ABSTRACT BACKGROUND Mammary carcinogenesis possesses great challenges due to the lack of effectiveness of the multiple therapeutic options available. Gene therapy-based cancer treatment

strategy provides more targeting accuracy, fewer side effects, and higher therapeutic efficiency. Downregulation of the oncogene mTOR by mTOR-siRNA is an encouraging approach to reduce

cancer progression. However, its employment as means of therapeutic strategy has been restricted due to the unavailability of a suitable delivery system. METHODS A suitable nanocarrier

system made up of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) has been developed to prevent degradation and for proficient delivery of siRNA. This was followed by in vitro and in

DMBA-induced breast cancer. In addition, neutral liposome enhanced accumulation of siRNA in mammary cancer tissues facilitating its deep cytosolic distribution within the tumour, which

allows apoptosis thereby facilitating its anti-tumour potential. CONCLUSION Hence, the current study highlighted the augmented ground for therapies aiming toward cancerous cells to diminish

mTOR expression by RNAi in managing mammary carcinoma. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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METASTASIS Article 29 November 2021 REFERENCES * Zhou B, Li M, Xu X, Yang L, Ye M, Chen Y, et al. Integrin α2β1 targeting DGEA-modified liposomal doxorubicin enhances antitumor efficacy

against breast cancer. Mol Pharm. 2021;18:2634–46. Article  CAS  PubMed  Google Scholar  * Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. Article 

PubMed  Google Scholar  * Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al. Cancer statistics, 2020: report from National Cancer Registry Programme, India.

JCO Glob Oncol. 2020;6:1063–75. Article  PubMed  Google Scholar  * Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised

trials. Lancet. 1998;352:930–42. Article  Google Scholar  * Gentzler RD, Altman JK, Platanias LC. An overview of the mTOR pathway as a target in cancer therapy. Expert Opin Ther Targets.

2012;16:481–9. Article  CAS  PubMed  Google Scholar  * Sahu R, Pattanayak SP. Strategic developments & future perspective on gene therapy for breast cancer: role of mTOR and Brk/PTK6 as

molecular targets. Curr Gene Ther. 2020;20:237–58. Article  CAS  PubMed  Google Scholar  * Zou Z, Tao T, Li H, Zhu X. mTOR signaling pathway and mTOR inhibitors in cancer: progress and

challenges. Cell Biosci. 2020;10:1–1. Article  CAS  Google Scholar  * Tapia O, Riquelme I, Leal P, Sandoval A, Aedo S, Weber H, et al. The PI3K/AKT/mTOR pathway is activated in gastric

cancer with potential prognostic and predictive significance. Virchows Arch. 2014;465:25–33. Article  CAS  PubMed  Google Scholar  * Singh BN, Kumar D, Shankar S, Srivastava RK. Rottlerin

induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharm. 2012;84:1154–63. Article  CAS  PubMed

  Google Scholar  * Liu J, Li HQ, Zhou FX, Yu JW, Sun L, Han ZH. Targeting the mTOR pathway in breast cancer. Tumor Biol. 2017;39:1010428317710825. Article  Google Scholar  * Guerrero-Zotano

A, Mayer IA, Arteaga CL. PI3K/AKT/mTOR: role in breast cancer progression, drug resistance, and treatment. Cancer Metastasis Rev. 2016;35:515–24. Article  CAS  PubMed  Google Scholar  *

Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494–8. Article  CAS 

PubMed  Google Scholar  * Kapoor M, Burgess DJ, Patil SD. Physicochemical characterization techniques for lipid based delivery systems for siRNA. Int J Pharm. 2012;427:35–57. Article  CAS 

PubMed  Google Scholar  * Shen J, Zhang W, Qi R, Mao ZW, Shen H. Engineering functional inorganic–organic hybrid systems: advances in siRNA therapeutics. Chem Soc Rev. 2018;47:1969–95.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK. RNA interference in the clinic: challenges and future directions. Nat Rev

Cancer. 2011;11:59–67. Article  CAS  PubMed  Google Scholar  * Petros RA, DeSimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov.

2010;9:615–27. Article  CAS  PubMed  Google Scholar  * Chakrabarti S, Finnes HD, Mahipal A. Fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma: current status, insight

on resistance mechanisms and toxicity management. Expert Opin Drug Metab Toxicol. 2022;14:1–4. Google Scholar  * Rossi JJ, Rossi DJ. siRNA drugs: here to stay. Mol Ther. 2021;29:431–2.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov. 2009;8:129–38. Article 

CAS  PubMed  PubMed Central  Google Scholar  * Merritt WM, Bar-Eli M, Sood AK. The dicey role of Dicer: implications for RNAi therapy. Cancer Res. 2010;70:2571–4. Article  CAS  PubMed 

PubMed Central  Google Scholar  * Tanaka T, Mangala LS, Vivas-Mejia PE, Nieves-Alicea R, Mann AP, Mora E, et al. Sustained small interfering RNA delivery by mesoporous silicon particles.

Cancer Res. 2010;70:3687–96. Article  CAS  PubMed  PubMed Central  Google Scholar  * Di Paolo D, Brignole C, Pastorino F, Carosio R, Zorzoli A, Rossi M, et al. Neuroblastoma-targeted

nanoparticles entrapping siRNA specifically knockdown ALK. Mol Ther. 2011;19:1131–40. Article  PubMed  PubMed Central  Google Scholar  * Liyanage PY, Hettiarachchi SD, Zhou Y, Ouhtit A,

Seven ES, Oztan CY, et al. Nanoparticle-mediated targeted drug delivery for breast cancer treatment. Biochim Biophys Acta Rev Cancer. 2019;1871:419–33. Article  CAS  PubMed  PubMed Central 

Google Scholar  * Filion MC, Phillips NC. Major limitations in the use of cationic liposomes for DNA delivery. Int J Pharm. 1998;162:159–70. Article  CAS  Google Scholar  * Foged C, Nielsen

HM, Frokjaer S. Liposomes for phospholipase A2 triggered siRNA release: preparation and in vitro test. Int J Pharm. 2007;331:160–6. Article  CAS  PubMed  Google Scholar  * Halder J, Kamat

AA, Landen CN, Han LY, Lutgendorf SK, Lin YG, et al. Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin

Cancer Res. 2006;12:4916–24. Article  CAS  PubMed  PubMed Central  Google Scholar  * Landen CN, Chavez-Reyes A, Bucana C, Schmandt R, Deavers MT, Lopez-Berestein G, et al. Therapeutic EphA2

gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 2005;65:6910–8. Article  CAS  PubMed  Google Scholar  * Song Y, Zhou B, Du X, Wang Y, Zhang J, Ai

Y, et al. Folic acid (FA)-conjugated mesoporous silica nanoparticles combined with MRP-1 siRNA improves the suppressive effects of myricetin on non-small cell lung cancer (NSCLC). Biomed

Pharmacother. 2020;125:109561. Article  CAS  PubMed  Google Scholar  * Alinejad V, Somi MH, Baradaran B, Akbarzadeh P, Atyabi F, Kazerooni H, et al. Co-delivery of IL17RB siRNA and

doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells. Biomed Pharmacother. 2016;83:229–40. Article  CAS  PubMed  Google Scholar  * Kumar K,

Maiti B, Kondaiah P, Bhattacharya S. Efficacious gene silencing in serum and significant apoptotic activity induction by survivin downregulation mediated by new cationic gemini tocopheryl

lipids. Mol Pharm. 2015;12:351–61. Article  CAS  PubMed  Google Scholar  * Bose P, Priyam A, Kar R, Pattanayak SP. Quercetin loaded folate targeted plasmonic silver nanoparticles for light

activated chemo-photothermal therapy of DMBA induced breast cancer in Sprague Dawley rats. RSC Adv. 2020;10:31961–78(a). Article  CAS  PubMed  PubMed Central  Google Scholar  * Tekedereli I,

Alpay SN, Akar U, Yuca E, Ayugo-Rodriguez C, Han HD, et al. Therapeutic silencing of Bcl-2 by systemically administered siRNA nanotherapeutics inhibits tumor growth by autophagy and

apoptosis and enhances the efficacy of chemotherapy in orthotopic xenograft models of ER (−) and ER (+) breast cancer. Mol Ther Nucleic Acids. 2013;2:e121. Article  PubMed  PubMed Central 

Google Scholar  * Jin Y, Liang X, An Y, Dai Z. Microwave-triggered smart drug release from liposomes co-encapsulating doxorubicin and salt for local combined hyperthermia and chemotherapy of

cancer. Bioconjug Chem. 2016;27:2931–42. Article  CAS  PubMed  Google Scholar  * Tekedereli I, Alpay SN, Tavares CD, Cobanoglu ZE, Kaoud TS, Sahin I, et al. Targeted silencing of elongation

factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer. PLoS ONE. 2012;7:e41171. Article  CAS  PubMed  PubMed Central  Google Scholar

  * Li Y, Cheng Q, Jiang Q, Huang Y, Liu H, Zhao Y, et al. Enhanced endosomal/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA. J

Control Release. 2014;176:104–14. Article  CAS  PubMed  Google Scholar  * Acharya R, Chacko S, Bose P, Lapenna A, Pattanayak SP. Structure based multitargeted molecular docking analysis of

selected furanocoumarins against breast cancer. Sci Rep. 2019;9:1–3. Article  Google Scholar  * Haque MW, Bose P, Siddique MU, Sunita P, Lapenna A, Pattanayak SP. Taxifolin binds with LXR (α

& β) to attenuate DMBA-induced mammary carcinogenesis through mTOR/Maf-1/PTEN pathway. Biomed Pharmacother. 2018;105:27–36. Article  CAS  PubMed  Google Scholar  * Kumar A, Sunita P,

Jha S, Pattanayak SP. Daphnetin inhibits TNF‐α and VEGF‐induced angiogenesis through inhibition of the IKK s/IκBα/NF‐κB, Src/FAK/ERK 1/2 and Akt signalling pathways. Clin Exp Pharm Physiol.

2016;43:939–50. Article  CAS  Google Scholar  * Xiao W, Zhang W, Huang H, Xie Y, Zhang Y, Guo X, et al. Cancer targeted gene therapy for inhibition of melanoma lung metastasis with eiF3i

shRNA loaded liposomes. Mol Pharm. 2019;17:229–38. Article  PubMed  Google Scholar  * Bertrand JR, Pottier M, Vekris A, Opolon P, Maksimenko A, Malvy C. Comparison of antisense

oligonucleotides and siRNAs in cell culture and in vivo. Biochem Biophys Res Commun. 2002;296:1000–4. Article  CAS  PubMed  Google Scholar  * Sahu R, Kar RK, Sunita P, Bose P, Kumari P,

Bharti S, et al. LC-MS characterized methanolic extract of Zanthoxylum armatum possess anti-breast cancer activity through nrf2-keap1 pathway: an in-silico, in-vitro and in-vivo evaluation.

J Ethnopharmacol. 2021;269:113758. Article  CAS  PubMed  Google Scholar  * Kumar A, Sunita P, Jha S, Pattanayak SP. 7, 8-Dihydroxycoumarin exerts antitumor potential on DMBA-induced mammary

carcinogenesis by inhibiting ERα, PR, EGFR, and IGF1R: involvement of MAPK1/2-JNK1/2-Akt pathway. J Physiol Biochem. 2018;74:223–34. Article  CAS  PubMed  Google Scholar  * Chen Y, Zhu X,

Zhang X, Liu B, Huang L. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther. 2010;18:1650–6. Article  CAS  PubMed  PubMed Central  Google

Scholar  * Clogston JD, Patri AK. Zeta potential measurement. Methods Mol Biol. 2011;697:63–70. Article  CAS  PubMed  Google Scholar  * Plumb JA. Cell sensitivity assays: clonogenic assay.

In: Langdon SP, editor. Cancer cell culture, methods in molecular medicine. Totowa, NJ: Humana Press Inc.; 2004. pp. 159–64. * Teymouri M, Badiee A, Golmohammadzadeh S, Sadri K, Akhtari J,

Mellat M, et al. Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: an in vitro and in vivo study on drug cellular delivery, release, biodistribution

and antitumor activity. Int J Pharm. 2016;511:236–44. Article  CAS  PubMed  Google Scholar  * Barenholz YC. Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release.

2012;160:117–34. Article  CAS  PubMed  Google Scholar  * Walkey CD, Olsen JB, Guo H, Emili A, Chan WC. Nanoparticle size and surface chemistry determine serum protein adsorption and

macrophage uptake. J Am Chem Soc. 2012;134:2139–47. Article  CAS  PubMed  Google Scholar  * Argilés JM, Azcón-Bieto J. The metabolic environment of cancer. Mol Cell Biochem. 1988;81:3–17.

Article  PubMed  Google Scholar  * Pattanayak SP, Mazumder PM. Therapeutic potential of Dendrophthoe falcata (Lf) Ettingsh on 7, 12-dimethylbenz (a) anthracene-induced mammary tumorigenesis

in female rats: effect on antioxidant system, lipid peroxidation, and hepatic marker enzymes. Comp Clin Pathol. 2011;20:381–92. Article  Google Scholar  * Song F, Sakurai N, Okamoto A, Koide

H, Oku N, Dewa T, et al. Design of a novel PEGylated liposomal vector for systemic delivery of siRNA to solid tumors. Biol Pharm Bull. 2019;42:996–1003. Article  CAS  PubMed  Google Scholar

  * Badran M, Shalaby K, Al-Omrani A. Influence of the flexible liposomes on the skin deposition of a hydrophilic model drug, carboxyfluorescein: dependency on their composition. Sci World J

2012;2012:134876. Article  Google Scholar  * Yang C, Attia AB, Tan JP, Ke X, Gao S, Hedrick JL, et al. The role of non-covalent interactions in anticancer drug loading and kinetic stability

of polymeric micelles. Biomaterials. 2012;33:2971–9. Article  CAS  PubMed  Google Scholar  * Desai MP, Labhasetwar V, Amidon GL, Levy RJ. Gastrointestinal uptake of biodegradable

microparticles: effect of particle size. Pharm Res. 1996;13:1838–45. Article  CAS  PubMed  Google Scholar  * Prakash S, Malhotra M, Shao W, Tomaro-Duchesneau C, Abbasi S. Polymeric

nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv Drug Deliv Rev. 2011;63:1340–51. Article  CAS  PubMed  Google Scholar  * Haley B, Frenkel E.

Nanoparticles for drug delivery in cancer treatment. Urol Oncol. 2008;26:57–64. Article  CAS  PubMed  Google Scholar  * Arranja AG, Pathak V, Lammers T, Shi Y. Tumor-targeted nanomedicines

for cancer theranostics. Pharm Res. 2017;115:87–95. Article  CAS  Google Scholar  * Miller CR, Bondurant B, McLean SD, McGovern KA, O’Brien DF. Liposome− cell interactions in vitro: effect

of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry 1998;37:12875–83. Article  CAS  PubMed  Google Scholar  * Lieleg

O, Baumgärtel RM, Bausch AR. Selective filtering of particles by the extracellular matrix: an electrostatic bandpass. Biophys J. 2009;97:1569–77. Article  CAS  PubMed  PubMed Central  Google

Scholar  * Nomura T, Koreeda N, Yamashita F, Takakura Y, Hashida M. Effect of particle size and charge on the disposition of lipid carriers after intratumoral injection into tissue-isolated

tumors. Pharm Res. 1998;15:128–32. Article  CAS  PubMed  Google Scholar  * Xia Y, Tian J, Chen X. Effect of surface properties on liposomal siRNA delivery. Biomaterials 2016;79:56–68.

Article  CAS  PubMed  Google Scholar  * Easton JB, Houghton PJ. mTOR and cancer therapy. Oncogene. 2006;25:6436–46. Article  CAS  PubMed  Google Scholar  * Hay N, Sonenberg N. Upstream and

downstream of mTOR. Genes Dev. 2004;18:1926–45. Article  CAS  PubMed  Google Scholar  * Vara JÁ, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling

pathway and cancer. Cancer Treat Rev. 2004;30:193–204. Article  CAS  Google Scholar  * Butt G, Shahwar D, Qureshi MZ, Attar R, Akram M, Birinci Y, et al. Role of mTORC1 and mTORC2 in breast

cancer: therapeutic targeting of mTOR and its partners to overcome metastasis and drug resistance. Adv Exp Med Biol. 2019;1152:283–92. * Ma BL, Shan MH, Sun G, Ren GH, Dong C, Yao X, et al.

Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer. Mol Med Rep. 2015;12:5246–54. Article  CAS 

PubMed  Google Scholar  * Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature.

2012;485:55–61. Article  CAS  PubMed  PubMed Central  Google Scholar  * Steeg PS. Targeting metastasis. Nat Rev Cancer. 2016;16:201–18. Article  CAS  PubMed  PubMed Central  Google Scholar 

* Berven LA, Willard FS, Crouch MF. Role of the p70S6K pathway in regulating the actin cytoskeleton and cell migration. Exp Cell Res. 2004;296:183–95. Article  CAS  PubMed  Google Scholar  *

Chen JS, Wang Q, Fu XH, Huang XH, Chen XL, Cao LQ, et al. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: association with MMP‐9. Hepatol

Res. 2009;39:177–86. Article  CAS  PubMed  Google Scholar  * Liu L, Li F, Cardelli JA, Martin KA, Blenis J, Huang S. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and

4E-BP1 pathways. Oncogene 2006;25:7029–40. Article  CAS  PubMed  Google Scholar  * Langer EM, Kendsersky ND, Daniel CJ, Kuziel GM, Pelz C, Murphy KM, et al. ZEB1-repressed microRNAs inhibit

autocrine signaling that promotes vascular mimicry of breast cancer cells. Oncogene 2018;37:1005–19. Article  CAS  PubMed  Google Scholar  * Verrax J, Defresne F, Lair F, Vandermeulen G,

Rath G, Dessy C, et al. Delivery of soluble VEGF receptor 1 (sFlt1) by gene electrotransfer as a new antiangiogenic cancer therapy. Mol Pharm. 2011;8:701–8. Article  CAS  PubMed  Google

Scholar  * Mollard S, Mousseau Y, Baaj Y, Richard L, Cook-Moreau J, Monteil J, et al. How can grafted breast cancer models be optimized? Cancer Biol Ther. 2011;12:855–64. Article  CAS 

PubMed  PubMed Central  Google Scholar  * Haque MW, Pattanayak SP. Taxifolin inhibits 7, 12-dimethylbenz (a) anthracene-induced breast carcinogenesis by regulating AhR/CYP1A1 signaling

pathway. Pharmacogn Mag. 2017;13:S749–55. Google Scholar  * Bose P, Pattanayak SP, Priyam A. Herniarin, a natural coumarin loaded novel targeted plasmonic silver nanoparticles for light

activated chemo-photothermal therapy in preclinical model of breast cancer. Pharmacogn Mag. 2020;16:474–85 (b). Article  Google Scholar  * Zhang HW, Hu JJ, Fu RQ, Liu X, Zhang YH, Li J, et

al. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells.

Sci Rep. 2018;8:1–3. Google Scholar  * Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J cancer. 1972;26:239–57.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Spagnou S, Miller AD, Keller M. Lipidic carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid

DNA. Biochemistry. 2004;43:13348–56. Article  CAS  PubMed  Google Scholar  * Wagner MJ, Mitra R, McArthur MJ, Baze W, Barnhart K, Wu SY, et al. Preclinical mammalian safety studies of

EPHARNA (DOPC nanoliposomal EphA2-targeted siRNA). Mol Cancer Ther. 2017;16:1114–23. Article  CAS  PubMed  PubMed Central  Google Scholar  * Sonoke S, Ueda T, Fujiwara K, Sato Y, Takagaki K,

Hirabayashi K, et al. Tumor regression in mice by delivery of Bcl-2 small interfering RNA with pegylated cationic liposomes. Cancer Res. 2008;68:8843–51. Article  CAS  PubMed  Google

Scholar  Download references ACKNOWLEDGEMENTS We acknowledge the support provided by the Central Instrumentation facility (CIF), Birla Institute of Technology, Mesra, Ranchi and HR-TEM

facility of Vellore Institute of Technology in the characterisation of liposomal preparation. FUNDING This study was supported by Department of Pharmaceutical Sciences and Technology, Birla

Institute of Technology, Mesra, Ranchi, India. This work has been funded by UGC (201819-NFO-2018-19-OBC-ORI-80495). AUTHOR INFORMATION Author notes * These authors contributed equally: Roja

Sahu, Shakti Prasad Pattanayak. AUTHORS AND AFFILIATIONS * Division of Advanced Pharmacology, Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology (BIT),

Mesra, Ranchi, Jharkhand, 835 215, India Roja Sahu * Division of Pharmacognosy and Phytochemistry, Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology

(BIT), Mesra, Ranchi, Jharkhand, 835 215, India Shivesh Jha * Department of Pharmacy, School of Health Science, Central University of South Bihar (Gaya), Gaya, Bihar, 824 236, India Shakti

Prasad Pattanayak Authors * Roja Sahu View author publications You can also search for this author inPubMed Google Scholar * Shivesh Jha View author publications You can also search for this

author inPubMed Google Scholar * Shakti Prasad Pattanayak View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS RS and SPP conducted the

experiments and wrote the manuscript with equal contribution. SPP and RS was responsible for confocal microscopy, Western blot, immunohistochemistry and flow cytometry. RS and SJ took part

in the in vivo experiments. SJ analysed the data and revised the manuscript. SPP designed the research plan, analysed the data and revised the manuscript. All authors have approved the

manuscript. CORRESPONDING AUTHOR Correspondence to Shakti Prasad Pattanayak. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICS APPROVAL AND CONSENT

TO PARTICIPATE This animal study was approved by the Institutional Animal Ethical Committee, Birla Institute of Technology, Mesra, Ranchi (approval no. 1972/PH/BIT/113/20/IAEC). All animal

experiments were conducted in accordance with the Institutional Animal Ethical Committee (IAEC) regulation. This study did not include patient participation or analysis of patient data.

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such publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sahu, R., Jha, S. & Pattanayak, S.P. Therapeutic silencing of mTOR by

systemically administered siRNA-loaded neutral liposomal nanoparticles inhibits DMBA-induced mammary carcinogenesis. _Br J Cancer_ 127, 2207–2219 (2022).

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