Nanocarrier Based Approach for Systematic Delivery of Small Interfering-RNA for Treatment of Cancer
Keywords:
Nanocarriers, RNAi, miRNA, siRNA, Gene delivery, Gene silencingAbstract
Nanomedicine is an increasing science area concerned with the development and fabrication of nanometer-scale structures for improved cancer care, detection, and imaging. Most cancer treatment options available in the clinic currently limit their usages with limited solubility and off-target side effects. Nanomaterials improve the bioavailability, solubility, selective organ distribution, and therapeutic effect of several biomolecules. Gene therapy using free nucleic acids can deal with vital candidate genes of cancer. However, their effect is delayed due to poor cell uptake and instability in circulation. Recently, Short interfering RNA (siRNA), highly capable of knockdown of specific genes, has emerged as a promising molecular therapeutic tool in targeted cancer
treatment. Using liposomes, polymers, and dendrimers nanoparticles to deliver cancer drugs and siRNAs have been successful in recent preclinical studies. However, improving the tumor specificity of therapeutic cargo remains a major challenge. Therefore, the development of a novel tumor-targeted drug/gene delivery platform is urgently needed. Numerous novel drug delivery devices for siRNA distribution were being created to address the main challenges preventing siRNA’s therapeutic potential. In the present review, we summarise the recent advancements in the nano-based drug delivery systems for siRNA delivery. Additionally, the innovative nanomedicines used for cancer therapy would be addressed. This study comprises a vast variety of siRNA drug delivery systems established in vitro and in vivo for improved intracellular delivery and selective gene regulation and addresses their features and possibilities for functional siRNA medical applications
References
The global challenge of cancer, Nat Cancer 1 (2020): 1-2.
Siegel RL, Miller KD, Jemal A. “Cancer statistics”. CA: A Cancer Journal for Clin 70 (2020):7-30.
Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, et al. “Cancer treatment and survivorship statistics”. CA: A Cancer J Clin 69 (2019): 363-385.
Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, et al. “Molecular mechanisms and biological functions of siRNA”. Int J Biomed Sci 13 (2017): 48-57.
Chernikov IV, Vlassov VV, Chernolovskaya EL. “Current development of siRNA bioconjugates: from research to the clinic”. Front Pharmacol 10 (2019).
Hu B, Weng Y, Xia XH, Liang XJ, Huang Y. “Clinical advances of siRNA therapeutics”. J Gene Med 21(2019): e3097.
Oh YK, Park TG. “siRNA delivery systems for cancer treatment”. Adv Drug Del rev 61(2009): 850-862.
Raja MAG, Katas H, Amjad MW. “Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA”. Asian J Pharmaceutical Sci 14 (2019): 497-510.
Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, et al. “Analysis of nanoparticle delivery to tumours”. Nature Reviews Materials 1 (2016): 16014.
Thomas OS, Weber W. “Overcoming physiological barriers to nanoparticle delivery—are we there yet?”. Front Bioeng Biotech 7 (2019).
Wang AZ, Langer R, Farokhzad OC. “Nanoparticle delivery of cancer drugs”. Annual review of medicine 63 (2012): 185-198.
Ventola CL. “The nanomedicine revolution: part 2: current and future clinical applications”. P T 37 (2012): 582-591.
El-Sayed A, Kamel M. “Advances in nanomedical applications: diagnostic, therapeutic, immunization, and vaccine production”. Environmental Science and Pollution Research 27 (2020): 19200-19213.
Nichols JW, Bae YH. “EPR: Evidence and fallacy”. J Controlled Release 190 (2014): 451-464.
Wei Y, Quan L, Zhou C, Zhan Q. “Factors relating to the biodistribution & clearance of nanoparticles & their effects on in vivo application”. Nanomedicine 13 (2018): 1495-1512.
Mahapatro A, Singh DK. “Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines”. J Nanobiotechnol 9 (2011): 55.
Salah E, Abouelfetouh MM, Pan Y, Chen D, Xie S. “Solid lipid nanoparticles for enhanced oral absorption: A review”. Colloids and Surfaces B: Biointerfaces (2020): 111305.
Puligundla P, Mok C, Ko S, Liang J, Recharla N. “Nanotechnological approaches to enhance the bioavailability and therapeutic efficacy of green tea polyphenols”. J Functional Foods 34 (2017): 139-151.
Roberts TC, Langer R, Wood MJA. “Advances in oligonucleotide drug delivery”. Nature Reviews Drug Disc 19 (2020): 673-694.
Xu CF, Wang J. “Delivery systems for siRNA drug development in cancer therapy”. Asian J Pharmaceutical Sciences 10(1) (2015): 1-12.
Subhan XA, Torchilin VP. “Efficient nanocarriers of siRNA therapeutics for cancer treatment”. Transl Res 214 (2019): 62- 91.
Elbashir SM, Lendeckel W, Tuschl T. “RNA interference is mediated by 21-and 22-nucleotide RNAs”. Genes Development 15 (2001): 188-200.
Turner JJ, Jones SW, Moschos SA, Lindsay MA, Gait MJ. “MALDI-TOF mass spectral analysis of siRNA degradation in serum confirms an RNAse A-like activity”. Molecular BioSystems 3(2006): 43-50.
Chen M, Du Q, Zhang HY, Wahlestedt C, Liang Z. “Vectorbased siRNA delivery strategies for high-throughput screening of novel target genes.” J RNAi and Gene Silencing: An International J RNA and Gene Targeting Research 1 (2005): 5.
Sakurai F, Kawabata K, Koizumi N. “Adenovirus vectormediated doxycycline-inducible RNA interference.” Gene Therapy 13 (2006): 1118-1126.
Lee NS, Dohjima T, Bauer G, Li H, Li MJ, et al. “Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells”. Nature biotechnology 20 (2002): 500-505.
Gao Y, Liu XL, Li XR. Research progress on siRNA delivery with nonviral carriers”. International journal of nanomedicine 6 (2011): 1017.
Lee JM, Yoon TJ, Cho YS. “Recent developments in nanoparticle-based siRNA delivery for cancer therapy”. BioMed research international 2013 (2013).
Lankalapalli S, Kolapalli VRM. “Polyelectrolyte complexes: A review of their applicability in drug delivery technology”. Indian J Pharm Sci 71 (2009): 481-487.
Thomas M, Klibanov A. “Non-viral gene therapy: polycationmediated DNA delivery”. Applied microbiology and biotechnology 62 (2003): 27-34.
Kwok A, Hart SL. “Comparative structural and functional studies of nanoparticle formulations for DNA and siRNA delivery”. Nanomedicine: Nanotechnology, Biology and Medicine 7 (2011): 210-219.
Park TG, Jeong JH, Kim SW. “Current status of polymeric gene delivery systems”. Advanced drug delivery reviews 58 (2006): 467-486.
Gary DJ, Puri N, Won YY. “Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery”. J Controlled Release 121(1-2) (2007): 64-73.
Peng Q, Zhong Z, Zhuo R. “Disulfide cross-linked polyethylenimines (PEI) prepared via thiolation of low molecular weight PEI as highly efficient gene vectors”. Bioconjugate chemistry 19 (2008): 499-506.
Hoelder S, Clarke PA, Workman P. “Discovery of small molecule cancer drugs: successes, challenges and opportunities”. Mol Oncol 6 (2012): 155-176.
Nurgali K, Jagoe RT, Abalo R. “Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae?”. Front Pharmacol 9 (2018): 245-245.
Sever R, Brugge JS. “Signal transduction in cancer”. Cold Spring Harb Perspect Med 5 (2015): a006098.
Bayat Mokhtari R, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B. “Combination therapy in combating cancer”. Oncotarget 8 (2017): 38022-38043.
Chalbatani GM, Dana H, Gharagouzloo E, Grijalvo S, Eritja R, et al. “Small interfering RNAs (siRNAs) in cancer therapy: a nano-based approach”. Int j Nanomedicine 14 (2019): 3111.
Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, et al. “Therapeutic siRNA: state of the art”. Signal Transduct Target Ther 5 (2020): 1-25.
Yu AM, Choi YH, Tu MJ. “RNA Drugs and RNA targets for small molecules: principles, progress, and challenges”. Pharmacol Rev 72 (2020): 862-898.
Chery J. “RNA therapeutics: RNAi and antisense mechanisms and clinical applications”. Postdoc J 4 (2016): 35-50.
Hocine S, Singer RH, Grünwald D. “RNA processing and export”. Cold Spring Harb Perspect Biol 2 (2010): a000752-a000752.
Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK. “RNA interference in the clinic: challenges and future directions”. Nat Rev Can 11 (2011): 59-67.
Aagaard L, Rossi JJ. “RNAi therapeutics: principles, prospects and challenges”. Advan Drug Delivery Reviews 59 (2007): 75- 86.
Ozcan G, Ozpolat B, Coleman RL, Sood AK, Lopez-Berestein G. “Preclinical and clinical development of siRNA-based therapeutics”. Advan Drug Delivery Reviews 87 (2015): 108-119.
Sajid MI, Moazzam M, Kato S, Yeseom Cho K, Tiwari RK. “Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside”. Pharmaceuticals 13 (2020): 294.
Yonezawa S, Koide H, Asai T. “Recent advances in siRNA delivery mediated by lipid-based nanoparticles”. Adv Drug Deliv Rev (2020).
Mohammadinejad R, Dehshahri A, Madamsetty VS, Zahmatkeshan M, Tavakol S,et al. “In vivo gene delivery mediated by non-viral vectors for cancer therapy”. J Control Release 325 (2020): 249-275.
Kanasty R, Dorkin JR, Vegas A, Anderson D. “Delivery materials for siRNA therapeutics”. Nature mat 12 (2013): 967-977.
Subhan MA, TorchilinV. “Efficient nanocarriers of siRNA therapeutics for cancer treatment”. Translational Research 214 (2019): 62-91.
Johannes L, Lucchino M. “Current challenges in delivery and cytosolic translocation of therapeutic RNAs”. Nucleic Acid Ther 28 (2018): 178-193.
Bhatia S. “Nanoparticles types, classification, characterization, fabrication methods and drug delivery applications”. Natural polymer drug delivery systems, Springer (2016):33-93.
Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG. “Non-viral vectors for gene-based therapy”. Nat Rev Genet 15 (2014): 541-555.
Yalcin E, Kara G, Celik E, Pinarli FA, Saylam G, Sucularli C, et al. “Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment”. Preparative Biochemistry and Biotechnology 49 (2019): 659-670.
Büyükköroαlu G, αenel B, Yenilmez E. “Vaginal suppositories with siRNA and paclitaxel-incorporated solid lipid nanoparticles for cervical cancer: Preparation and in vitro evaluation”. RNA Interference and Cancer Therapy, Springer (2019): 303-328.
Arami S, Mahdavi M, Rashidi MR, Yekta R, Rahnamay M, et al. “Apoptosis induction activity and molecular docking studies of survivin siRNA carried by Fe3O4-PEG-LAC-chitosan-PEI nanoparticles in MCF-7 human breast cancer cells”. J Pharm Biomed Anal 142 (2017): 145-154.
Murata N, Takashima Y, Toyoshima K, Yamamoto M, Okada H. “Anti-tumor effects of anti-VEGF siRNA encapsulated with PLGA microspheres in mice”. J Control Release 126 (2008): 246-54.
Li J, Liang H, Liu J, Wang Z. “Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy”. Int J Pharm 546 (2018): 215-225.
Luong D, Kesharwani P, Deshmukh R, Mohd Amin MCI, Gupta U, et al. “PEGylated PAMAM dendrimers: enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery”. Acta Biomaterialia 43 (2016): 14-29.
Liu X, Peng L. “Dendrimer nanovectors for SiRNA delivery”. Methods Mol Biol 1364 (2016): 127-42.
Abedi-Gaballu F, Dehghan G, Ghaffari M, Yekta R, Abbaspour- Ravasjani S, et al. “PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy”. Appl Mater Today 12 (2018): 177-190.
Liu C, Liu X, Rocchi P, Qu F, Iovanna JL, Peng L. “Arginineterminated generation 4 PAMAM dendrimer as an effective nanovector for functional siRNA delivery in vitro and in vivo”. Bioconjug Chem 25 (2014): 521-32.
Bohr A, Tsapis N, Foged C, Andreana I, Yang M, Fattal E. “Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model”. European J Pharmaceutics and Biopharmaceutics 156 (2020): 114-120.
Li T, Chen Q, Zheng Y, Zhang P, Chen X, Lu J, et al. “ PAMAM- cRGD mediating efficient siRNA delivery to spermatogonial stem cells”. Stem Cell Res Ther10 (2019): 399.
Cai X, Zhu H, Zhang Y, Gu Z. “Highly efficient and safe delivery of VEGF siRNA by bioreducible fluorinated peptide dendrimers for cancer therapy”. ACS Applied Materials & Interfaces 9(11) (2017): 9402-9415.
Ghaffari M, Dehghan G, Baradaran B, Zarebkohan A, Mansoori B, Soleymani J, Ezzati Nazhad Dolatabadi J, et al. “Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells”. Colloids Surf B Biointerfaces 188 (2020): 110762.
Dong Y, Yu T, Ding L, Laurini E, Huang Y, et al. “A dual targeting dendrimer-mediated siRNA delivery system for effective gene silencing in cancer therapy”. J American Chemical Society 140 (2018): 16264-16274.
Osman G, Rodriguez J, Chan SY, Chisholm J, Duncan G, Kim N, et al. “PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy”. J Controlled Release 285 (2018): 35-45.
Wang J, Li S, Han Y, Guan J, Chung S, Wang C, Li D. “Poly (Ethylene Glycol)–polylactide micelles for cancer therapy”. Front Pharmacol 9 (2018): 202.
Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. “PEG conjugated VEGF siRNA for anti-angiogenic gene therapy”. J Control Release 116 (2006): 123-9.
Choi SW, Lee SH, Mok H, Park TG. “Multifunctional siRNA delivery system: polyelectrolyte complex micelles of six-arm PEG conjugate of siRNA and cell penetrating peptide with crosslinked fusogenic peptide”. Biotechnol Prog 26 (2010): 57- 63.
Khan AA, Alanazi AM, Jabeen M, Chauhan A, Ansari MA. “Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice”. Sci Rep 9 (2019): 15825-15825.
Lee SH, Lee JY, Kim JS, Park TG, Mok H. “Amphiphilic siRNA Conjugates for Co-Delivery of Nucleic Acids and Hydrophobic Drugs”. Bioconjug Chem 28 (2017): 2051-2061.
Wen ZM, Jie J, Zhang Y, Liu H, Peng LP. “A self-assembled polyjuglanin nanoparticle loaded with doxorubicin and anti- Kras siRNA for attenuating multidrug resistance in human lung cancer”. Biochem Biophys Res Commun 493 (2017): 1430-1437.
Kang J, Joo J, Kwon EJ, Skalak M, Hussain S, She ZG, et al. “Selfsealing porous silicon-calcium silicate core–shell nanoparticles for targeted siRNA delivery to the injured brain”. Adv Mater 28 (2016): 7962-7969.
Lee SH, Lee JY, Kim JS, Park TG, Mok H. “Amphiphilic siRNA conjugates for co-delivery of nucleic acids and hydrophobic drugs”. Bioconjugate Chemistry 28 (2017): 2051-2061.
Gaziova Z, Baumann V, Winkler AM, Winkler J. “Chemically defined polyethylene glycol siRNA conjugates with enhanced gene silencing effect”. Bioorg Med Chem 22 (2014): 2320-2326.
Kim HK, Davaa E, Myung CS, Park JS. “Enhanced siRNA delivery using cationic liposomes with new polyarginineconjugated PEG-lipid”. International J Pharmaceutics 392 (2010): 141-147.
Aldrian G, Vaissière A, Konate K, Seisel Q, Vivès E, Fernandez F, et al. “PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo”. J Control Release 256 (2017): 79-91.
Ngamcherdtrakul W, Sangvanich T, Reda M, Gu S, Bejan D, Yantasee W. “Lyophilization and stability of antibodyconjugated mesoporous silica nanoparticle with cationic polymer and PEG for siRNA delivery” International Journal of Nanomedicine 13 (2018): 4015-4027.
Khalil IA, Yamada Y, Harashima H. “Optimization of siRNA delivery to target sites: issues and future directions”. Expert Opin Drug Deliv15 (2018): 1053-1065.
Hattori Y, Tamaki K, Sakasai S, Ozaki KI, Onishi H. “Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene-silencing effects and siRNA biodistribution in mice”. Mol Med Rep 22 (2020): 4183-4196.
Amjad MW, Kesharwani P, Mohd Amin MCI, Iyer AK. “Recent advances in the design, development, and targeting mechanisms of polymeric micelles for delivery of siRNA in cancer therapy”. Progress in Polymer Science 64 (2017): 154- 181.
Li S, Omi M, Cartieri F, Konkolewicz D, Mao G, Gao H, et al. “Cationic hyperbranched polymers with biocompatible shells for siRNA delivery”. Biomacromolecules 19 (2018): 3754-3765.
Nothisen M, Kotera M, Voirin E, Remy JS, Behr JP. “Cationic siRNAs Provide carrier-free gene silencing in animal cells”. Journal of the American Chemical Society 131 (2009): 17730- 17731.
Perche P, Nothisen M, Bagilet J, Behr JP, Kotera M, Remy JS. “Cell-penetrating cationic siRNA and lipophilic derivatives efficient at nanomolar concentrations in the presence of serum and albumin”. J Control Release 170 (2013): 92-8.
Hong CA, Nam YS. “Functional nanostructures for effective delivery of small interfering RNA Therapeutics”. Theranostics 4 (2014): 1211-1232.
Rozema DB, Lewis DL, Wakefield DH, Wong SC, Klein JJ. “Dynamic polyconjugates for targeted in vivo delivery of siRNA to hepatocytes”. Proc Natl Acad Sci USA 104 (2007): 12982-7.
Meyer M, Dohmen C, Philipp A, Kiener D, Maiwald D, et al. “Synthesis and biological evaluation of a bioresponsive and endosomolytic siRNAαpolymer conjugate”. Mol Pharmaceutics 6 (2009): 752-762.
Zhao L, Gu C, Gan Y, Shao L, Chen H, Zhu H. “Exosomemediated siRNA delivery to suppress postoperative breast cancer metastasis”. J Control Release 318 (2020): 1-15.
Hemati M, Haghiralsadat F, Yazdian F, Jafari F, Moradi A, Malekpour-Dehkordi Z. “Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy”. Artif Cells Nanomed Biotechnol 47 (2019): 1295-1311.
Liu W, Dai J, Xue W. “Design and self-assembly of albumin nanoclusters as a dynamic-covalent targeting co-delivery and stimuli-responsive controlled release platform”. J Mater Chem B 6(42) (2018): 6817-6830.
Sun X, Chen Y, Zhao H, Qiao G, Liu M, Zhang C, Cui D, Ma L. “Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma”. Drug Deliv 25 (2018): 1718-1727.
Singha K, Namgung R, Kim WJ. “Polymers in small-interfering RNA delivery”. Nucleic acid Ther 21 (2011): 133-147.
Lam JKW, Chow MYT, Zhang Y, Leung SWS. “siRNA versus miRNA as therapeutics for gene silencing”. Mol Ther Nucleic Acids 4 (2015): e252-e252.
Makadia HK, Siegel SJ. “Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable controlled drug delivery carrier”. Polymers (Basel) 3 (2011): 1377-1397.
Kapoor DN, Bhatia A, Kaur R, Sharma R, Kaur G, Dhawan S. “PLGA: a unique polymer for drug delivery”. Ther Deliv 6 (2015): 41-58.
Wahane A, Waghmode A, Kapphahn A, Dhuri K, Gupta A, Bahal R. “Role of lipid-based and polymer-based nonviral vectors in nucleic acid delivery for next-generation gene therapy”. Molecules 25 (2020).
Harrison EB, Azam SH, Pecot CV. “Targeting accessories to the crime: nanoparticle nucleic acid delivery to the tumor microenvironment”. Front Pharmacol 9 (2018).
Lee JM, Yoon TJ, Cho YS. “Recent developments in nanoparticle-based siRNA delivery for cancer therapy”. BioMed Research International (2013): 782041.
Samaridou E, Heyes J, Lutwyche P. “Lipid nanoparticles for nucleic acid delivery: Current perspectives”. Adv Drug Delivery Rev (2020):37-63.
Lee SH, Mok H, Lee Y, Park TG. “Self-assembled siRNA- PLGA conjugate micelles for gene silencing”. J Control Release 152 (2011): 152-8.
Sung YK, Kim SW. “Recent advances in polymeric drug delivery systems”. Biomaterials Research 24 (2020): 12.
Xiao Y, Shi K, Qu Y, Chu B, Qian Z. “Engineering nanoparticles for targeted delivery of nucleic acid therapeutics in tumor”. Molecular Therapy - Methods & Clinical Development 12 (2019): 1-18.
Luly KM, Choi J, Rui Y, Green JJ, Jackson EM. “Safety considerations for nanoparticle gene delivery in pediatric brain tumors”. Nanomedicine 15 (2020): 1805-1815.
Byeon Y, Lee JW, Choi WS, Won JE, Kim GH, et al. “CD44- targeting PLGA nanoparticles incorporating paclitaxel and FAK siRNA overcome chemoresistance in epithelial ovarian cancer”. Cancer Res 78 (2018): 6247-6256.
αenel B, Öztürk AA. “New approaches to tumor therapy with siRNA-decorated and chitosan-modified PLGA nanoparticles”. Drug Dev Ind Pharm 45 (2019): 1835-1848.
Hazekawa M, Nishinakagawa T, Kawakubo-Yasukochi T, Nakashima M. “Therapeutic effect of Glypican-3 gene silencing for ovarian cancer using siRNA-PLGA hybrid micelles in a murine peritoneal dissemination model”. Journal of Pharmacological Sciences 139 (2019): 231-239.
Kwak SY, Lee S, Han HD, Chang S, Kim KP, Ahn HJ. “PLGA nanoparticles codelivering siRNAs against programmed cell death protein-1 and its ligand gene for suppression of colon tumor growth”. Mol Pharm 16 (2019): 4940-4953.
Kumar P, Ban HS, Kim SS, Wu H, Pearson T, et al. “T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice”. Cell 134 (2008): 577-86.
Dinis Ano Bom AP, da Costa Neves PC, Bonacossa de Almeida CE, Silva D, Missailidis S. “Aptamers as delivery agents of siRNA and chimeric formulations for the treatment of cancer”. Pharmaceutics 11 (2019): 684.
Sivakumar P, Kim S, Kang HC, Shim MS. “Targeted siRNA delivery using aptamer-siRNA chimeras and aptamerconjugated nanoparticles”. Wiley Interdiscip Rev Nanomed Nanobiotechnol 11 (2019): e1543.
Esposito CL, Nuzzo S, Catuogno S, Romano S, de Nigris F, et al. “STAT3 gene silencing by aptamer-siRNA chimera as selective therapeutic for glioblastoma”. Mol Ther Nucleic Acids 10 (2018): 398-411.
Guo P, Coban O, Snead NM, Trebley J, Hoeprich S, et al. “Engineering RNA for targeted siRNA delivery and medical application”. Adv Drug Deliv rev 62 (2010): 650-666.
Munyendo WL, Lv H, Benza-Ingoula H, Baraza LD, Zhou J. “Cell penetrating peptides in the delivery of biopharmaceuticals”. Biomolecules 2 (2012): 187-202.
Taylor RE, Zahid M. “Cell penetrating peptides, novel vectors for gene therapy”. Pharmaceutics 12 (2020).
Moschos SA, Jones SW, Perry MM, Williams AE, Erjefalt JS, et al. “Lung delivery studies using siRNA conjugated to TAT(48- 60) and penetratin reveal peptide induced reduction in gene expression and induction of innate immunity”. Bioconjug Chem 18 (2007): 1450-9.
Tai W. “Current aspects of siRNA bioconjugate for in vitro and in vivo delivery”. Molecules (Basel, Switzerland) 24 (2019): 2211.
Habault J, Poyet JL. “Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies”. Molecules 24 (2019).
Gagat M, Zieliαska W, Grzanka A. “Cell-penetrating peptides and their utility in genome function modifications (Review)”. Int J Mol Med 40 (2017): 1615-1623.
Järver P, Coursindel T, Andaloussi SEL, Godfrey C, Wood MJA, Gait MJ. “Peptide-mediated cell and in vivo delivery of antisense oligonucleotides and siRNA”. Mol Ther Nucleic Acids 1 (2012).
Tan S, Wu T, Zhang D, Zhang Z. “Cell or cell membrane-based drug delivery systems”. Theranostics 5 (2015): 863-881.
Piao L, Zhang M, Datta J, Xie X, Su T, et al. “Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma”. Mol Ther 20 (2012): 1261-1269.
Barba AA, Bochicchio S, Dalmoro A, Lamberti G. “Lipid delivery systems for nucleic-acid-based-drugs: from production to clinical applications”. Pharmaceutics 11 (2019): 360.
Multi-center, open label, extension study of ALN-VSP02 in cancer patients who have responded to ALN-VSP02 treatment (ClinicalTrials.gov Identifier: NCT01158079).
Aleku M, Schulz P, Keil O, Santel A, Schaeper U, et al. “Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression”. Cancer Res 68 (2008): 9788-98.
Northfelt DW, Hamburg SI, Borad MJ, Seetharam M, Curtis KK, et al. “A phase I dose-escalation study of TKM-080301, a RNAi therapeutic directed against polo-like kinase 1 (PLK1), in patients with advanced solid tumors: Expansion cohort evaluation of biopsy samples for evidence of pharmacodynamic effects of PLK1 inhibition”. Journal of Clinical Oncology 31 (2013): TPS2621-TPS2621.
El Dika I, Lim HY, Yong WP, Lin CC, Yoon JH, et al. “An openlabel, multicenter, phase i, dose escalation study with phase ii expansion cohort to determine the safety, pharmacokinetics, and preliminary antitumor activity of intravenous TKM- 080301 in subjects with advanced hepatocellular carcinoma”. Oncologist 24(2019): 747-e218.
Golan T, Khvalevsky EZ, Hubert A, Gabai RM, Hen N, et al. “RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients”. Oncotarget 6 (2015): 24560-24570.
Mainini F, Eccles MR. “Lipid and polymer-based nanoparticle siRNA delivery systems for cancer therapy”. Molecules (Basel, Switzerland) 25 (2020): 2692.
Yonezawa S, Koide H, Asai T. “Recent advances in siRNA delivery mediated by lipid-based nanoparticles:. Advanced drug delivery reviews (2020): S0169-409X(20)30106-X.
Kaczmarek JC, Kowalski PS, Anderson DG. “Advances in the delivery of RNA therapeutics: from concept to clinical reality”. Genome Med 9 (2017): 60.
Yuan X, Naguib S, Wu Z. “Recent advances of siRNA delivery by nanoparticles”. Expert Opinion Drug Delivery 8 (2011): 521-536.
Kulkarni JA, Cullis PR, van der Meel R. “Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility”. Nucleic Acid Therapeutics 28 (2018): 146-157.
