Skip to main content
Log in

Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy

细胞周期调控与化疗共给药策略在癌症治疗中的应用

  • Review
  • Published:
Science China Materials Aims and scope Submit manuscript

Abstract

Combination chemotherapy is widely exploited to overcome multidrug resistance (MDR) and enhance the therapeutic effect of anti-tumor agents clinically. The traditional combination regimens applied in clinical practice still suffer from various obstacles, such as inevitable side effects. Fortunately, the application of nanotechnology and the proposal of co-delivery systems make the combination therapy more effective. The occurrence, development, and metastasis of tumors are closely related to the cell cycle. The sensitivity of tumor cells to chemotherapeutic drugs can be improved with the cooperation of cell cycle regulators. In this review, the influence of the cell cycle on tumorigenesis and development is introduced briefly. The current strategies of combining chemotherapeutic drugs and cell cycle regulators through co-delivery systems are discussed in detail. We also sketch the possibility of treating tumors mildly via artificially controlling the cell cycle and outline the challenges and perspectives about the improvement of co-delivery systems for cancer therapy.

摘要

联合化疗是临床上用于克服肿瘤多药耐药性、 提高肿瘤治疗效果的常用策略. 然而在临床上, 传统的联合用药仍存在诸多缺陷, 如不可避免的副作用. 纳米技术的应用和多药共同递送体系的提出使联合治疗的治疗效果得以显著提升. 肿瘤的发生、 发展和转移与细胞周期密切相关. 因此, 在化疗过程中配合使用细胞周期调节剂可以增强肿瘤细胞对化疗药物的敏感性. 本综述首先简要介绍了细胞周期对肿瘤发生和发展的影响, 然后详细讨论了目前通过多药共同递送体系结合化疗药物和细胞周期调节剂的一系列策略. 最后, 我们总结概述了通过调控细胞周期进行肿瘤治疗的挑战和前景.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Randrian V, Biau J, Benoît C, et al. Radiothérapie avec modulation d’intensité préopératoire des cancers rectaux: Intérêt et application. Cancer/Radiothérapie, 2020, 24: 345–353

    Article  CAS  Google Scholar 

  2. Kumari P, Ghosh B, Biswas S. Nanocarriers for cancer-targeted drug delivery. J Drug Targeting, 2016, 24: 179–191

    Article  CAS  Google Scholar 

  3. Liu YL, Chen D, Shang P, et al. A review of magnet systems for targeted drug delivery. J Control Release, 2019, 302: 90–104

    Article  CAS  Google Scholar 

  4. Abdelaziz HM, Gaber M, Abd-Elwakil MM, et al. Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates. J Control Release, 2018, 269: 374–392

    Article  CAS  Google Scholar 

  5. Qin T, Xu X, Zhang Z, et al. Paclitaxel/sunitinib-loaded micelles promote an antitumor response in vitro through synergistic immunogenic cell death for triple-negative breast cancer. Nanotechnology, 2020, 31: 365101

    Article  CAS  Google Scholar 

  6. Levit SL, Yang H, Tang C. Rapid self-assembly of polymer nanoparticles for synergistic codelivery of paclitaxel and lapatinib via flash nanoprecipitation. Nanomaterials, 2020, 10: 561

    Article  CAS  Google Scholar 

  7. Xiong Y, Zhao Y, Miao L, et al. Co-delivery of polymeric metformin and cisplatin by self-assembled core-membrane nanoparticles to treat non-small cell lung cancer. J Control Release, 2016, 244: 63–73

    Article  CAS  Google Scholar 

  8. Rozengurt E. Autocrine loops, signal transduction, and cell cycle abnormalities in the molecular biology of lung cancer. Curr Opin Oncology, 1999, 11: 116–122

    Article  CAS  Google Scholar 

  9. Ocio EM, Richardson PG, Rajkumar SV, et al. New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the international myeloma working group (IMWG). Leukemia, 2014, 28: 525–542

    Article  CAS  Google Scholar 

  10. Zhang X, Xia Q, Wei R, et al. Melatonin protects spermatogonia from the stress of chemotherapy and oxidation via eliminating reactive oxidative species. Free Radical Biol Med, 2019, 137: 74–86

    Article  CAS  Google Scholar 

  11. Ferraro G, Loreto D, Merlino A. Interaction of platinum-based drugs with proteins: An overview of representative crystallographic studies. Curr Topics Med Chem, 2021, 21: 6–27

    Article  CAS  Google Scholar 

  12. Zhou SF, Wang LL, Di YM, et al. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem, 2008, 15: 1981–2039

    Article  CAS  Google Scholar 

  13. Yang L, Wang B, Qiao W, et al. A novel combination chemotherapy integrating with intratumoral chemotherapy. Med Hypotheses, 2009, 73: 334–335

    Article  CAS  Google Scholar 

  14. Sarraf CE, Ansari TW, Conway P, et al. Bromodeoxyuridine-labelled apoptosis after treatment with antimetabolites in two murine tumours and in small intestinal crypts. Br J Cancer, 1993, 68: 678–680

    Article  CAS  Google Scholar 

  15. Wang X, Tanaka M, Krstin S, et al. The interference of selected cytotoxic alkaloids with the cytoskeleton: An insight into their modes of action. Molecules, 2016, 21: 906

    Article  Google Scholar 

  16. Meng QY, Cong HL, Hu H, et al. Rational design and latest advances of codelivery systems for cancer therapy. Mater Today Bio, 2020, 7: 100056

    Article  CAS  Google Scholar 

  17. Xin ZH, Meng YL, Jiang WJ, et al. Finding an efficient tetramethylated hydroxydiethylene of resveratrol analogue for potential anticancer agent. BMC Chem, 2020, 14: 13

    Article  Google Scholar 

  18. Yu X, Li S. Non-metabolic functions of glycolytic enzymes in tumorigenesis. Oncogene, 2017, 36: 2629–2636

    Article  CAS  Google Scholar 

  19. Kunnumakkara AB, Bordoloi D, Harsha C, et al. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways. Clin Sci, 2017, 131: 1781–1799

    Article  CAS  Google Scholar 

  20. Concato VM, Tomiotto-Pellissier F, Silva TF, et al. 3,3′,5,5′-tetramethoxybiphenyl-4,4′-diol induces cell cycle arrest in G2/M phase and apoptosis in human non-small cell lung cancer A549 cells. Chemico-Biol Interact, 2020, 326: 109133

    Article  CAS  Google Scholar 

  21. Zhang F, Zhang YY, Sun YS, et al. Asparanin A from Asparagus officinalis L. induces G0/G1 cell cycle arrest and apoptosis in human endometrial carcinoma Ishikawa cells via mitochondrial and PI3K/AKT signaling pathways. J Agric Food Chem, 2020, 68: 213–224

    Article  CAS  Google Scholar 

  22. Vessella RL, Pantel K, Mohla S. Tumor cell dormancy: An NCI workshop report. Cancer Biol Ther, 2007, 6: 1492–1500

    Article  Google Scholar 

  23. Zhou Y, Liu Q, Dai X, et al. Transdifferentiation of type II alveolar epithelial cells induces reactivation of dormant tumor cells by enhancing TGF-β1/SNAI2 signaling. Oncol Rep, 2018, 39: 1874–1882

    CAS  Google Scholar 

  24. Nie J, Liu L, Zheng W, et al. MicroRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting cyclin D1 and Bcl-2. Carcinogenesis, 2012, 33: 220–225

    Article  CAS  Google Scholar 

  25. Xia X, Yu Y, Zhang L, et al. Inhibitor of DNA binding 1 regulates cell cycle progression of endothelial progenitor cells through induction of Wnt2 expression. Mol Med Rep, 2016, 14: 2016–2024

    Article  CAS  Google Scholar 

  26. Zhu D, Yuan Y, Qiao J, et al. Enhanced anticancer activity of a protein phosphatase 2A inhibitor on chemotherapy and radiation in head and neck squamous cell carcinoma. Cancer Lett, 2015, 356: 773–780

    Article  CAS  Google Scholar 

  27. de Jong Y, Bennani F, van Oosterwijk JG, et al. A screening-based approach identifies cell cycle regulators AURKA, CHK1 and PLK1 as targetable regulators of chondrosarcoma cell survival. J Bone Oncol, 2019, 19: 100268

    Article  Google Scholar 

  28. Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, et al. Targeting cell cycle regulation in cancer therapy. Pharmacol Therapeut, 2013, 138: 255–271

    Article  CAS  Google Scholar 

  29. Lim S, Kaldis P. Cdks, cyclins and CKIs: Roles beyond cell cycle regulation. Development, 2013, 140: 3079–3093

    Article  CAS  Google Scholar 

  30. Qie S, Diehl JA. Cyclin D1, cancer progression, and opportunities in cancer treatment. J Mol Med, 2016, 94: 1313–1326

    Article  CAS  Google Scholar 

  31. Murray AW. Recycling the cell cycle. Cell, 2004, 116: 221–234

    Article  CAS  Google Scholar 

  32. Elledge SJ. Cell cycle checkpoints: Preventing an identity crisis. Science, 1996, 274: 1664–1672

    Article  CAS  Google Scholar 

  33. Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, et al. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem, 2004, 73: 39–85

    Article  CAS  Google Scholar 

  34. Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med, 2006, 12: 440–450

    Article  CAS  Google Scholar 

  35. Khan H, Reale M, Ullah H, et al. Anti-cancer effects of polyphenols via targeting p53 signaling pathway: Updates and future directions. Biotech Adv, 2020, 38: 107385

    Article  CAS  Google Scholar 

  36. Guille A, Chaffanet M, Birnbaum D. Signaling pathway switch in breast cancer. Cancer Cell Int, 2013, 13: 66

    Article  CAS  Google Scholar 

  37. Wu Y, Ma J, Sun Y, et al. Effect and mechanism of PI3K/AKT/mTOR signaling pathway in the apoptosis of GC-1 cells induced by nickel nanoparticles. Chemosphere, 2020, 255: 126913

    Article  CAS  Google Scholar 

  38. Yu Q, Zeng KW, Ma XL, et al. Resokaempferol-mediated anti-inflammatory effects on activated macrophages via the inhibition of JAK2/STAT3, NF-κB and JNK/p38 MAPK signaling pathways. Int Immunopharmacol, 2016, 38: 104–114

    Article  CAS  Google Scholar 

  39. O’Shea JJ, Schwartz DM, Villarino AV, et al. The JAK-STAT pathway: Impact on human disease and therapeutic intervention. Annu Rev Med, 2015, 66: 311–328

    Article  Google Scholar 

  40. Huang L, Shan YJ, He CX, et al. Effects of L. paracasei subp. paracasei X12 on cell cycle of colon cancer HT-29 cells and regulation of mTOR signalling pathway. J Funct Foods, 2016, 21: 431–439

    Article  CAS  Google Scholar 

  41. Elliott B, Millena AC, Matyunina L, et al. Essential role of jund in cell proliferation is mediated via Myc signaling in prostate cancer cells. Cancer Lett, 2019, 448: 155–167

    Article  CAS  Google Scholar 

  42. Moloney JN, Cotter TG. ROS signalling in the biology of cancer. Seminars Cell Dev Biol, 2018, 80: 50–64

    Article  CAS  Google Scholar 

  43. Felty Q, Singh KP, Roy D. Estrogen-induced G1/S transition of G0-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling. Oncogene, 2005, 24: 4883–4893

    Article  CAS  Google Scholar 

  44. Liou GY, Storz P. Reactive oxygen species in cancer. Free Radical Res, 2010, 44: 479–496

    Article  CAS  Google Scholar 

  45. Marsh JC. The effects of cancer chemotherapeutic agents on normal hematopoietic precursor cells: A review. Cancer Res, 1976, 36: 1853–1882

    CAS  Google Scholar 

  46. Cao R, Peng W, Wang Z, et al. β-Carboline alkaloids: Biochemical and pharmacological functions. Curr Med Chem, 2007, 14: 479–500

    Article  CAS  Google Scholar 

  47. Fu D, Calvo JA, Samson LD. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer, 2012, 12: 104–120

    Article  CAS  Google Scholar 

  48. Khoury A, Deo KM, Aldrich-Wright JR. Recent advances in platinum-based chemotherapeutics that exhibit inhibitory and targeted mechanisms of action. J Inorg Biochem, 2020, 207: 111070

    Article  CAS  Google Scholar 

  49. Ataei S, Yilmaz S, Ertan-Bolelli T, et al. Generated 3D-common feature hypotheses using the hiphop method for developing new topoisomerase I inhibitors. Arch Pharm Chem Life Sci, 2015, 348: 498–507

    Article  CAS  Google Scholar 

  50. Coussy F, El-Botty R, Château-Joubert S, et al. BrCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers. Sci Transl Med, 2020, 12: eaax2625

    Article  CAS  Google Scholar 

  51. Kim GM, Kim YS, Ae Kang Y, et al. Efficacy and toxicity of belotecan for relapsed or refractory small cell lung cancer patients. J Thorac Oncol, 2012, 7: 731–736

    Article  CAS  Google Scholar 

  52. Pommier Y. Topoisomerase I inhibitors: Camptothecins and beyond. Nat Rev Cancer, 2006, 6: 789–802

    Article  CAS  Google Scholar 

  53. Ma P, Xiao H, Yu C, et al. Enhanced cisplatin chemotherapy by iron oxide nanocarrier-mediated generation of highly toxic reactive oxygen species. Nano Lett, 2017, 17: 928–937

    Article  CAS  Google Scholar 

  54. Noh J, Kwon B, Han E, et al. Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death. Nat Commun, 2015, 6: 6907

    Article  CAS  Google Scholar 

  55. Costi MP, Tondi D, Rinaldi M, et al. Structure-based studies on species-specific inhibition of thymidylate synthase. Biochim Biophys Acta (BBA)-Mol Basis Dis, 2002, 1587: 206–214

    Article  CAS  Google Scholar 

  56. Longley DB, Harkin DP, Johnston PG. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer, 2003, 3: 330–338

    Article  CAS  Google Scholar 

  57. Adjei AA. Pemetrexed (ALIMTA), a novel multitargeted anti-neoplastic agent. Clin Cancer Res, 2004, 10: 4276s-4280s

    Article  Google Scholar 

  58. Abali EE, Skacel NE, Celikkaya H, et al. Regulation of human dihydrofolate reductase activity and expression. Vitam Horm, 2008, 79: 267

    Article  CAS  Google Scholar 

  59. Raimondi MV, Randazzo O, La Franca M, et al. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules, 2019, 24: 1140

    Article  Google Scholar 

  60. Zhang L, Guo J, Jiang XM, et al. Identification of nagilactone E as a protein synthesis inhibitor with anticancer activity. Acta Pharmacol Sin, 2020, 41: 698–705

    Article  CAS  Google Scholar 

  61. Ferreira R, Schneekloth Jr. JS, Panov KI, et al. Targeting the RNA polymerase I transcription for cancer therapy comes of age. Cells, 2020, 9: 266

    Article  CAS  Google Scholar 

  62. Chand S, Mahajan RV, Prasad JP, et al. A comprehensive review on microbial L-asparaginase: Bioprocessing, characterization, and industrial applications. Biotech Appl Biochem, 2020, 67: 619–647

    Article  CAS  Google Scholar 

  63. Battogtokh G, Choi YS, Kang DS, et al. Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: Current strategies and future perspectives. Acta Pharm Sin B, 2018, 8: 862–880

    Article  Google Scholar 

  64. Mordente A, Meucci E, Silvestrini A, et al. Anthracyclines and mitochondria. Adv Exp Med Biol, 2012, 942: 385–419

    Article  CAS  Google Scholar 

  65. Gilles A, Frechin L, Natchiar K, et al. Targeting the human 80s ribosome in cancer: From structure to function and drug design for innovative adjuvant therapeutic strategies. Cells, 2020, 9: 629

    Article  CAS  Google Scholar 

  66. Burger K, Mühl B, Harasim T, et al. Chemotherapeutic drugs inhibit ribosome biogenesis at various levels. J Biol Chem, 2010, 285: 12416–12425

    Article  CAS  Google Scholar 

  67. Al-Wadei HAN, Al-Wadei MH, Ullah MF, et al. Celecoxib and GABA cooperatively prevent the progression of pancreatic cancer in vitro and in xenograft models of stress-free and stress-exposed mice. PLoS ONE, 2012, 7: e43376

    Article  CAS  Google Scholar 

  68. Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem, 2000, 275: 11397–11403

    Article  CAS  Google Scholar 

  69. Fukunaga T, Nagahama M, Hatsuzawa K, et al. Implication of sphingolipid metabolism in the stability of the golgi apparatus. J Cell Sci, 2000, 113: 3299–3307

    Article  CAS  Google Scholar 

  70. Crespo I, San-Miguel B, Prause C, et al. Glutamine treatment attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis. PLoS ONE, 2012, 7: e50407

    Article  CAS  Google Scholar 

  71. Peng C, Zhao Y, Hao Y, et al. Syk expression in non-small-cell lung cancer and its relation with angiogenesis. J Can Res Ther, 2016, 12: 663–666

    Article  CAS  Google Scholar 

  72. Ye W. The complexity of translating anti-angiogenesis therapy from basic science to the clinic. Dev Cell, 2016, 37: 114–125

    Article  CAS  Google Scholar 

  73. Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature, 2005, 438: 967–974

    Article  CAS  Google Scholar 

  74. Yang JI, Jin B, Kim SY, et al. Antitumour effects of liporaxel (oral paclitaxel) for canine melanoma in a mouse xenograft model. Vet Comp Oncol, 2020, 18: 152–160

    Article  CAS  Google Scholar 

  75. Gao P, Wang LL, Liu J, et al. Dihydroartemisinin inhibits endothelial cell tube formation by suppression of the STAT3 signaling pathway. Life Sci, 2020, 242: 117221

    Article  Google Scholar 

  76. Van der Veldt AAM, Lubberink M, Bahce I, et al. Rapid decrease in delivery of chemotherapy to tumors after anti-VEGF therapy: Implications for scheduling of anti-angiogenic drugs. Cancer Cell, 2012, 21: 82–91

    Article  CAS  Google Scholar 

  77. Yang WH, Xu J, Mu JB, et al. Revision of the concept of anti-angiogenesis and its applications in tumor treatment. Chronic Dis Transl Med, 2017, 3: 33–40

    Google Scholar 

  78. Freund E, Liedtke KR, Miebach L, et al. Identification of two kinase inhibitors with synergistic toxicity with low-dose hydrogen peroxide in colorectal cancer cells in vitro. Cancers, 2020, 12: 122

    Article  CAS  Google Scholar 

  79. Sun M, He L, Fan Z, et al. Effective treatment of drug-resistant lung cancer via a nanogel capable of reactivating cisplatin and enhancing early apoptosis. Biomaterials, 2020, 257: 120252

    Article  CAS  Google Scholar 

  80. Deneka AY, Einarson MB, Bennett J, et al. Synthetic lethal targeting of mitotic checkpoints in HPV-negative head and neck cancer. Cancers, 2020, 12: 306

    Article  CAS  Google Scholar 

  81. Cong Y, Xiao H, Xiong H, et al. Dual drug backboned shattering polymeric theranostic nanomedicine for synergistic eradication of patient-derived lung cancer. Adv Mater, 2018, 30: 1706220

    Article  Google Scholar 

  82. Moghaddam SV, Abedi F, Alizadeh E, et al. Lysine-embedded cellulose-based nanosystem for efficient dual-delivery of chemotherapeutics in combination cancer therapy. Carbohydr Polym, 2020, 250: 116861

    Article  CAS  Google Scholar 

  83. Zhang M, Hagan Iv CT, Min Y, et al. Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models. Biomaterials, 2018, 169: 1–10

    Article  CAS  Google Scholar 

  84. Rui M, Xin Y, Li R, et al. Targeted biomimetic nanoparticles for synergistic combination chemotherapy of paclitaxel and doxorubicin. Mol Pharm, 2017, 14: 107–123

    Article  CAS  Google Scholar 

  85. Li X, Diao W, Xue H, et al. Improved efficacy of doxorubicin delivery by a novel dual-ligand-modified liposome in hepatocellular carcinoma. Cancer Lett, 2020, 489: 163–173

    Article  CAS  Google Scholar 

  86. Alle M, G BR, Kim TH, et al. Doxorubicin-carboxymethyl xanthan gum capped gold nanoparticles: Microwave synthesis, characterization, and anti-cancer activity. Carbohydr Polym, 2020, 229: 115511

    Article  CAS  Google Scholar 

  87. Gothwal A, Khan I, Gupta U. Polymeric micelles: Recent advancements in the delivery of anticancer drugs. Pharm Res, 2016, 33: 18–39

    Article  CAS  Google Scholar 

  88. Li I, Nabet BY. Exosomes in the tumor microenvironment as mediators of cancer therapy resistance. Mol Cancer, 2019, 18: 32

    Article  Google Scholar 

  89. Liang Y, Zhao X, Ma PX, et al. pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan for localized drug delivery. J Colloid Interface Sci, 2019, 536: 224–234

    Article  CAS  Google Scholar 

  90. Nosrati H, Adinehvand R, Manjili HK, et al. Synthesis, characterization, and kinetic release study of methotrexate loaded mPEG-PCL polymersomes for inhibition of MCF-7 breast cancer cell line. Pharm Dev Tech, 2019, 24: 89–98

    Article  CAS  Google Scholar 

  91. Qian Q, Zhu L, Zhu X, et al. Drug-polymer hybrid macro-molecular engineering: Degradable PEG integrated by platinum (IV) for cancer therapy. Matter, 2019, 1: 1618–1630

    Article  Google Scholar 

  92. Meng J, Agrahari V, Youm I. Advances in targeted drug delivery approaches for the central nervous system tumors: The inspiration of nanobiotechnology. J Neuroimmune Pharmacol, 2017, 12: 84–98

    Article  Google Scholar 

  93. Fumoto S, Nishida K. Co-delivery systems of multiple drugs using nanotechnology for future cancer therapy. Chem Pharm Bull, 2020, 68: 603–612

    Article  CAS  Google Scholar 

  94. Kommineni N, Mahira S, Domb AJ, et al. Cabazitaxel-loaded nanocarriers for cancer therapy with reduced side effects. Pharmaceutics, 2019, 11: 141

    Article  CAS  Google Scholar 

  95. Soe ZC, Kwon JB, Thapa RK, et al. Transferrin-conjugated polymeric nanoparticle for receptor-mediated delivery of doxorubicin in doxorubicin-resistant breast cancer cells. Pharmaceutics, 2019, 11: 63

    Article  CAS  Google Scholar 

  96. Wang Y, Ding Y, Xu Y, et al. Mixed micelles of TPGS and Soluplus® for co-delivery of paclitaxel and fenretinide: In vitro and in vivo anticancer study. Pharm Dev Tech, 2020, 25: 865–873

    Article  CAS  Google Scholar 

  97. Rawal S, Patel MM. Threatening cancer with nanoparticle aided combination oncotherapy. J Control Release, 2019, 301: 76–109

    Article  CAS  Google Scholar 

  98. Qiao Y, Huang X, Nimmagadda S, et al. A robust approach to enhance tumor-selective accumulation of nanoparticles. Oncotarget, 2011, 2: 59–68

    Article  Google Scholar 

  99. Allen TM, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliver Rev, 2013, 65: 36–48

    Article  CAS  Google Scholar 

  100. Sawant RR, Torchilin VP. Challenges in development of targeted liposomal therapeutics. AAPS J, 2012, 14: 303–315

    Article  CAS  Google Scholar 

  101. Zeng F, Ju RJ, Liu L, et al. Efficacy in treating lung metastasis of invasive breast cancer with functional vincristine plus dasatinib liposomes. Pharmacology, 2018, 101: 43–53

    Article  Google Scholar 

  102. Li C, Han X. Melanoma cancer immunotherapy using PD-L1 siRNA and imatinib promotes cancer-immunity cycle. Pharm Res, 2020, 37: 109

    Article  CAS  Google Scholar 

  103. Kumar S, Sharma AR, Sharma G, et al. PLK-1: Angel or devil for cell cycle progression. Biochim Biophys Acta (BBA)-Rev Cancer, 2016, 1865: 190–203

    Article  CAS  Google Scholar 

  104. Sizek H, Hamel A, Deritei D, et al. Boolean model of growth signaling, cell cycle and apoptosis predicts the molecular mechanism of aberrant cell cycle progression driven by hyperactive PI3K. PLoS Comput Biol, 2019, 15: e1006402

    Article  Google Scholar 

  105. Bulbake U, Kommineni N, Bryszewska M, et al. Cationic liposomes for co-delivery of paclitaxel and anti-PLK1 siRNA to achieve enhanced efficacy in breast cancer. J Drug Deliver Sci Tech, 2018, 48: 253–265

    Article  CAS  Google Scholar 

  106. Li RJ, Ying X, Zhang Y, et al. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells. J Control Release, 2011, 149: 281–291

    Article  CAS  Google Scholar 

  107. Mohan A, Narayanan S, Balasubramanian G, et al. Dual drug loaded nanoliposomal chemotherapy: A promising strategy for treatment of head and neck squamous cell carcinoma. Eur J Pharm Biopharm, 2016, 99: 73–83

    Article  CAS  Google Scholar 

  108. Soe ZC, Thapa RK, Ou W, et al. Folate receptor-mediated celastrol and irinotecan combination delivery using liposomes for effective chemotherapy. Colloids Surfs B-Biointerfaces, 2018, 170: 718–728

    Article  CAS  Google Scholar 

  109. Ou H, Li J, Chen C, et al. Organic/polymer photothermal nanoagents for photoacoustic imaging and photothermal therapy in vivo. Sci China Mater, 2019, 62: 1740–1758

    Article  CAS  Google Scholar 

  110. Aghebati-Maleki A, Dolati S, Ahmadi M, et al. Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers. J Cell Physiol, 2020, 235: 1962–1972

    Article  CAS  Google Scholar 

  111. Sun Q, Zhou Z, Qiu N, et al. Rational design of cancer nanomedicine: Nanoproperty integration and synchronization. Adv Mater, 2017, 29: 1606628

    Article  Google Scholar 

  112. Qin SY, Zhang AQ, Cheng SX, et al. Drug self-delivery systems for cancer therapy. Biomaterials, 2017, 112: 234–247

    Article  CAS  Google Scholar 

  113. Chen J, Yang X, Huang L, et al. Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy. Drug Deliver, 2018, 25: 1932–1942

    Article  CAS  Google Scholar 

  114. Rezvantalab S, Drude NI, Moraveji MK, et al. PLGA-based nanoparticles in cancer treatment. Front Pharmacol, 2018, 9: 1260

    Article  CAS  Google Scholar 

  115. Khan I, Joshi G, Nakhate KT, et al. Nano-co-delivery of berberine and anticancer drug using PLGA nanoparticles: Exploration of better anticancer activity and in vivo kinetics. Pharm Res, 2019, 36: 149

    Article  Google Scholar 

  116. Mohammed AFA, Higashi T, Motoyama K, et al. In vitro and in vivo co-delivery of siRNA and doxorubicin by folate-PEG-appended dendrimer/glucuronylglucosyl-β-cyclodextrin conjugate. AAPS J, 2019, 21: 54

    Article  Google Scholar 

  117. Ji Y, Liu X, Li J, et al. Use of ratiometrically designed nanocarrier targeting CDK4/6 and autophagy pathways for effective pancreatic cancer treatment. Nat Commun, 2020, 11: 4249

    Article  CAS  Google Scholar 

  118. Wang S, Liu X, Chen S, et al. Regulation of Ca2+ signaling for drug-resistant breast cancer therapy with mesoporous silica nanocapsule encapsulated doxorubicin/siRNA cocktail. ACS Nano, 2019, 13: 274–283

    Article  CAS  Google Scholar 

  119. Chen F, Zhang H, Jiang L, et al. Enhancing the cytotoxic efficacy of combined effect of doxorubicin and cyclosporin encapsulated photoluminescent graphene dotted mesoporous nanoparticles against lung cancer cell-specific drug targeting for the nursing care of cancer patients. J Photochem Photobiol B-Biol, 2019, 198: 111578

    Article  CAS  Google Scholar 

  120. Du X, Zhang T, Ma G, et al. Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy. Int J Nanomed, 2019, Volume 14: 2233–2251

    Article  CAS  Google Scholar 

  121. Cagel M, Tesan FC, Bernabeu E, et al. Polymeric mixed micelles as nanomedicines: Achievements and perspectives. Eur J Pharm Biopharm, 2017, 113: 211–228

    Article  CAS  Google Scholar 

  122. Banala VT, Urandur S, Sharma S, et al. Targeted co-delivery of the aldose reductase inhibitor epalrestat and chemotherapeutic doxorubicin via a redox-sensitive prodrug approach promotes synergistic tumor suppression. Biomater Sci, 2019, 7: 2889–2906

    Article  CAS  Google Scholar 

  123. Chen Y, Zhang W, Huang Y, et al. Pluronic-based functional polymeric mixed micelles for co-delivery of doxorubicin and paclitaxel to multidrug resistant tumor. Int J Pharm, 2015, 488: 44–58

    Article  CAS  Google Scholar 

  124. Debele TA, Yu LY, Yang CS, et al. pH- and GSH-sensitive hyaluronic acid-MP conjugate micelles for intracellular delivery of doxorubicin to colon cancer cells and cancer stem cells. Biomacromolecules, 2018, 19: 3725–3737

    Article  CAS  Google Scholar 

  125. Han NN, Li X, Tao L, et al. Doxorubicin and rhein loaded nanomicelles attenuates multidrug resistance in human ovarian cancer. Biochem Biophys Res Commun, 2018, 498: 178–185

    Article  CAS  Google Scholar 

  126. Srisa-Nga K, Mankhetkorn S, Okonogi S, et al. Delivery of super-paramagnetic polymeric micelles loaded with quercetin to hepatocellular carcinoma cells. J Pharm Sci, 2019, 108: 996–1006

    Article  CAS  Google Scholar 

  127. Narayanaswamy R, Torchilin VP. Hydrogels and their applications in targeted drug delivery. Molecules, 2019, 24: 603

    Article  Google Scholar 

  128. Li Z, Guan J. Thermosensitive hydrogels for drug delivery. Expert Opin Drug Deliver, 2011, 8: 991–1007

    Article  CAS  Google Scholar 

  129. Lv Q, He C, Quan F, et al. DOX/IL-2/IFN-γ co-loaded thermosensitive polypeptide hydrogel for efficient melanoma treatment. Bioactive Mater, 2018, 3: 118–128

    Article  Google Scholar 

  130. Karavasili C, Andreadis DA, Katsamenis OL, et al. Synergistic antitumor potency of a self-assembling peptide hydrogel for the local co-delivery of doxorubicin and curcumin in the treatment of head and neck cancer. Mol Pharm, 2019, 16: 2326–2341

    Article  CAS  Google Scholar 

  131. Wu X, Wu Y, Ye H, et al. Interleukin-15 and cisplatin co-encapsulated thermosensitive polypeptide hydrogels for combined immuno-chemotherapy. J Control Release, 2017, 255: 81–93

    Article  CAS  Google Scholar 

  132. Wu X, He C, Wu Y, et al. Synergistic therapeutic effects of Schiff’s base cross-linked injectable hydrogels for local co-delivery of metformin and 5-fluorouracil in a mouse colon carcinoma model. Biomaterials, 2016, 75: 148–162

    Article  CAS  Google Scholar 

  133. Ma H, He C, Cheng Y, et al. PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment. Biomaterials, 2014, 35: 8723–8734

    Article  CAS  Google Scholar 

  134. Liu C, Su C. Design strategies and application progress of therapeutic exosomes. Theranostics, 2019, 9: 1015–1028

    Article  CAS  Google Scholar 

  135. Luan X, Sansanaphongpricha K, Myers I, et al. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin, 2017, 38: 754–763

    Article  CAS  Google Scholar 

  136. Liang G, Zhu Y, Ali DJ, et al. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J Nanobiotechnol, 2020, 18: 10

    Article  CAS  Google Scholar 

  137. Sharma AK, Prasher P, Aljabali AA, et al. Emerging era of “somes”: Polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy. Drug Deliv Transl Res, 2020, 10: 1171–1190

    Article  CAS  Google Scholar 

  138. Qin Y, Zhang Z, Huang C, et al. Folate-targeted redox-responsive polymersomes loaded with chemotherapeutic drugs and tariquidar to overcome drug resistance. J Biomed Nanotechnol, 2018, 14: 1705–1718

    Article  CAS  Google Scholar 

  139. Aarts M, Linardopoulos S, Turner NC. Tumour selective targeting of cell cycle kinases for cancer treatment. Curr Opin Pharmacol, 2013, 13: 529–535

    Article  CAS  Google Scholar 

  140. Huang J, Ji G, Xing L, et al. Neo-endocrinochemotherapy: A novel approach for enhancing chemotherapeutic efficacy in clinic? Med Hypotheses, 2013, 80: 441–446

    Article  CAS  Google Scholar 

  141. Huang J, Jin L, Ji G, et al. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: Chemosensitization role of triiodothyronine. BMC Cancer, 2013, 13: 334

    Article  CAS  Google Scholar 

  142. Conzemius MG, Graham JC, Haynes JS, et al. Effects of treatment with growth hormone and somatostatin on efficacy of diammine [1,1-cyclobutane dicarboxylato (2-)-0,0’]-(SP-4-2) in athymic rats with osteosarcoma. Am J Vet Res, 2000, 61: 646–650

    Article  CAS  Google Scholar 

  143. Zou K, Ju JH, Xie H. Pretreatment with insulin enhances anticancer functions of 5-fluorou-racil in human esophageal and colonic cancer cells. Acta Pharmacol Sin, 2007, 28: 721–730

    Article  CAS  Google Scholar 

  144. Ijichi K, Adachi M, Ogawa T, et al. Cell-cycle distribution and thymidilate synthatase (TS) expression correlate with 5-FU resistance in head and neck carcinoma cells. Anticancer Res, 2014, 34: 2907–2911

    CAS  Google Scholar 

  145. Reinhardt HC, Aslanian AS, Lees JA, et al. P53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell, 2007, 11: 175–189

    Article  CAS  Google Scholar 

  146. Murrow LM, Garimella SV, Jones TL, et al. Identification of WEE1 as a potential molecular target in cancer cells by RNAi screening of the human tyrosine kinome. Breast Cancer Res Treat, 2010, 122: 347–357

    Article  CAS  Google Scholar 

  147. Jin J, Fang H, Yang F, et al. Combined inhibition of ATR and WEE1 as a novel therapeutic strategy in triple-negative breast cancer. Neoplasia, 2018, 20: 478–488

    Article  CAS  Google Scholar 

  148. Sen T, Della Corte CM, Milutinovic S, et al. Combination treatment of the oral CHK1 inhibitor, SRA737, and low-dose gemcitabine enhances the effect of programmed death ligand 1 blockade by modulating the immune microenvironment in SCLC. J Thorac Oncol, 2019, 14: 2152–2163

    Article  CAS  Google Scholar 

  149. Riesterer O, Matsumoto F, Wang L, et al. A novel Chk inhibitor, XL-844, increases human cancer cell radiosensitivity through promotion of mitotic catastrophe. Invest New Drugs, 2011, 29: 514–522

    Article  CAS  Google Scholar 

  150. Reithofer MR, Valiahdi SM, Galanski M, et al. Novel endothall-containing platinum(IV) complexes: Synthesis, characterization, and cytotoxic activity. Chem Biodiversity, 2008, 5: 2160–2170

    Article  CAS  Google Scholar 

  151. Yu CW, Li KKW, Pang SK, et al. Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane. Bioorg Med Chem Lett, 2006, 16: 1686–1691

    Article  CAS  Google Scholar 

  152. Wang E, Xiong H, Zhou D, et al. Co-delivery of oxaliplatin and demethylcantharidin via a polymer-drug conjugate. Macromol Biosci, 2014, 14: 588–596

    Article  CAS  Google Scholar 

  153. Zhou D, Xiao H, Meng F, et al. A polymer-(tandem drugs) conjugate for enhanced cancer treatment. Adv Healthcare Mater, 2013, 2: 822–827

    Article  CAS  Google Scholar 

  154. Fan Z, Luo H, Zhou J, et al. Checkpoint kinase 1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair. Oncol Rep, 2020, 44: 2152–2164

    CAS  Google Scholar 

  155. Sanij E, Hannan K, Xuan J, et al. Inhibition of RNA polymerase I transcription activates targeted DNA damage response and enhances the efficacy of PARP inhibitors in high-grade serous ovarian cancer. Clin Cancer Res, 2020, 26: 74–75

    Article  Google Scholar 

  156. Tang Xu, Gou X. Is chemotherapy the only option to treat the residual solid tumor cells at the G0 phase after inducing them into the cell cycle? Negative, 2019, 10: 26–28

    Google Scholar 

  157. Milanovic M, Fan DNY, Belenki D, et al. Senescence-associated reprogramming promotes cancer stemness. Nature, 2018, 553: 96–100

    Article  CAS  Google Scholar 

  158. Lee JH, Koung FP, Cho CK, et al. Review of tumor dormancy therapy using traditional oriental herbal medicine. J Pharmacopuncture, 2013, 16: 12–20

    Article  Google Scholar 

  159. Nam J, Son S, Park KS, et al. Cancer nanomedicine for combination cancer immunotherapy. Nat Rev Mater, 2019, 4: 398–414

    Article  Google Scholar 

  160. Dai T, Ye F, Hu P, et al. A strategy for enhanced tumor targeting of photodynamic therapy based on Escherichia coli-driven drug delivery system. Sci China Mater, 2021, 64: 232–240

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (51703105, 21675091, and 21874078), Taishan Young Scholar Program of Shandong Province (tsqn20161027), the Natural Science Foundation of Shandong Province (ZR2017BEM012), the Major Science and Technology Innovation Project of Shandong Province (2018CXGC1407), the Key Research and Development Project of Shandong Province (2016GGX102028, 2016GGX102039, and 2017GGX20111), China Postdoctoral Science Foundation (2018M630752), the Postdoctoral Scientific Research Foundation of Qingdao, and the First Class Discipline Project of Shandong Province (22074072).

Author information

Authors and Affiliations

Authors

Contributions

Author contributions Sun Y and Hu H wrote the original draft; Jing X, Meng Q and Yu B provided some meaningful suggestions for the draft writing; Hu H and Shen Y reviewed and revised the manuscript; Cong H supervised this study.

Corresponding author

Correspondence to Hailin Cong  (丛海林).

Ethics declarations

Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Ying Sun received her BA degree in polymer material and engineering from Qingdao University in 2019. She is pursuing her MSc degree in materials science in Prof. Cong’s laboratory. Her research focuses on the combination of cell cycle regulation and chemotherapy.

Hao Hu received his PhD degree from Beijing University of Chemical Technology in 2016 with Prof. Fujian Xu. In 2016, he joined the College of Materials Science and Engineering at Qingdao University as a Lecturer. His research focuses on developing smart gene/drug delivery systems for cancer therapy.

Hailin Cong received his PhD degree from Peking University in 2004 with Prof. Weixiao Cao. After completing a Postdoctoral Fellowship at the University of California, Davis, he joined Qingdao University in 2009 as a Distinguished Professor and Distinguished Young Scientist of Shandong Province. His current research interests lie in the synthesis and application of advanced micro-nano materials. He received The Natural Science Award from the Ministry of Education of China (2007). He has served as Member of Editorial Board of Nanoscience & Nanotechnology since 2008, Vice Chair of Editorial Committee of China International Nanoscience and Technology Symposium since 2009, and Member of Editorial Board of Integrated Ferroelectrics since 2012.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Y., Hu, H., Jing, X. et al. Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy. Sci. China Mater. 64, 1827–1848 (2021). https://doi.org/10.1007/s40843-020-1627-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40843-020-1627-4

Keywords

Navigation