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Cancer nanomedicine: a review of recent success in drug delivery

Tran, Stephanie, DeGiovanni, Peter‐Joseph, Piel, Brandon, Rai, Prakash·2017·Clinical and Translational Medicine
DOI 10.1186/s40169-017-0175-0PMC PMC5725398
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Abstract

Cancer continues to be one of the most difficult global healthcare problems. Although there is a large library of drugs that can be used in cancer treatment, the problem is selectively killing all the cancer cells while reducing collateral toxicity to healthy cells. There are several biological barriers to effective drug delivery in cancer such as renal, hepatic, or immune clearance. Nanoparticles loaded with drugs can be designed to overcome these biological barriers to improve efficacy while reducing morbidity. Nanomedicine has ushered in a new era for drug delivery by improving the therapeutic indices of the active pharmaceutical ingredients engineered within nanoparticles. First generation nanomedicines have received widespread clinical approval over the past two decades, from Doxil ® (liposomal doxorubicin) in 1995 to Onivyde ® (liposomal irinotecan) in 2015. This review highlights the biological barriers to effective drug delivery in cancer, emphasizing the need for nanoparticles for improving therapeutic outcomes. A summary of different nanoparticles used for drug delivery applications in cancer are presented. The review summarizes recent successes in cancer nanomedicine in the clinic. The clinical trials of Onivyde leading to its approval in 2015 by the Food and Drug Adminstration are highlighted as a case study in the recent clinical success of nanomedicine against cancer. Next generation nanomedicines need to be better targeted to specifically destroy cancerous tissue, but face several obstacles in their clinical development, including identification of appropriate biomarkers to target, scale‐up of synthesis, and reproducible characterization. These hurdles need to be overcome through multidisciplinary collaborations across academia, pharmaceutical industry, and regulatory agencies in order to achieve the goal of eradicating cancer. This review discusses the current use of clinically approved nanomedicines, the investigation of nanomedicines in clinical trials, and the challenges that may hinder development of the nanomedicines for cancer treatment.

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Fig. 1 Overview of established nanomedicines in the clinic. This diagram shows an overview of the nanomedicines currently being investigated in the clinic for cancer treatment. Lipid-based, polymer-based, inorganic, viral, and drug-conjugated nanoparticles are examples of platforms that have been established in clinical research (Reproduced with permission from [3])
Fig. 1 Overview of established nanomedicines in the clinic. This diagram shows an overview of the nanomedicines currently being investigated in the clinic for cancer treatment. Lipid-based, polymer-based, inorganic, viral, and drug-conjugated nanoparticles are examples of platforms that have been established in clinical research (Reproduced with permission from [3])CC BY · PubMed Central
Fig. 2 Types of targeting for nanoparticle delivery to tumor tissue. a Passive targeting relies on the leaky vasculature that is exhibited by tumors, allowing nanoparticles to travel through the fenestrations and reach tumors. b Active targeting can be used when nanoparticles have ligands on their surface that can recognize and bind receptors that are overexpressed on tumor cells. c Triggered release allows nanoparticles to congregate if exposed to an external stimulus such as a magnetic field or light (Reproduced with permission from [3])
Fig. 2 Types of targeting for nanoparticle delivery to tumor tissue. a Passive targeting relies on the leaky vasculature that is exhibited by tumors, allowing nanoparticles to travel through the fenestrations and reach tumors. b Active targeting can be used when nanoparticles have ligands on their surface that can recognize and bind receptors that are overexpressed on tumor cells. c Triggered release allows nanoparticles to congregate if exposed to an external stimulus such as a magnetic field or light (Reproduced with permission from [3])CC BY · PubMed Central
Fig. 3 Organ systems that affect nanoparticle delivery. The method of entry affects circulation time, organ processing, and overall efficacy. Intravenously injected nanoparticles can extravasate from the bloodstream and enter organs such as the liver, spleen, bone marrow, and central nervous system. Nanomedicines that are administered orally can enter the gut and pass through the liver via the hepatic portal system. Inhaled nanomedicines may contact macrophages in pulmonary alveoli. Following circulation in organs, nanoparticles may encounter renal clearance in the kidneys (Reproduced with permission from [11])
Fig. 3 Organ systems that affect nanoparticle delivery. The method of entry affects circulation time, organ processing, and overall efficacy. Intravenously injected nanoparticles can extravasate from the bloodstream and enter organs such as the liver, spleen, bone marrow, and central nervous system. Nanomedicines that are administered orally can enter the gut and pass through the liver via the hepatic portal system. Inhaled nanomedicines may contact macrophages in pulmonary alveoli. Following circulation in organs, nanoparticles may encounter renal clearance in the kidneys (Reproduced with permission from [11])CC BY · PubMed Central
Fig. 4 A schematic illustrating replication fork arrest by a drug-aborted topoisomerase I-DNA cleavable complex. In this model, the camptothecin trapped topoisomerase I-DNA cleavable complex is viewed as a bulky DNA lesion which arrests the replication fork by blocking the movement of replication machinery. This blockage also alters the physical state of the cleavable complex and possibly leads to fork breakage at the complex site. At low levels of cleavable complexes, when only one replication fork is arrested, continued replication by the other unimpeded fork on the same plasmid DNA leads to the formation of linearized replication products. The irreversible replication arrest and fork breakage may be the cause of camptothecin’s S-phase-specific cytotoxicity [62, 63]
Fig. 4 A schematic illustrating replication fork arrest by a drug-aborted topoisomerase I-DNA cleavable complex. In this model, the camptothecin trapped topoisomerase I-DNA cleavable complex is viewed as a bulky DNA lesion which arrests the replication fork by blocking the movement of replication machinery. This blockage also alters the physical state of the cleavable complex and possibly leads to fork breakage at the complex site. At low levels of cleavable complexes, when only one replication fork is arrested, continued replication by the other unimpeded fork on the same plasmid DNA leads to the formation of linearized replication products. The irreversible replication arrest and fork breakage may be the cause of camptothecin’s S-phase-specific cytotoxicity [62, 63]CC BY · PubMed Central
Fig. 5 Metabolic pathway of irinotecan activation into SN-38 (Reproduced with permission from [81])
Fig. 5 Metabolic pathway of irinotecan activation into SN-38 (Reproduced with permission from [81])CC BY · PubMed Central
Fig. 6 Depiction of the exchange of triethylamine for irinotecan, which forms a stable complex with sucrose octasulfate inside the liposome (Reproduced with permission from [66])
Fig. 6 Depiction of the exchange of triethylamine for irinotecan, which forms a stable complex with sucrose octasulfate inside the liposome (Reproduced with permission from [66])CC BY · PubMed Central
Fig. 7 Kaplan–Meier curves of overall and progression-free survival. Abbreviations used are m for months, OS for overall survival, and PFS for progression-free survival (Reproduced with permission from [76])
Fig. 7 Kaplan–Meier curves of overall and progression-free survival. Abbreviations used are m for months, OS for overall survival, and PFS for progression-free survival (Reproduced with permission from [76])CC BY · PubMed Central
Fig. 8 The Kaplan–Meier estimates of overall and progression-free survival (a, b respectively) in the intent-to-treat population for liposomal irinotecan (PEP02), irinotecan, and docetaxal (Reproduced with permission from [69])
Fig. 8 The Kaplan–Meier estimates of overall and progression-free survival (a, b respectively) in the intent-to-treat population for liposomal irinotecan (PEP02), irinotecan, and docetaxal (Reproduced with permission from [69])CC BY · PubMed Central
Fig. 9 Kaplan–Meier survival analyses for phase III trial. HR hazard ratio. a Overall survival with nanoliposomal irinotecan plus fluorouracil and folinic acid versus fluorouracil and folinic acid. b Overall survival with nanoliposomal irinotecan monotherapy versus fluorouracil and folinic acid. c Progression-free survival with nanoliposomal irinotecan plus fluorouracil and folinic acid versus fluorouracil and folinic acid. d Progression-free survival with nanoliposomal irinotecan monotherapy versus fluorouracil and folinic acid (Reproduced with permission from [77])
Fig. 9 Kaplan–Meier survival analyses for phase III trial. HR hazard ratio. a Overall survival with nanoliposomal irinotecan plus fluorouracil and folinic acid versus fluorouracil and folinic acid. b Overall survival with nanoliposomal irinotecan monotherapy versus fluorouracil and folinic acid. c Progression-free survival with nanoliposomal irinotecan plus fluorouracil and folinic acid versus fluorouracil and folinic acid. d Progression-free survival with nanoliposomal irinotecan monotherapy versus fluorouracil and folinic acid (Reproduced with permission from [77])CC BY · PubMed Central

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Cites

Research works printed but not linked: 80

  1. 10.3322/caac.21395 · DOI
  2. 10.1016/j.jconrel.2014.12.030 · DOI
  3. 10.1158/1535-7163.MCT-06-0141 · DOI
  4. 10.1146/annurev-bioeng-071811-150124 · DOI
  5. 10.1016/j.nano.2015.08.006 · DOI
  6. 10.1517/17425247.2014.950564 · DOI · Paper page
  7. 10.1016/j.bpj.2010.06.016 · DOI
  8. Locatelli E, 2012, Biodegradable PLGA‐b‐PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system, J Nanopart Res, 14, 1, 10.1007/s11051-012-1316-4 · DOI
  9. 10.1016/j.jconrel.2012.01.043 · DOI
  10. 10.1016/j.tibtech.2016.07.006 · DOI · Paper page
  11. 10.1158/1078-0432.CCR-07-1441 · DOI
  12. 10.1021/mp100253e · DOI
  13. 10.1039/C6TB00847J · DOI
  14. 10.1002/cbf.1149 · DOI
  15. Chen K‐J, 2012, A thermoresponsive bubble‐generating liposomal system for triggering localized extracellular drug delivery, ACS Nano, 7, 438, 10.1021/nn304474j · DOI
  16. 10.1016/j.jconrel.2014.05.002 · DOI
  17. 10.1093/jnci/djm043 · DOI
  18. 10.1038/srep02953 · DOI
  19. 10.1016/j.jconrel.2004.11.023 · DOI
  20. Wang L, 2017, Multifunctional telodendrimer nanocarriers restore synergy of bortezomib and doxorubicin in ovarian cancer treatment, Can Res, 77, 3293, 10.1158/0008-5472.CAN-16-3119 · DOI
  21. 10.1021/nn3044066 · DOI
  22. 10.1021/acs.molpharmaceut.6b00388 · DOI
  23. Ahmed N, 2012, Theranostic applications of nanoparticles in cancer, Drug Discov Today, 17, 928, 10.1016/j.drudis.2012.03.010 · DOI
  24. 10.1016/j.addr.2010.09.002 · DOI
  25. 10.1002/smll.201303540 · DOI
  26. 10.1504/IJNM.2009.028116 · DOI
  27. 10.1126/science.1229568 · DOI
  28. 10.1088/0957-4484/22/11/115101 · DOI
  29. 10.2217/nnm.13.191 · DOI
  30. 10.1152/ajprenal.00290.2001 · DOI
  31. Liu J, 2013, Renal clearable inorganic nanoparticles: a new frontier of bionanotechnology, Mater Today, 16, 477, 10.1016/j.mattod.2013.11.003 · DOI
  32. 10.1073/pnas.0913667107 · DOI
  33. 10.1016/B978-0-12-391860-4.00006-9 · DOI
  34. 10.1602/neurorx.2.1.3 · DOI · Paper page
  35. 10.1016/j.ejpb.2008.08.021 · DOI · Paper page
  36. 10.1124/jpet.105.097139 · DOI · Paper page
  37. 10.1016/j.jconrel.2008.10.016 · DOI
  38. 10.1007/s00018-007-6390-x · DOI
  39. 10.1186/s12951-015-0075-7 · DOI
  40. 10.1080/10611860400015936 · DOI
  41. ShankerSharma H, 2012, Neurotoxicity of engineered nanoparticles from metals, CNS Neurol Disord Drug Targets, 11, 65, 10.2174/187152712799960817 · DOI
  42. 10.1016/j.toxlet.2012.08.009 · DOI
  43. 10.1021/nn400548g · DOI
  44. Alley SC, 2010, Antibody–drug conjugates: targeted drug delivery for cancer, Curr Opin Chem Biol, 14, 529, 10.1016/j.cbpa.2010.06.170 · DOI
  45. 10.1016/j.cbpa.2009.03.023 · DOI
  46. 10.1615/CritRevTherDrugCarrierSyst.v26.i6.10 · DOI
  47. 10.1126/science.364652 · DOI
  48. 10.1016/j.addr.2008.03.007 · DOI
  49. 10.1021/mp400190z · DOI
  50. 10.1016/j.polymer.2008.01.027 · DOI
  51. 10.1021/ja053962k · DOI
  52. 10.2147/IJN.S112660 · DOI
  53. 10.1126/science.275.5297.187 · DOI
  54. Almajhdi F, 2014, In‐vitro anticancer and antimicrobial activities of PLGA/silver nanofiber composites prepared by electrospinning, J Mater Sci, 25, 1045
  55. Elbaz NM, 2016, Core‐shell silver/polymeric nanoparticles‐based combinatorial therapy against breast cancer in‐vitro, Sci Rep, 6, 30729, 10.1038/srep30729 · DOI
  56. 10.1016/S0021-9258(17)38654-4 · DOI · Paper page
  57. Hsiang Y‐H, 1989, Arrest of replication forks by drugstabilized topoisomerase I‐DNA cleavable complexes as a mechanism of cell killing by camptothecin, Can Res, 49, 5077
  58. Zamboni WC, 2005, Relationship between plasma exposure of 9‐nitrocamptothecin and its 9‐aminocamptothecin metabolite and antitumor response in mice bearing human colon carcinoma xenografts, Clin Cancer Res, 11, 4867, 10.1158/1078-0432.CCR-05-0144 · DOI
  59. 10.2217/fon.15.333 · DOI
  60. 10.1158/0008-5472.CAN-05-4007 · DOI
  61. Chiang N‐J, 2016, A phase I dose‐escalation study of PEP02 (irinotecan liposome injection) in combination with 5‐fluorouracil and leucovorin in advanced solid tumors, BMC Cancer, 16, 907, 10.1186/s12885-016-2933-6 · DOI
  62. 10.1093/annonc/mdt002 · DOI
  63. Pan X, 2017, Construction of anti‐EGFR immunoliposomes via folate‐folate binding protein affinity, Int J Pharm, 336, 276, 10.1016/j.ijpharm.2006.12.007 · DOI
  64. 10.1038/bjc.2013.408 · DOI
  65. Stubbs M, 1994, Metabolic consequences of a reversed pH gradient in rat tumors, Cancer Res, 54, 4011
  66. 10.1038/nature07943 · DOI
  67. TinkleS McNeilSE MϋhlebachS BawaR BorchardG BarenholzYC TamarkinL DesaiN(2014)Nanomedicines: addressing the scientific and regulatory gap. Ann NY Acad Sci 1313:35–56 · DOI
  68. Ma MK, 2000, Pharmacokinetics of irinotecan and its metabolites SN‐38 and APC in children with recurrent solid tumors after protracted low‐dose irinotecan, Clin Cancer Res, 6, 813
  69. Cainelli F, 2009, Safety and efficacy of pegylated liposomal doxorubicin in HIV‐associated Kaposi’s sarcoma, Biologics, 3, 385
  70. Chen L, 2010, Phase I study of liposome irinotecan (PEP02) in combination with weekly infusion of 5‐FU/LV in advanced solid tumors, J Clin Oncol, 28, e13024, 10.1200/jco.2010.28.15_suppl.e13024 · DOI
  71. 10.1158/1078-0432.CCR-03-0655 · DOI · Paper page
  72. Ledet G, 2012, Nanomedicine: emerging therapeutics for the 21st century, US Pharm, 37, 7
  73. 10.1007/s00280-012-2042-4 · DOI
  74. Young C, 2011, CRLX101 (formerly IT‐101)—a novel nanopharmaceutical of camptothecin in clinical development, Current Bioactive Compd, 7, 8, 10.2174/157340711795163866 · DOI
  75. 10.1016/j.ijpharm.2006.12.007 · DOI
  76. Li C, 2014, Pegylated liposomal mitoxantrone is more therapeutically active than mitoxantrone in L1210 ascitic tumor and exhibits dose‐dependent activity saturation effect, Int J Pharm, 460, 165, 10.1016/j.ijpharm.2013.10.023 · DOI
  77. 10.1016/j.ejpb.2008.05.019 · DOI
  78. 10.1002/cncr.28974 · DOI · Paper page
  79. 10.1038/mt.2013.32 · DOI
  80. Young C, 2011, CRLX101 (formerly IT‐101) a novel nanopharmaceutical of camptothecin in clinical development, Curr Bioact Compd, 7, 8, 10.2174/157340711795163866 · DOI

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Metadata

Authors
Tran, S., DeGiovanni, P., Piel, B., & Rai, P.
Affiliations
  • Department of Biological Sciences University of Massachusetts 01854 Lowell MA USA
  • Department of Chemical Engineering University of Massachusetts 1 University ave 01854 Lowell MA USA
ORCID
Rai, Prakash
Venue
Clinical and Translational Medicine
Publisher
Wiley
Published
2017-12
Volume
6
Issue
1
ISSN
2001-1326
DOI
10.1186/s40169-017-0175-0
PMC
PMC5725398
Cited by
879
References
10
Language
en
Licence
Funders
  • National Cancer Institute (R00CA153948, K99CA153948)
  • National Institutes of Health (K99CA153948, R00CA153948)

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