pharmaceutics 2017, 9, 21. [Google Scholar] [CrossRef] [PubMed]
- Murakami, T.; Tsuchida, K. Recent advances in inorganic nanoparticle-based drug delivery systems. Mini Rev. Med. Chem. 2008, 8, 175–183. [Google Scholar] [PubMed]
- Huang, H.-C.; Barua, S.; Sharma, G.; Dey, S.K.; Rege, K. Inorganic nanoparticles for cancer imaging and therapy. J. Control. Release 2011, 155, 344–357. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Du, J.; Liu, J.; Du, X.; Shen, S.; Zhu, Y.; Wang, X.; Ye, X.; Nie, S.; Wang, J. Smart Superstructures with Ultrahigh pH-Sensitivity for Targeting Acidic Tumor Microenvironment: Instantaneous Size Switching and Improved Tumor Penetration. ACS Nano 2016, 10, 6753–6761. [Google Scholar] [CrossRef] [PubMed]
- Li, H.-J.; Du, J.-Z.; Du, X.-J.; Xu, C.-F.; Sun, C.-Y.; Wang, H.-X.; Cao, Z.-T.; Yang, X.-Z.; Zhu, Y.-H.; Nie, S. Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy. Proc. Nat. Acad. Sci. USA 2016, 113, 4164–4169. [Google Scholar] [CrossRef]
- Ju, C.; Mo, R.; Xue, J.; Zhang, L.; Zhao, Z.; Xue, L.; Ping, Q.; Zhang, C. Sequential intra-intercellular nanoparticle delivery system for deep tumor penetration. Angew. Chem. Int. Ed. 2014, 53, 6253–6258. [Google Scholar] [CrossRef]
- Du, J.-Z.; Du, X.-J.; Mao, C.-Q.; Wang, J. Tailor-made dual ph-sensitive polymer–doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 2011, 133, 17560–17563. [Google Scholar] [CrossRef]
- Miao, L.; Wang, Y.; Lin, C.M.; Xiong, Y.; Chen, N.; Zhang, L.; Kim, W.Y.; Huang, L. Nanoparticle modulation of the tumor microenvironment enhances therapeutic efficacy of cisplatin. J. Control. Release 2015, 217, 27–41. [Google Scholar] [CrossRef] [Green Version]
- Xu, X.; Saw, P.E.; Tao, W.; Li, Y.; Ji, X.; Yu, M.; Mahmoudi, M.; Rasmussen, J.; Ayyash, D.; Zhou, Y. Tumor microenvironment-responsive multistaged nanoplatform for systemic rnai and cancer therapy. Nano Lett. 2017, 17, 4427–4435. [Google Scholar] [CrossRef] [PubMed]
- Helmlinger, G.; Sckell, A.; Dellian, M.; Forbes, N.S.; Jain, R.K. Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism. Clin. Cancer Res. 2002, 8, 1284–1291. [Google Scholar] [PubMed]
- Wojtkowiak, J.W.; Verduzco, D.; Schramm, K.J.; Gillies, R.J. Drug resistance and cellular adaptation to tumor acidic PH microenvironment. Mol. Pharm. 2011, 8, 2032–2038. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.; Grailer, J.J.; Pilla, S.; Steeber, D.A.; Gong, S. Tumor-targeting, ph-responsive, and stable unimolecular micelles as drug nanocarriers for targeted cancer therapy. Bioconjug. Chem. 2010, 21, 496–504. [Google Scholar] [CrossRef] [PubMed]
- Bae, Y.; Jang, W.-D.; Nishiyama, N.; Fukushima, S.; Kataoka, K. Multifunctional polymeric micelles with folate-mediated cancer cell targeting and PH-triggered drug releasing properties for active intracellular drug delivery. Mol. BioSyst. 2005, 1, 242–250. [Google Scholar] [CrossRef] [PubMed]
- Kim, I.-Y.; Kang, Y.-S.; Lee, D.S.; Park, H.-J.; Choi, E.-K.; Oh, Y.-K.; Son, H.-J.; Kim, J.-S. Antitumor activity of egfr targeted ph-sensitive immunoliposomes encapsulating gemcitabine in a549 xenograft nude mice. J. Control. Release 2009, 140, 55–60. [Google Scholar] [CrossRef] [PubMed]
- Deng, Z.; Zhen, Z.; Hu, X.; Wu, S.; Xu, Z.; Chu, P.K. Hollow chitosan–silica nanospheres as ph-sensitive targeted delivery carriers in breast cancer therapy. Biomaterials 2011, 32, 4976–4986. [Google Scholar] [CrossRef] [PubMed]
- Shen, M.; Huang, Y.; Han, L.; Qin, J.; Fang, X.; Wang, J.; Yang, V.C. Multifunctional drug delivery system for targeting tumor and its acidic microenvironment. J. Control. Release 2012, 161, 884–892. [Google Scholar] [CrossRef] [PubMed]
- Chowdhury, E.H. Ph-responsive magnesium-and carbonate-substituted apatite nano-crystals for efficient and cell-targeted delivery of transgenes. Open J. Genet. 2013, 3, 38. [Google Scholar] [CrossRef]
- Chua, M.; Tiash, S.; Fatemian, T.; Noordin, M.; Keng, C.; Chowdhury, E. Carbonate apatite-facilitated intracellular delivery of c-ros1 small interfering rna sensitises mcf-7 breast cancer cells to cisplatin and paclitaxel. OA Cancer 2013, 1. [Google Scholar] [CrossRef]
- Tada, S.; Chowdhury, E.H.; Cho, C.-S.; Akaike, T. Ph-sensitive carbonate apatite as an intracellular protein transporter. Biomaterials 2010, 31, 1453–1459. [Google Scholar] [CrossRef] [PubMed]
- Tiash, S.; Kamaruzman, N.I.B.; Chowdhury, E.H. Carbonate apatite nanoparticles carry sirna (s) targeting growth factor receptor genes egfr1 and erbb2 to regress mouse breast tumor. Drug Deliv. 2017, 24, 1721–1730. [Google Scholar] [CrossRef] [PubMed]
- Uddin, M.B.; Balaravi Pillai, B.; Tha, K.K.; Ashaie, M.; Karim, M.E.; Chowdhury, E.H. Carbonate apatite nanoparticles-facilitated intracellular delivery of sirna (s) targeting calcium ion channels efficiently kills breast cancer cells. Toxics 2018, 6, 34. [Google Scholar] [CrossRef] [PubMed]
- Shaw, A.T.; Ou, S.-H.I.; Bang, Y.-J.; Camidge, D.R.; Solomon, B.J.; Salgia, R.; Riely, G.J.; Varella-Garcia, M.; Shapiro, G.I.; Costa, D.B. Crizotinib in ros1-rearranged non–small-cell lung cancer. N. Engl. J. Med. 2014, 371, 1963–1971. [Google Scholar] [CrossRef] [PubMed]
- Eom, M.; Lkhagvadorj, S.; Oh, S.S.; Han, A.; Park, K.H. Ros1 expression in invasive ductal carcinoma of the breast related to proliferation activity. Yonsei Med. J. 2013, 54, 650–657. [Google Scholar] [CrossRef] [PubMed]
- Eccles, S.A. The epidermal growth factor receptor/erb-b/her family in normal and malignant breast biology. Int. J. Dev. Biol. 2011, 55, 685–696. [Google Scholar] [CrossRef] [PubMed]
- Bhargava, R.; Gerald, W.L.; Li, A.R.; Pan, Q.; Lal, P.; Ladanyi, M.; Chen, B. Egfr gene amplification in breast cancer: Correlation with epidermal growth factor receptor mrna and protein expression and her-2 status and absence of egfr-activating mutations. Mod. Pathol. 2005, 18, 1027. [Google Scholar] [CrossRef]
- Weber, F.; Fukino, K.; Sawada, T.; Williams, N.; Sweet, K.; Brena, R.; Plass, C.; Caldes, T.; Mutter, G.; Villalona-Calero, M. Variability in organ-specific egfr mutational spectra in tumour epithelium and stroma may be the biological basis for differential responses to tyrosine kinase inhibitors. Br. J. Cancer 2005, 92, 1922. [Google Scholar] [CrossRef]
- Qian, W.-Y.; Sun, D.-M.; Zhu, R.-R.; Du, X.-L.; Liu, H.; Wang, S.-L. Ph-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release. Int. J. Nanomed. 2012, 7, 5781. [Google Scholar]
- Miele, E.; Spinelli, G.P.; Miele, E.; Di Fabrizio, E.; Ferretti, E.; Tomao, S.; Gulino, A. Nanoparticle-based delivery of small interfering rna: Challenges for cancer therapy. Int. J. Nanomed. 2012, 7, 3637. [Google Scholar]
- Wisse, E.; Jacobs, F.; Topal, B.; Frederik, P.; De Geest, B. The size of endothelial fenestrae in human liver sinusoids: Implications for hepatocyte-directed gene transfer. Gene Ther. 2008, 15, 1193. [Google Scholar] [CrossRef] [PubMed]
- Aird, W.C. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ. Res. 2007, 100, 158–173. [Google Scholar] [CrossRef] [PubMed]
- Kanasty, R.; Dorkin, J.R.; Vegas, A.; Anderson, D. Delivery materials for sirna therapeutics. Nat. Mater. 2013, 12, 967. [Google Scholar] [CrossRef] [PubMed]
- Davis, M.E.; Shin, D.M. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat. Rev. Drug Discov. 2008, 7, 771. [Google Scholar] [CrossRef]
- Yarden, Y. The egfr family and its ligands in human cancer: Signalling mechanisms and therapeutic opportunities. Eur. J. Cancer 2001, 37, 3–8. [Google Scholar] [CrossRef]
- Tiash, S.; Chua, M.J.; Chowdhury, E.H. Knockdown of ros1 gene sensitizes breast tumor growth to doxorubicin in a syngeneic mouse model. Int. J. Oncol. 2016, 48, 2359–2366. [Google Scholar] [CrossRef] [PubMed]
- Trent, J.M.; Rosenfeld, S.B.; Meyskens, F.L. Chromosome 6q involvement in human malignant melanoma. Cancer Genet. Cytogenet. 1983, 9, 177–180. [Google Scholar] [CrossRef]
- Watkins, D.; Dion, F.; Poisson, M.; Delattre, J.-Y.; Rouleau, G.A. Analysis of oncogene expression in primary human gliomas: Evidence for increased expression of the ros oncogene. Cancer Genet. Cytogenet. 1994, 72, 130–136. [Google Scholar] [CrossRef]
- Rikova, K.; Guo, A.; Zeng, Q.; Possemato, A.; Yu, J.; Haack, H.; Nardone, J.; Lee, K.; Reeves, C.; Li, Y. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007, 131, 1190–1203. [Google Scholar] [CrossRef] [PubMed]
- Eom, M.; Han, A.; Yi, S.Y.; Shin, J.J.; Cui, Y.; Park, K.H. Rheb expression in fibroadenomas of the breast. Pathol. Int. 2008, 58, 226–232. [Google Scholar] [CrossRef]
- Hashizume, H.; Baluk, P.; Morikawa, S.; McLean, J.W.; Thurston, G.; Roberge, S.; Jain, R.K.; McDonald, D.M. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 2000, 156, 1363–1380. [Google Scholar] [CrossRef]
Protein Classes | Identified Proteins | −10lgP | Coverage | Mass | Function |
---|---|---|---|---|---|
Transport proteins | Albumin 1 | 156.86 | 31 | 68,693 | chaperone binding, DNA binding, fatty acid binding, identical protein binding, oxygen binding, pyridoxal phosphate binding and toxic substance binding |
Enzymes | Glutamine synthetase | 38.65 | 4 | 42,019 | glutamine biosynthetic process |
Structural proteins | Keratin 16 | 32.67 | 1 | 51,606 | structural constituent of cytoskeleton |
Structural proteins | Keratin 16 | 32.67 | 1 | 51,693 | structural molecule activity |
Structural proteins | Keratin intermediate filament 16b | 32.67 | 1 | 51,966 | structural molecule activity |
Structural proteins | Keratin intermediate filament 16a | 32.67 | 1 | 52,053 | structural molecule activity |
Structural proteins | Uncharacterized protein | 24.55 | 2 | 33,882 | structural molecule activity |
Structural proteins | Keratin 24 variant 2 | 24.55 | 2 | 40,994 | structural molecule activity |
Structural proteins | Keratin 19 | 24.55 | 2 | 44,542 | protein-containing complex binding, structural constituent of muscle |
Structural proteins | Keratin, type I cuticular Ha2 | 24.55 | 2 | 51,153 | structural molecule activity |
Structural proteins | Keratin 15, isoform CRA_a | 24.55 | 2 | 49,494 | scaffold protein binding, structural molecule activity |
Structural proteins | Keratin, type I cytoskeletal 10 | 24.55 | 1 | 57,041 | protein heterodimerization activity, structural constituent of epidermis |
Structural proteins | Nup205 | 23.83 | 1 | 69,494 | structural constituent of nuclear pore |
Transport Proteins | Conserved oligomeric Golgi complex subunit 7 | 23.83 | 1 | 80,582 | intracellular protein transport |
Transport Proteins | Conserved oligomeric Golgi complex subunit 7 | 23.83 | 1 | 86,075 | intracellular protein transport |
Enzymes | Ercc5 protein | 22.76 | 1 | 86,901 | endonuclease activity, single-stranded DNA binding |
Enzymes | Nek1 protein | 21.82 | 2 | 48,636 | ATP binding, protein serine/threonine kinase activity |
Enzymes | Nek1 protein | 21.82 | 1 | 133,856 | ATP binding, protein kinase activity |
Enzymes | Nek1 protein | 21.82 | 1 | 139,659 | ATP binding, protein kinase activity |
Enzymes | MKIAA1901 protein | 21.82 | 1 | 139,947 | ATP binding, protein kinase activity |
Enzymes | Nek1 protein | 21.82 | 1 | 144,269 | ATP binding, protein kinase activity |
others | WD repeat-containing protein 81 | 21.82 | 1 | 211,931 | mitochondrion organization |
Protein Classes | Identified Proteins | −10lgP | Coverage (%) | Mass | Functions |
---|---|---|---|---|---|
Structural proteins | Keratin, type I cytoskeletal 10 | 127.77 | 22 | 57,041 | Protein heterodimerization activity, structural constituent of epidermis. |
Structural proteins | Keratin, type II cytoskeletal 6B | 112.44 | 9 | 59,526 | structural molecule activity |
Structural proteins | Krt6b protein | 112.44 | 9 | 60,191 | structural molecule activity |
Structural proteins | Krt6b protein | 112.44 | 9 | 60,273 | structural molecule activity |
Structural proteins | Keratin 77 | 106.07 | 6 | 61,302 | structural molecule activity |
Structural proteins | Keratin 77 | 106.07 | 6 | 61,359 | structural molecule activity |
Structural proteins | Keratin Kb40 | 69.48 | 2 | 85,239 | structural molecule activity |
Structural proteins | Keratin 78 | 69.48 | 1 | 112,265 | structural molecule activity |
Structural proteins | Type II cytokeratin Kb40 | 69.03 | 3 | 47,619 | structural molecule activity |
Structural proteins | Krt78 protein | 63.78 | 3 | 54,765 | structural molecule activity |
Structural proteins | Krt78 protein | 63.78 | 3 | 56,780 | structural molecule activity |
Structural proteins | Krt78 protein | 63.78 | 3 | 54,774 | structural molecule activity |
Structural proteins | Keratin 15, isoform CRA_a | 68.25 | 4 | 49,494 | scaffold protein binding, structural molecule activity |
Structural proteins | Uncharacterized protein | 47.85 | 2 | 58,266 | structural molecule activity |
Structural proteins | Uncharacterized protein | 47.85 | 2 | 58,240 | structural molecule activity |
Structural proteins | Keratin 90 | 47.85 | 2 | 58,224 | structural molecule activity |
Structural proteins | Krt2 protein | 42.78 | 1 | 70,923 | structural molecule activity |
Enzymes | Eif4a1 | 29.17 | 3 | 33,069 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eukaryotic initiation factor 4A-II | 29.17 | 3 | 36,166 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eukaryotic initiation factor 4A-II | 29.17 | 2 | 41,290 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eif4a1 | 29.17 | 2 | 41,491 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eif4a1 protein | 29.17 | 2 | 46,023 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eif4a1 | 29.17 | 2 | 46,184 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eif4a1 | 29.17 | 2 | 46,140 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eif4a1 | 29.17 | 2 | 46,154 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
Enzymes | Eukaryotic translation initiation factor 4A2 | 29.17 | 2 | 46,402 | ATP binding, ATP-dependent RNA helicase activity, translation initiation factor activity |
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Karim, M.E.; Shetty, J.; Islam, R.A.; Kaiser, A.; Bakhtiar, A.; Chowdhury, E.H. Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells. Pharmaceutics 2019, 11, 89. https://doi.org/10.3390/pharmaceutics11020089
Karim ME, Shetty J, Islam RA, Kaiser A, Bakhtiar A, Chowdhury EH. Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells. Pharmaceutics. 2019; 11(2):89. https://doi.org/10.3390/pharmaceutics11020089
Chicago/Turabian StyleKarim, Md. Emranul, Jayalaxmi Shetty, Rowshan Ara Islam, Ahsanul Kaiser, Athirah Bakhtiar, and Ezharul Hoque Chowdhury. 2019. "Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells" Pharmaceutics 11, no. 2: 89. https://doi.org/10.3390/pharmaceutics11020089
APA StyleKarim, M. E., Shetty, J., Islam, R. A., Kaiser, A., Bakhtiar, A., & Chowdhury, E. H. (2019). Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells. Pharmaceutics, 11(2), 89. https://doi.org/10.3390/pharmaceutics11020089