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Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery

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Abstract

Patients with glioblastoma multiforme and anaplastic astrocytoma are treated with temozolomide. Although it has been demonstrated that temozolomide increases GBM patient survival, it has also been connected to negative immune-related adverse effects. Numerous research investigations have shown that flavonoids have strong antioxidant and chemo-preventive effects. Consequently, it might lessen chemotherapeutic medicines’ side effects while also increasing therapeutic effectiveness. The need for creating innovative, secure, and efficient drug carriers for cancer therapy has increased over time. Recent research indicates that exosomes have enormous potential to serve as carriers and cutting-edge drug delivery systems to the target cell. In recent years, researchers have been paying considerable attention to exosomes because of their favorable biodistribution, biocompatibility, and low immunogenicity. In the present review, the mechanistic information of the anti-glioblastoma effects of temozolomide and flavonoids coupled with their exosomal delivery to the targeted cell has been discussed. In addition, we discuss the safety aspects of temozolomide and flavonoids against glioma. The in-depth information of temozolomide and flavonoids action via exosomal delivery can unravel novel strategies to target Glioma.

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References

  • Agarwala SS, Kirkwood JM (2000) Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Oncologist 5:144–151

    Article  PubMed  CAS  Google Scholar 

  • Aggarwal V, Tuli HS, Kaur J, Aggarwal D, Parashar G, Chaturvedi Parashar N, Kulkarni S, Kaur G, Sak K, Kumar M (2020) Garcinol exhibits anti-neoplastic effects by targeting diverse oncogenic factors in tumor cells. Biomedicines 8:103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Aili Y, Maimaitiming N, Mahemuti Y, Qin H, Wang Y, Wang Z (2021) The role of exosomal miRNAs in glioma: biological function and clinical application. Front Oncol 11:686369

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Akhlaghi M, Foshati S (2017) Bioavailability and metabolism of flavonoids: a review. Int J Nutri Sci 2:180–184

    CAS  Google Scholar 

  • Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  PubMed  CAS  Google Scholar 

  • Aqil F, Kausar H, Agrawal AK, Jeyabalan J, Kyakulaga A-H, Munagala R, Gupta R (2016) Exosomal formulation enhances therapeutic response of celastrol against lung cancer. Exp Mol Pathol 101:12–21

    Article  PubMed  CAS  Google Scholar 

  • Aqil F, Jeyabalan J, Agrawal AK, Kyakulaga A-H, Munagala R, Parker L, Gupta RC (2017) Exosomal delivery of berry anthocyanidins for the management of ovarian cancer. Food Funct 8:4100–4107

    Article  PubMed  CAS  Google Scholar 

  • Arora A, Somasundaram K (2019) Glioblastoma vs temozolomide: can the red queen race be won? Cancer Biol Ther 20:1083–1090

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Atiq A, Parhar I (2020) Anti-neoplastic potential of flavonoids and polysaccharide phytochemicals in glioblastoma. Molecules 25:4895

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bai ZL, Tay V, Guo SZ, Ren J, Shu MG (2018) Silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mTOR and YAP. BioMed Res Int 2018:1–10

    Google Scholar 

  • Bai L, Liu Y, Guo K, Zhang K, Liu Q, Wang P, Wang X (2019) Ultrasound facilitates naturally equipped exosomes derived from macrophages and blood serum for orthotopic glioma treatment. ACS Appl Mater Interfaces 11:14576–14587

    Article  PubMed  CAS  Google Scholar 

  • Bang C, Thum T (2012) Exosomes: new players in cell–cell communication. Int J Biochem Cell Biol 44:2060–2064

    Article  PubMed  CAS  Google Scholar 

  • Beylerli O, Beilerli A, Shumadalova A, Wang X, Yang M, Sun H, Teng L (2022) Therapeutic effect of natural polyphenols against glioblastoma. Front Cell Dev Biol 10:1036809

  • Brada M, Judson I, Beale P, Moore S, Reidenberg P, Statkevich P, Dugan M, Batra V, Cutler D (1999) Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br J Cancer 81:1022–1030

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brandes A, Ermani M, Basso U, Amista P, Berti F, Scienza R, Rotilio A, Pinna G, Gardiman M, Monfardini S (2001) Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study. Ann Oncol 12:255–258

    Article  PubMed  CAS  Google Scholar 

  • Carobolante G, Mantaj J, Ferrari E, Vllasaliu D (2020) Cow milk and intestinal epithelial cell-derived extracellular vesicles as systems for enhancing oral drug delivery. Pharmaceutics 12:226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cassidy A, Minihane A-M (2017) The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am J Clin Nutr 105:10–22

    Article  PubMed  CAS  Google Scholar 

  • Chang JE, Khuntia D, Robins HI, Mehta MP (2007) Radiotherapy and radiosensitizers in the treatment of glioblastoma multiforme. Clin Adv Hematol Oncol 5:894–902

    PubMed  Google Scholar 

  • Chen YY, Chang YM, Wang KY, Chen PN, Hseu YC, Chen KM, Yeh KT, Chen CJ, Hsu LS (2019) Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms. Environ Toxicol 34:233–239

    Article  PubMed  CAS  Google Scholar 

  • Chen B, Li X, Wu L, Zhou D, Song Y, Zhang L, Wu Q, He Q, Wang G, Liu X (2022a) Quercetin suppresses human glioblastoma migration and invasion via GSK3β/β-catenin/ZEB1 signaling pathway. Front Pharmacol 13:4678

    Google Scholar 

  • Chen M, Zhao H, Cheng Y, Wang L, Alotaibi SH, Zhang Y (2022b) Anti-human glioma cancer potentials of neobavaisoflavone as natural antioxidant compound and its inhibition profiles for acetylcholinesterase and butyrylcholinesterase enzymes with molecular modeling and spin density distributions studies. J Oleo Sci 71:277–288

    Article  PubMed  CAS  Google Scholar 

  • Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM, Cheng HH, Arroyo JD, Meredith EK, Gallichotte EN (2014) Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci 111:14888–14893

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Choi JU, Park IK, Lee YK, Hwang SR (2020) The biological function and therapeutic potential of exosomes in cancer: exosomes as efficient nanocommunicators for cancer therapy. Int J Mol Sci 21:7363

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cui J, Wang X, Li J, Zhu A, Du Y, Zeng W, Guo Y, Di L, Wang R (2023) Immune exosomes loading self-assembled nanomicelles traverse the blood–brain barrier for chemo-immunotherapy against glioblastoma. ACS Nano 17:1464–1484

    Article  CAS  Google Scholar 

  • Das A, Banik NL, Ray SK (2010) Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes. Cancer: Interdiscip Int J Am Cancer Soc 116:164–176

    Article  CAS  Google Scholar 

  • Davis ME (2016) Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs 20:S2

    Article  PubMed  PubMed Central  Google Scholar 

  • Deep G, Agarwal R (2010) Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev 29:447–463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Denny BJ, Wheelhouse RT, Stevens MF, Tsang LL, Slack JA (1994) NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry 33:9045–9051

    Article  PubMed  CAS  Google Scholar 

  • Donoso-Quezada J, Guajardo-Flores D, González-Valdez J (2020) Enhanced exosome-mediated delivery of black bean phytochemicals (Phaseolus vulgaris L.) for cancer treatment applications. Biomed Pharm 131:110771

    Article  CAS  Google Scholar 

  • Estlin E, Lashford L, Ablett S, Price L, Gowing R, Gholkar A, Kohler J, Lewis I, Morland B, Pinkerton C (1998) Phase I study of temozolomide in paediatric patients with advanced cancer. Br J Cancer 78:652–661

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fan B, Yang S, Wang Y-Y, Zhang C, Yang JP, Wang LQ, Lv ZQ, Shi XF, Fan ZZ, Yang JK (2022) Indocyanine green-loaded exosomes for image-guided glioma nano-therapy. J Exp Nanosci 17:187–196

    Article  CAS  Google Scholar 

  • Friedman HS, Kerby T, Calvert H (2000) Temozolomide and treatment of malignant glioma. Clin Cancer Res 6:2585–2597

    PubMed  CAS  Google Scholar 

  • Galati G, O’brien PJ (2004) Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Rad Biol Med 37:287–303

    Article  PubMed  CAS  Google Scholar 

  • Gurunathan S, Kang M, Jeyaraj M, Qasim M, Kim J (2019) Review of the Isolation Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes. Cells 8:307

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gurung S, Perocheau D, Touramanidou L, Baruteau J (2021) The exosome journey: From biogenesis to uptake and intracellular signalling. Cell Commun Signal 19:1–19

    Article  Google Scholar 

  • Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • He Y, Kaina B (2019) Are there thresholds in glioblastoma cell death responses triggered by temozolomide? Int J Mol Sci 20:1562

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hood JL (2016) Post isolation modification of exosomes for nanomedicine applications. Nanomedicine 11:1745–1756

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hosseini MM, Karimi A, Behroozaghdam M, Javidi MA, Ghiasvand S, Bereimipour A, Aryan H, Nassiri F, Jangholi E (2017) Cytotoxic and apoptogenic effects of cyanidin-3-glucoside on the glioblastoma cell line. World Neurosurgery 108:94–100

    Article  PubMed  Google Scholar 

  • Huang S, Xue P, Han X, Zhang C, Yang L, Liu L, Wang X, Li H, Fu J, Zhou Y (2020) Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis. Cell Death Dis 11:408

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iacob G, Dinca EB (2009) Current data and strategy in glioblastoma multiforme. J Med Life 2:386

    PubMed  PubMed Central  Google Scholar 

  • Jia G, Han Y, An Y, Ding Y, He C, Wang X, Tang Q (2018) NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials 178:302–316

    Article  PubMed  CAS  Google Scholar 

  • Jia S, Xu X, Zhou S, Chen Y, Ding G, Cao L (2019) Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress-and mitochondrial stress-dependent pathways. Cell Death Dis 10:142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jiapaer S, Furuta T, Tanaka S, Kitabayashi T, Nakada M (2018) Potential strategies overcoming the temozolomide resistance for glioblastoma. Neurol Med Chir 58:405

    Article  Google Scholar 

  • Joshi H, Kumar G, Tuli HS, Mittal S (2023) Inhibition of cancer cell metastasis by nanotherapeutics: current achievements and future trends. In: Nanotherapeutics in cancer, Jenny Stanford Publishing, pp 161–209

  • Kabala-Dzik A, Rzepecka-Stojko A, Kubina R, Iriti M, Wojtyczka RD, Buszman E, Stojko J (2018) Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7: A comparative study. Cell Mol Biol 64:1–10

    Article  PubMed  Google Scholar 

  • Kalani A, Kamat P, Chaturvedi P, Tyagi S, Tyagi N (2014) Curcumin-primed exosomes mitigate endothelial cell dysfunction during hyperhomocysteinemia. Life Sci 107:1–7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kalluri R, LeBleu VS (2020) The biology, function, and biomedical applications of exosomes. Science 367:6977

    Article  Google Scholar 

  • Katakowski M, Buller B, Zheng X, Lu Y, Rogers T, Osobamiro O, Shu W, Jiang F, Chopp M (2013) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335:201–204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawser Hossain M, AbdalDayem A, Han J, Yin Y, Kim K, Kumar Saha S, Yang GM, Choi HY, Cho SG (2016) Molecular mechanisms of the anti-obesity and anti-diabetic properties of flavonoids. Int J Mol Sci 17:569

    Article  PubMed  PubMed Central  Google Scholar 

  • Kelly G (2011) Quercetin Monograph (in Eng). Altern Med Rev 16:1–72

    Google Scholar 

  • Kesari S (2011) Understanding glioblastoma tumor biology: the potential to improve current diagnosis and treatments. Proc Semin oncol 38:2–10

    Article  Google Scholar 

  • Khan H, Ullah H, Martorell M, Valdes SE, Belwal T, Tejada S, Sureda A, Kamal MA (2021) Flavonoids nanoparticles in cancer: treatment, prevention and clinical prospects. Proc Semin Cancer Biol 69:200–211

    Article  CAS  Google Scholar 

  • Khatami SH, Karami N, Taheri-Anganeh M, Taghvimi S, Tondro G, Khorsand M, SoltaniFard E, Sedighimehr N, Kazemi M, RahimiJaberi K (2023) Exosomes: promising delivery tools for overcoming blood-brain barrier and glioblastoma therapy. Mol Neurobiol 60(8):4659–4678

    Article  PubMed  CAS  Google Scholar 

  • Khaw AK, Yong JWY, Kalthur G, Hande MP (2012) Genistein induces growth arrest and suppresses telomerase activity in brain tumor cells. Genes Chromosom Cancer 51:961–974

    Article  PubMed  CAS  Google Scholar 

  • Kim G, Kim M, Lee Y, Byun JW, Lee M (2020) Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. J Control Release 317:273–281

    Article  PubMed  CAS  Google Scholar 

  • Koklesova L, Liskova A, Samec M, Zhai K, Abotaleb M, Ashrafizadeh M, Brockmueller A, Shakibaei M, Biringer K, Bugos O (2020) Carotenoids in cancer metastasis—status quo and outlook. Biomolecules 10:1653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ, Weichselbaum RR, McCarthy BJ (2012) Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol 107:207–212

    Article  PubMed  Google Scholar 

  • Koukourakis GV, Kouloulias V, Zacharias G, Papadimitriou C, Pantelakos P, Maravelis G, Fotineas A, Beli I, Chaldeopoulos D, Kouvaris J (2009) Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article. Molecules 14:1561–1577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lamy S, Lafleur R, Bédard V, Moghrabi A, Barrette S, Gingras D, Béliveau R (2007) Anthocyanidins inhibit migration of glioblastoma cells: structure-activity relationship and involvement of the plasminolytic system. J Cell Biochem 100:100–111

    Article  PubMed  CAS  Google Scholar 

  • Le CT, Leenders WP, Molenaar RJ, van Noorden CJ (2018) Effects of the green tea polyphenol epigallocatechin-3-gallate on glioma: a critical evaluation of the literature. Nutr Cancer 70:317–333

    Article  PubMed  CAS  Google Scholar 

  • Lee SY (2016) Temozolomide resistance in glioblastoma multiforme. Gen Dis 3:198–210

    Google Scholar 

  • Lee H-S, Park B-S, Kang H-M, Kim J-H, Shin S-H, Kim I-R (2021) Role of luteolin-induced apoptosis and autophagy in human glioblastoma cell lines. Medicina 57:879

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee H, Bae K, Baek A-R, Kwon E-B, Kim Y-H, Nam S-W, Lee GH, Chang Y (2022) Glioblastoma-derived exosomes as nanopharmaceutics for improved glioma treatment. Pharmaceutics 14:1002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li S-P, Lin Z-X, Jiang X-Y, Yu X-Y (2018) Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacol Sin 39:542–551

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li X, Guan J, Jiang Z, Cheng S, Hou W, Yao J, Wang Z (2021) Microglial exosome miR-7239-3p promotes glioma progression by regulating circadian genes. Neurosci Bull 37:497–510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Y, Meng L, Li B, Li Y, Shen T, Zhao B (2022) The exosome journey: from biogenesis to regulation and function in cancers. J Oncol 2022:1–13

    Google Scholar 

  • Li B, Chen X, Qiu W, Zhao R, Duan J, Zhang S, Pan Z, Zhao S, Guo Q, Qi Y (2022b) Synchronous disintegration of ferroptosis defense axis via engineered exosome-conjugated magnetic nanoparticles for glioblastoma therapy. Adv Sci 9:2105451

    Article  CAS  Google Scholar 

  • Liskova A, Samec M, Koklesova L, Brockmueller A, Zhai K, Abdellatif B, Siddiqui M, Biringer K, Kudela E, Pec M (2021) Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles. EPMA Journal 12:155–176

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Tang Z-G, Yang J-Q, Zhou Y, Meng L-H, Wang H, Li C-L (2017) Low concentration of quercetin antagonizes the invasion and angiogenesis of human glioblastoma U251 cells. Onco Targets Ther 10:4023

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu X, Wang Q, Liu B, Zheng X, Li P, Zhao T, Jin X, Ye F, Zhang P, Chen W (2021) Genistein inhibits radiation-induced invasion and migration of glioblastoma cells by blocking the DNA-PKcs/Akt2/Rac1 signaling pathway. Radiother Oncol 155:93–104

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Xia T, Fang Y, Zuo H, Dong X, Xu P, Ouyang J (2022) Overcoming the blood–brain barrier by using a multistage exosome delivery system to inhibit central nervous system lymphoma. Nanomedicine Nanotechnol, Biol Med 41:102523

    Article  CAS  Google Scholar 

  • Liu W, Wei L, Li M, Mo J (2023) Zinc sulfide-based hybrid exosome-coated nanoplatform for targeted treatment of glioblastoma in an orthotopic mouse glioblastoma model. Mater Today Adv 17:100327

    Article  CAS  Google Scholar 

  • Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D (2017) Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin 38:754–763

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Makowska M, Smolarz B, Romanowicz H (2023) microRNAs (miRNAs) in glioblastoma multiforme (GBM)—recent literature review. Int J Mol Sci 24:3521

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Manach C, Williamson G, Morand C, Scalbert A, Rémésy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutri 1:230-242S

    Article  Google Scholar 

  • Messaoudi K, Clavreul A, Lagarce F (2015) Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Dis Today 20:899–905

    Article  CAS  Google Scholar 

  • Minciacchi VR, Freeman MR, Di Vizio D (2015) Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes, vol 40. In: Seminars in cell & developmental biology, pp 41–51

  • Mrugala MM (2013) Advances and challenges in the treatment of glioblastoma: a clinician’s perspective. Discov Med 15:221–230

    PubMed  Google Scholar 

  • Munagala R, Aqil F, Jeyabalan J, Agrawal AK, Mudd AM, Kyakulaga AH, Singh IP, Vadhanam MV, Gupta RC (2017) Exosomal formulation of anthocyanidins against multiple cancer types. Cancer Lett 393:94–102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Noack A, Gericke B, von Köckritz-Blickwede M, Menze A, Noack S, Gerhauser I, Osten F, Naim HY, Löscher W (2018) Mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils. Proc Natl Acad Sci 115:E9590–E9599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nooshabadi VT, Khanmohammadi M, Shafei S, Banafshe HR, Malekshahi ZV, Ebrahimi-Barough S, Ai J (2020) Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model. Biochem Biophys Rep 23:100792

    PubMed  PubMed Central  Google Scholar 

  • Ohka F, Natsume A, Wakabayashi T (2012) Current trends in targeted therapies for glioblastoma multiforme. Neurol Res Int 2012:1–13

    Article  Google Scholar 

  • Pan H-C, Jiang Q, Yu Y, Mei J-P, Cui Y-K, Zhao W-J (2015) Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells. Neurochem Int 80:60–71

    Article  PubMed  CAS  Google Scholar 

  • Peng J, Liang Q, Xu Z, Cai Y, Peng B, Li J, Zhang W, Kang F, Hong Q, Yan Y (2022) Current understanding of exosomal microRNAs in glioma immune regulation and therapeutic responses. Front Immunol 12:813747

    Article  PubMed  PubMed Central  Google Scholar 

  • Petrenko D, Chubarev V, Syzrantsev N, Ismail N, Merkulov V, Sologova S, Grigorevskikh E, Smolyarchuk E, Alyautdin R (2022) Temozolomide efficacy and metabolism: the implicit relevance of nanoscale delivery systems. Molecules 27:3507

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pietrantonio F, Randon G, Romagnoli D, Di Donato S, Benelli M, de Braud F (2020) Biomarker-guided implementation of the old drug temozolomide as a novel treatment option for patients with metastatic colorectal cancer. Cancer Treat Rev 82:101935

    Article  PubMed  CAS  Google Scholar 

  • Portnow J, Badie B, Chen M, Liu A, Blanchard S, Synold TW (2009) The neuropharmacokinetics of temozolomide in patients with resectable brain tumors: potential implications for the current approach to chemoradiation Neuropharmacokinetics of temozolomide. Clin Cancer Res 15:7092–7098

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Quan R, Zhang H, Li Z, Li X (2020) Survival analysis of patients with glioblastoma treated by long-term administration of temozolomide. Medicine 99(2):18591

    Article  Google Scholar 

  • Reardon DA, Wen PY (2006) Therapeutic advances in the treatment of glioblastoma: rationale and potential role of targeted agents. Oncologist 11:152–164

    Article  PubMed  CAS  Google Scholar 

  • Record M (2014) Intercellular communication by exosomes in placenta: a possible role in cell fusion? Placenta 35:297–302

    Article  PubMed  CAS  Google Scholar 

  • Rehman FU, Liu Y, Yang Q, Yang H, Liu R, Zhang D, Muhammad P, Liu Y, Hanif S, Ismail M (2022) Heme oxygenase-1 targeting exosomes for temozolomide resistant glioblastoma synergistic therapy. J Control Release 345:696–708

    Article  PubMed  CAS  Google Scholar 

  • Reid JM, Stevens DC, Rubin J, Ames MM (1997) Pharmacokinetics of 3-methyl-(triazen-1-yl) imidazole-4-carboximide following administration of temozolomide to patients with advanced cancer. Clin Cancer Res: an Off J Am Assoc Cancer Res 3:2393–2398

    CAS  Google Scholar 

  • Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34

    Article  PubMed  CAS  Google Scholar 

  • Rubio-Camacho M, Encinar JA, Martínez-Tomé MJ, Esquembre R, Mateo CR (2020) The interaction of temozolomide with blood components suggests the potential use of human serum albumin as a biomimetic carrier for the drug. Biomolecules 10:1015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saari H, Lázaro-Ibáñez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M (2015) Microvesicle-and exosome-mediated drug delivery enhances the cytotoxicity of paclitaxel in autologous prostate cancer cells. J Control Release 220:727–737

    Article  PubMed  CAS  Google Scholar 

  • Samec M, Liskova A, Koklesova L, Mersakova S, Strnadel J, Kajo K, Pec M, Zhai K, Smejkal K, Mirzaei S (2021) Flavonoids targeting HIF-1: implications on cancer metabolism. Cancers 13:130

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Santos BL, Oliveira MN, Coelho PL, Pitanga BP, Da Silva AB, Adelita T, Silva VDA, de Costa FDM, El-Bacha RS, Tardy M (2015) Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression. Chem-Biol Interact 242:123–138

    Article  PubMed  CAS  Google Scholar 

  • Sargazi ML, Juybari KB, Tarzi ME, Amirkhosravi A, Nematollahi MH, Mirzamohammdi S, Mehrbani M, Mehrabani M, Mehrabani M (2021) Naringenin attenuates cell viability and migration of C6 glioblastoma cell line: a possible role of hedgehog signaling pathway. Mol Biol Rep 48:6413–6421

    Article  PubMed  CAS  Google Scholar 

  • Scott J, Tsai YY, Chinnaiyan P, Yu HHM (2011) Effectiveness of radiotherapy for elderly patients with glioblastoma. Int J Radia Oncol Biol Phys 1:206–210

    Article  Google Scholar 

  • Sharma S, Sharma U (2022) Exosomes in cardiovascular diseases: a blessing or a sin for the mankind. Mol Cell Biochem 477:833–847

    Article  PubMed  CAS  Google Scholar 

  • Sharma A, Ghani A, Sak K, Tuli HS, Sharma AK, Setzer WN, Sharma S, Das AK (2019a) Probing into therapeutic anti-cancer potential of apigenin: recent trends and future directions. Recent Pat Inflamm Allergy Drug Dis 13:124–133

    Article  CAS  Google Scholar 

  • Sharma C, Bhardwaj N, Sharma A, Tuli HS, Batra P, Beniwal V, Gupta GK, Sharma AK (2019b) Bioactive metabolites of Ganoderma lucidum: factors, mechanism and broad spectrum therapeutic potential. Journal of Herbal Medicine 17:100268

    Article  Google Scholar 

  • Sheikh I, Sharma V, Tuli HS, Aggarwal D, Sankhyan A, Vyas P, Sharma AK, Bishayee A (2020) Cancer chemoprevention by flavonoids, dietary polyphenols and terpenoids. Biointerface Res Appl Chem 11:8502–8537

    Article  Google Scholar 

  • Sheng ZZ (2020) Anticancer effects of catechin flavonoid in human glioma cells are mediated via autophagy induction, cell cycle arrest, inhibition of cell migration and invasion and targeting MAPK/ERK signalling pathway. J BU ON 25:1084–1090

    Google Scholar 

  • Sıdıka G, Cakir Z, Taghizadehghalehjoughi A, Yeşim Y, Jalili K, Hacimüftüoğlu A (2021) Investigation of the exosome-based drug delivery system potential in the treatment of glioblastoma in vitro experimental models. Int J Life Sci Biotechnol 4:451–467

    Article  Google Scholar 

  • Silantyev AS, Falzone L, Libra M, Gurina OI, Kardashova KS, Nikolouzakis TK, Nosyrev AE, Sutton CW, Mitsias PD, Tsatsakis A (2019) Current and future trends on diagnosis and prognosis of glioblastoma: from molecular biology to proteomics. Cells 8:863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 82:1807–1821

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh Tuli H, Kumar A, Ramniwas S, Coudhary R, Aggarwal D, Kumar M, Sharma U, Chaturvedi Parashar N, Haque S, Sak K (2022a) Ferulic acid: a natural phenol that inhibits neoplastic events through modulation of oncogenic signaling. Molecules 27:7653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singh Tuli H, Rath P, Chauhan A, Sak K, Aggarwal D, Choudhary R, Sharma U, Vashishth K, Sharma S, Kumar M (2022b) Luteolin, a potent anticancer compound: from chemistry to cellular interactions and synergetic perspectives. Cancers 14:5373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Singhal N, Selva-Nayagam S, Brown MP (2007) Prolonged and severe myelosuppression in two patients after low-dose temozolomide treatment-case study and review of literature. J Neurooncol 85:229–230

    Article  PubMed  CAS  Google Scholar 

  • Skotland T, Hessvik NP, Sandvig K, Llorente A (2019) Thematic review series: exosomes and microvesicles: Lipids as key components of their biogenesis and functions: exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology. J Lipid Res 60:9

    Article  PubMed  CAS  Google Scholar 

  • Smyth T, Petrova K, Payton NM, Persaud I, Redzic JS, Graner MW, Smith-Jones P, Anchordoquy TJ (2014) Surface functionalization of exosomes using click chemistry. Bioconjug Chem 25:1777–1784

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Soares JM, Faria BM, Ascari LM, Alves-Leon SV, Souza JM, Soares AG, Romao LF (2019) Diosmin induces caspase-dependent apoptosis in human glioblastoma cells. Anais da Academia Brasileira de Ciencias 91

  • Song Q, Peng S, Sun Z, Heng X, Zhu X (2021a) Temozolomide drives ferroptosis via a DMT1-dependent pathway in glioblastoma cells. Yonsei Med J 62:843

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Song H, Liu B, Dong B, Xu J, Zhou H, Na S, Liu Y, Pan Y, Chen F, Li L (2021b) Exosome-based delivery of natural products in cancer therapy. Front Cell Dev Biol 9:650426

    Article  PubMed  PubMed Central  Google Scholar 

  • Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  • Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212

    Article  PubMed  CAS  Google Scholar 

  • Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang H-G (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 18:1606–1614

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thakur A, Sidu RK, Gaurav I, Sweta K, Chakraborty P, Thakur S (2021) Modified biopolymer-based systems for drug delivery to the brain. Elsevier, In Tailor-Made and Functionalized Biopolymer Systems, pp 571–611

    Google Scholar 

  • Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579

    Article  PubMed  Google Scholar 

  • Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracellular Vesicles 7:1535750

    Article  Google Scholar 

  • Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, Wei J, Nie G (2014) A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35:2383–2390

    Article  PubMed  CAS  Google Scholar 

  • Tibensky M, Jakubechova J, Altanerova U, Pastorakova A, Rychly B, Baciak L, Mravec B, Altaner C (2022) Gene-directed enzyme/prodrug therapy of rat brain tumor mediated by human mesenchymal stem cell suicide gene extracellular vesicles in vitro and in vivo. Cancers 14:735

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trinh VA, Patel SP, Hwu WJ (2009) The safety of temozolomide in the treatment of malignancies. Exp Ppin Drug Saf 8(4):493-499

  • Tuli HS, Mittal S, Aggarwal D, Parashar G, Parashar NC, Upadhyay SK, Barwal TS, Jain A, Kaur G, Savla R (2021) Path of silibinin from diet to medicine: a dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance. In Proc Semin Cancer Biol 73:196–218

    Article  CAS  Google Scholar 

  • Tuli HS, Joshi H, Vashishth K, Ramniwas S, Varol M, Kumar M, Sak K (2023) Chemopreventive mechanisms of amentoflavone: recent trends and advancements. Naunyn-Schmiedeberg's Arch Pharmacol 396(5):865–876. https://doi.org/10.1007/s00210-023-02416-6

  • Valipour E, Ranjbar FE, Mousavi M, Ai J, Malekshahi ZV, Mokhberian N, Taghdiri-Nooshabadi Z, Khanmohammadi M, Nooshabadi VT (2022) The anti-angiogenic effect of atorvastatin loaded exosomes on glioblastoma tumor cells: an in vitro 3D culture model. Microvasc Res 143:104385

    Article  PubMed  CAS  Google Scholar 

  • Villano JL, Seery TE, Bressler LR (2009) Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64:647–655

    Article  PubMed  CAS  Google Scholar 

  • Vogiatzoglou A, Mulligan AA, Lentjes MA, Luben RN, Spencer JP, Schroeter H, Khaw K-T, Kuhnle GG (2015) Flavonoid intake in European adults (18 to 64 years). PLoS ONE 10:e0128132

    Article  PubMed  PubMed Central  Google Scholar 

  • Wahlgren J, Karlson TDL, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acid Res 40:130–130

    Article  Google Scholar 

  • Walle T (2007) Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Proc Semin Cancer Biol 17(5):354–362

    Article  CAS  Google Scholar 

  • Wang M, Altinoglu S, Takeda YS, Xu Q (2015) Integrating protein engineering and bioorthogonal click conjugation for extracellular vesicle modulation and intracellular delivery. PLoS ONE 10:e0141860

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang C, He C, Lu S, Wang X, Wang L, Liang S, Wang X, Piao M, Cui J, Chi G (2020) Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF. Cell Death Dis 11:630

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang H, Feng J, Ao F, Tang Y, Xu P, Wang M, Huang M (2021) Tumor-derived exosomal microRNA-7-5p enhanced by verbascoside inhibits biological behaviors of glioblastoma in vitro and in vivo. Mol Ther-Oncolytics 20:569–582

    Article  PubMed  CAS  Google Scholar 

  • Wang R, Liang Q, Zhang X, Di Z, Wang X, Di L (2022) Tumor-derived exosomes reversing TMZ resistance by synergistic drug delivery for glioma-targeting treatment. Colloids Surf, B 215:112505

    Article  CAS  Google Scholar 

  • Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R (2015) Glioma Nat Rev Dis Prim 1:1–18

    Google Scholar 

  • Wesolowski J, Rajdev P, Mukherji S (2010) Temozolomide (Temodar). Am J Neuroradiol 31:1383–1384

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu X, Wang X, Wang J, Hao Y, Liu F, Wang X, Yang L, Lu Z (2021) The roles of exosomes as future therapeutic agents and diagnostic tools for glioma. Front Oncol 11:733529

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu T, Liu Y, Cao Y, Liu Z (2022) Engineering macrophage exosome disguised biodegradable nanoplatform for enhanced sonodynamic therapy of glioblastoma. Adv Mater 34:2110364

    Article  CAS  Google Scholar 

  • Xie S, Zhang Q, Jiang L (2022) Current knowledge on exosome biogenesis, cargo-sorting mechanism and therapeutic implications. Membranes 12:498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xue Z, Tian L, Zheng H, Zhang Y, Song J (2022) Cyanidin inhibits glioma stem cells proliferation through the Wnt signaling pathway. Int J Neurosci: 1–8

  • Yan X, Hao Y, Chen S, Jia G, Guo Y, Zhang G, Wang C, Cheng R, Hu T, Zhang X (2005) Rutin induces apoptosis via P53 up-regulation in human glioma CHME cells. Transl Cancer Res 2019:8

    Google Scholar 

  • Yan Y, Liu X, Gao J, Wu Y, Li Y (2020) Inhibition of TGF-β signaling in gliomas by the flavonoid diosmetin isolated from Dracocephalum peregrinum L. Molecules 25:192

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, Yin VP, Lockman P, Bai S (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32:2003–2014

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yin J, Zeng A, Zhang Z, Shi Z, Yan W, You Y (2019) Exosomal transfer of miR-1238 contributes to temozolomide-resistance in glioblastoma. EBioMedicine 42:238–251

    Article  PubMed  PubMed Central  Google Scholar 

  • Youdim KA, Shukitt-Hale B, Joseph JA (2004) Flavonoids and the brain: interactions at the blood–brain barrier and their physiological effects on the central nervous system. Free Radical Biol Med 37:1683–1693

    Article  CAS  Google Scholar 

  • Yue B, Yang H, Wang J, Ru W, Wu J, Huang Y, Lan X, Lei C, Chen H (2020) Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis. Cell Prolif 53:e12857

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhai K, Mazurakova A, Koklesova L, Kubatka P, Büsselberg D (1841) Flavonoids synergistically enhance the anti-glioblastoma effects of chemotherapeutic drugs. Biomolecules 2021:11

    Google Scholar 

  • Zhai K, Brockmüller A, Kubatka P, Shakibaei M, Büsselberg D (2020) Curcumin’s beneficial effects on neuroblastoma: mechanisms, challenges, and potential solutions. Biomolecules 10:1469

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhai K, Siddiqui M, Abdellatif B, Liskova A, Kubatka P, Büsselberg D (2021) Natural compounds in glioblastoma therapy: preclinical insights, mechanistic pathways, and outlook. Cancers 13:2317

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhan Q, Yi K, Qi H, Li S, Li X, Wang Q, Wang Y, Liu C, Qiu M, Yuan X (2020) Engineering blood exosomes for tumor-targeting efficient gene/chemo combination therapy. Theranostics 10:7889

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhan Q, Yi K, Cui X, Li X, Yang S, Wang Q, Fang C, Tan Y, Li L, Xu C (2022) Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy. Neuro Oncol 24:1871–1883

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang J, Stevens FGM, Bradshaw DT (2012) Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharm 5:102–114

    Article  CAS  Google Scholar 

  • Zhang Y, Liu Y, Liu H, Tang WH (2019) Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 9:1–18

    Article  Google Scholar 

  • Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P (2020) Exosome: a review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. International J Nanomedicine 6917–6934

  • Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19:1769–1779

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L (2012) Corrigendum: treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 20:239

    Article  CAS  Google Scholar 

  • Zou Y, Wang Y, Xu S, Liu Y, Yin J, Lovejoy DB, Zheng M, Liang XJ, Park JB, Efremov YM (2022) Brain co-delivery of temozolomide and cisplatin for combinatorial glioblastoma chemotherapy. Adv Mater 34:2203958

    Article  CAS  Google Scholar 

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Acknowledgements

Authors are gratefully acknowledged by Sir Ganga Ram Hospital, Delhi, India for providing necessary support. Dr. T.S., would like to acknowledge ICMRDHR, Government of India (ICMR-DHR Young ScientistFellowship, F.NO: R. 12014/29/2022/HR), and college Research and Development Cell (RDC) Scheme (Fileno. HRC/RDC/2021/RP/13).

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Authors and Affiliations

  1. Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, India

    Priyanka Verma, Bunty Sharma & Hardeep Singh Tuli

  2. School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India

    Hemant Joshi

  3. Translational Oncology Laboratory, Department of Zoology, Hansraj College, Delhi University, New Delhi, 110007, India

    Tejveer Singh

  4. Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bhatinda, 151001, India

    Ujjawal Sharma

  5. University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali, 140413, India

    Seema Ramniwas

  6. Department of Research, Sir Ganga Ram Hospital, New Delhi, 122016, India

    Rashmi Rana

  7. Department of Pharmaceutics, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, India

    Madhu Gupta

  8. Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’S NMIMS, Vile Parle-West, Mumbai, 400056, India

    Ginpreet Kaur

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  1. Priyanka Verma
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Contributions

Conceptualization, methodology, validation, writing - review, H.S.T., H.J., T.S., B.S., U.S., S.R., and R.R.; formal analysis, resources, R.R., and M.G.; data curation, G.K., All authors have read and agreed to the published version of the manuscript. The authors confirm that no paper mill and artificial intelligence was used.

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Verma, P., Joshi, H., Singh, T. et al. Temozolomide and flavonoids against glioma: from absorption and metabolism to exosomal delivery. Naunyn-Schmiedeberg's Arch Pharmacol 397, 41–57 (2024). https://doi.org/10.1007/s00210-023-02660-w

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