Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Its poor response to current treatment options in advanced stages and the need for efficient diagnosis in early stages call for the development of new therapeutic and diagnostic strategies. Some of them are based on the use of nanometric materials as carriers and releasers of therapeutic agents and fluorescent molecules, or even on the utilization of magnetic materials that provide very interesting properties. These nanoformulations present several advantages compared with the free molecular cargo, including increased drug solubility, bioavailability, stability, and tumor specificity. Moreover, tumor multidrug resistance has been decreased in some cases, leading to improved treatment effectiveness by reducing drug dose and potential side effects. Here, we present an updated overview of the latest advances in clinical research, in vivo studies, and patents regarding the application of nanoformulations in the treatment of CRC. Based on the information gathered, a wide variety of nanomaterials are being investigated in clinical research, even in advanced phases, i.e., close to reaching the market. In sum, these novel materials can offer remarkable advantages with respect to current therapies, which could be complemented or even replaced by these nanosystems in the near future.

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Abbreviations

5-FU:

5-Fluorouracil

FOLFIRI:

5-FU/LV/IRI

FOLFIRINOX:

5-FU/LV/IRI/OXA

FOLFOX:

5-FU/LV/OXA

HCPT:

10-Hydroxycamptothecin

Apt:

Aptamer

AD:

Arginine deiminase

BC:

Breast cancer

BCRP:

Breast cancer resistance protein

CAP:

Capecitabine

CRT:

Chemoradiotherapy

CRC:

Colorectal cancer

TPGS:

d-α-Tocopherol polyethylene glycol 1000 succinate

DPD:

Dihydropyrimidine dehydrogenase

DOX:

Doxorubicin

EGFR:

Epidermal growth factor receptor

EpCAM:

Epithelial cell adhesion molecule

FUPEP:

FOLFIRI and PEP02

GR:

Glutathione reductase

HNM:

Head and neck melanoma

HT:

Hyperthermia

IRI:

Irinotecan

LV or FOL:

Leucovorin or folinic acid

LC:

Lung cancer

MDR:

Multidrug resistance

NPs:

Nanoparticles

OXA:

Oxaliplatin

PGP:

P-glycoprotein

PEDF:

Pigment epithelium-derived factor

PEG:

Poly (ethylene glycol)

PEI:

Polyetherimide

C225-PCQD:

Porphyrin carbon quantum dots conjugated with cetuximab

PTT:

Photothermal therapy

anti-PDL1:

Programmed cell death-1 ligand-1 antibody

PCFT:

Proton-coupled folate transporter

RT:

Radiotherapy

RFC-1:

Reduced folate transporter 1

shRNA:

Short hairpin RNA molecule

SECs:

Sinusoidal endothelial cells

SPIONs:

Superparamagnetic iron oxide nanoparticles

TS:

Thymidylate synthase

Tfr:

Transferrin

TPP:

Triphenylphosphonium

TDP1:

Tyrosyl-DNA phosphodiesterase 1

UGT:

UDP-glucuronosyltransferases

VEGFR:

Vascular endothelial growth factor receptor

References

  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. https://doi.org/10.3322/caac.21442.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    The Lancet null. GLOBOCAN 2018: counting the toll of cancer. Lancet Lond Engl. 2018;392:985. https://doi.org/10.1016/S0140-6736(18)32252-9.

  3. 3.

    Kotelevets L, Chastre E, Desmaële D, Couvreur P. Nanotechnologies for the treatment of colon cancer: from old drugs to new hope. Int J Pharm. 2016;514:24–40. https://doi.org/10.1016/j.ijpharm.2016.06.005.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. Colorectal cancer. Nat Rev Dis Primer. 2015;1:15065. https://doi.org/10.1038/nrdp.2015.65.

    Article  Google Scholar 

  5. 5.

    Bevan R, Rutter MD. Colorectal cancer screening-who, how, and when? Clin Endosc. 2018;51:37–49. https://doi.org/10.5946/ce.2017.141.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394:1467–80. https://doi.org/10.1016/S0140-6736(19)32319-0.

    Article  PubMed  Google Scholar 

  7. 7.

    Yiu AJ, Yiu CY. Biomarkers in colorectal cancer. Anticancer Res. 2016;36:1093–102.

    CAS  PubMed  Google Scholar 

  8. 8.

    Tauriello DVF, Calon A, Lonardo E, Batlle E. Determinants of metastatic competency in colorectal cancer. Mol Oncol. 2017;11:97–119. https://doi.org/10.1002/1878-0261.12018.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Welt S, Ritter G, Williams C, Cohen LS, John M, Jungbluth A, et al. Phase I study of anticolon cancer humanized antibody A33. Clin Cancer Res. 2003;9:1338–46.

    CAS  PubMed  Google Scholar 

  10. 10.

    Kilari D, Guancial E, Kim ES. Role of copper transporters in platinum resistance. World J Clin Oncol. 2016;7:106–13. https://doi.org/10.5306/wjco.v7.i1.106.

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Fernández Montes A, Martínez Lago N, Covela Rúa M, de la Cámara GJ, González Villaroel P, Méndez Méndez JC, et al. Efficacy and safety of FOLFIRI/aflibercept in second-line treatment of metastatic colorectal cancer in a real-world population: prognostic and predictive markers. Cancer Med. 2019;8:882–9. https://doi.org/10.1002/cam4.1903.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Seeber A, Gastl G. Targeted therapy of colorectal cancer. Oncol Res Treat. 2016;39:796–802.

    CAS  Article  Google Scholar 

  13. 13.

    Peeters M, Cervantes A, Moreno Vera S, Taieb J. Trifluridine/tipiracil: an emerging strategy for the management of gastrointestinal cancers. Future Oncol Lond Engl. 2018;14:1629–45. https://doi.org/10.2217/fon-2018-0147.

    CAS  Article  Google Scholar 

  14. 14.

    Wu SY, Huang YJ, Tzeng YM, Huang CYF, Hsiao M, Wu ATH, et al. Destruxin B suppresses drug-resistant colon tumorigenesis and stemness is associated with the upregulation of mir-214 and downregulation of mTOR/β-catenin pathway. Cancers. 2018;10. https://doi.org/10.3390/cancers10100353.

  15. 15.

    Zhang N, Yin Y, Xu SJ, Chen WS. 5-Fluorouracil: mechanisms of resistance and reversal strategies. Mol Basel Switz. 2008;13:1551–69.

    CAS  Google Scholar 

  16. 16.

    DeNardo GL, DeNardo SJ. Concepts, consequences, and implications of theranosis. Semin Nucl Med. 2012;42:147–50. https://doi.org/10.1053/j.semnuclmed.2011.12.003.

    Article  PubMed  Google Scholar 

  17. 17.

    Alibolandi M, Hoseini F, Mohammadi M, Ramezani P, Einafshar E, Taghdisi SM, et al. Curcumin-entrapped MUC-1 aptamer targeted dendrimer-gold hybrid nanostructure as a theranostic system for colon adenocarcinoma. Int J Pharm. 2018;549:67–75. https://doi.org/10.1016/j.ijpharm.2018.07.052.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Odin E, Sondén A, Gustavsson B, Carlsson G, Wettergren Y. Expression of folate pathway genes in stage III colorectal cancer correlates with recurrence status following adjuvant bolus 5-FU-based chemotherapy. Mol Med Camb Mass. 2015;21:597–604. https://doi.org/10.2119/molmed.2014.00192.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Jensen NF, Stenvang J, Beck MK, Hanáková B, Belling KC, Do KN, et al. Establishment and characterization of models of chemotherapy resistance in colorectal cancer: towards a predictive signature of chemoresistance. Mol Oncol. 2015;9:1169–85. https://doi.org/10.1016/j.molonc.2015.02.008.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Dienstmann R, Salazar R, Tabernero J. Overcoming resistance to anti-EGFR therapy in colorectal cancer. Am Soc Clin Oncol Educ Book. 2015;e149–156. https://doi.org/10.14694/EdBook_AM.2015.35.e149.

  21. 21.

    Morris SA, Farrell D, Grodzinski P. Nanotechnologies in cancer treatment and diagnosis. J Natl Compr Cancer Netw JNCCN. 2014;12:1727–33.

    CAS  Article  Google Scholar 

  22. 22.

    Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17:20–37. https://doi.org/10.1038/nrc.2016.108.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Swain S, Sahu PK, Beg S, Babu SM. Nanoparticles for cancer targeting: current and future directions. Curr Drug Deliv. 2016;13:1290–302.

    CAS  Article  Google Scholar 

  24. 24.

    Lai P, Daear W, Löbenberg R, Prenner EJ. Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly(d,l-lactide-co-glycolic acid) and polyalkylcyanoacrylate. Colloids Surf B Biointerfaces. 2014;118:154–63. https://doi.org/10.1016/j.colsurfb.2014.03.017.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Kamaly N, Yameen B, Wu J, Farokhzad OC. Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev. 2016;116:2602–63. https://doi.org/10.1021/acs.chemrev.5b00346.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Maeda H. Polymer therapeutics and the EPR effect. J Drug Target. 2017;25:781–5. https://doi.org/10.1080/1061186X.2017.1365878.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Banerjee A, Pathak S, Subramanium VD, G D, Murugesan R, Verma RS. Strategies for targeted drug delivery in treatment of colon cancer: current trends and future perspectives. Drug Discov Today. 2017;22:1224–32. https://doi.org/10.1016/j.drudis.2017.05.006.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Yue X, Dai Z. Liposomal nanotechnology for cancer theranostics. Curr Med Chem. 2018;25:1397–408. https://doi.org/10.2174/0929867324666170306105350.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Zeng WJ, Peng CW, Yuan JP, Cui R, Li Y. Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification. Int J Nanomedicine. 2015;10:1759–68. https://doi.org/10.2147/IJN.S70228.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Babu LT, Paira P. Current application of quantum dots (QD) in cancer therapy: a review. Mini Rev Med Chem. 2017;17:1406–15. https://doi.org/10.2174/1389557517666170315125504.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Viswanath B, Kim S, Lee K. Recent insights into nanotechnology development for detection and treatment of colorectal cancer. Int J Nanomedicine. 2016;11:2491–504. https://doi.org/10.2147/IJN.S108715.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Croy SR, Kwon GS. Polymeric micelles for drug delivery. Curr Pharm Des. 2006;12:4669–84.

    CAS  Article  Google Scholar 

  33. 33.

    Kesharwani SS, Kaur S, Tummala H, Sangamwar AT. Overcoming multiple drug resistance in cancer using polymeric micelles. Expert Opin Drug Deliv. 2018;15:1127–42. https://doi.org/10.1080/17425247.2018.1537261.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Mignani S, Rodrigues J, Tomas H, Zablocka M, Shi X, Caminade AM, et al. Dendrimers in combination with natural products and analogues as anti-cancer agents. Chem Soc Rev. 2018;47:514–32. https://doi.org/10.1039/c7cs00550d.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99. https://doi.org/10.2147/IJN.S68861.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Euliss LE, DuPont JA, Gratton S, DeSimone J. Imparting size, shape, and composition control of materials for nanomedicine. Chem Soc Rev. 2006;35:1095–104.

    CAS  Article  Google Scholar 

  37. 37.

    Naeem M, Awan UA, Subhan F, Cao J, Hlaing SP, Lee J, et al. Advances in colon-targeted nano-drug delivery systems: challenges and solutions. Arch Pharm Res. 2020;43:153–69. https://doi.org/10.1007/s12272-020-01219-0.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Nakamura H, Fang J, Jun F, Maeda H. Development of next-generation macromolecular drugs based on the EPR effect: challenges and pitfalls. Expert Opin Drug Deliv. 2015;12:53–64. https://doi.org/10.1517/17425247.2014.955011.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Casadó A, Sagristá ML, Mora M. Formulation and in vitro characterization of thermosensitive liposomes for the delivery of irinotecan. J Pharm Sci. 2014;103:3127–38. https://doi.org/10.1002/jps.24097.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Feng ST, Li J, Luo Y, Yin T, Cai H, Wang Y, et al. pH-sensitive nanomicelles for controlled and efficient drug delivery to human colorectal carcinoma LoVo cells. PLoS One. 2014;9:e100732. https://doi.org/10.1371/journal.pone.0100732.

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Akbarzadeh A, Rezaei-Sadabady R, Davaran S, Joo SW, Zarghami N, Hanifehpour Y, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8:102. https://doi.org/10.1186/1556-276X-8-102.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Pan ZZ, Wang HY, Zhang M, Lin TT, Zhang WY, Zhao PF, et al. Nuclear-targeting TAT-PEG-Asp8-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer. Acta Pharmacol Sin. 2016;37:1110–20. https://doi.org/10.1038/aps.2016.48.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Jiang Y, Guo Z, Fang J, Wang B, Lin Z, Chen ZS, et al. A multi-functionalized nanocomposite constructed by gold nanorod core with triple-layer coating to combat multidrug resistant colorectal cancer. Mater Sci Eng C Mater Biol Appl. 2020;107:110224. https://doi.org/10.1016/j.msec.2019.110224.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Wang B, Wu S, Lin Z, Jiang Y, Chen Y, Chen ZS, et al. A personalized and long-acting local therapeutic platform combining photothermal therapy and chemotherapy for the treatment of multidrug-resistant colon tumor. Int J Nanomedicine. 2018;13:8411–27. https://doi.org/10.2147/IJN.S184728.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Negi LM, Jaggi M, Joshi V, Ronodip K, Talegaonkar S. Hyaluronan coated liposomes as the intravenous platform for delivery of imatinib mesylate in MDR colon cancer. Int J Biol Macromol. 2015;73:222–35. https://doi.org/10.1016/j.ijbiomac.2014.11.026.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Juang V, Chang CH, Wang CS, Wang HE, Lo YL. pH-responsive PEG-shedding and targeting peptide-modified nanoparticles for dual-delivery of irinotecan and microRNA to enhance tumor-specific therapy. Small Weinh Bergstr Ger. 2019;15(e1903296). https://doi.org/10.1002/smll.201903296.

  47. 47.

    Shao M, Chang C, Liu Z, Chen K, Zhou Y, Zheng G, et al. Polydopamine coated hollow mesoporous silica nanoparticles as pH-sensitive nanocarriers for overcoming multidrug resistance. Colloids Surf B Biointerfaces. 2019;183:110427. https://doi.org/10.1016/j.colsurfb.2019.110427.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Zhang X, Zhao M, Cao N, Qin W, Zhao M, Wu J, et al. Construction of a tumor microenvironment pH-responsive cleavable PEGylated hyaluronic acid nano-drug delivery system for colorectal cancer treatment. Biomater Sci. 2020;8:1885–96. https://doi.org/10.1039/c9bm01927h.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Wei Y, Gu X, Sun Y, Meng F, Storm G, Zhong Z. Transferrin-binding peptide functionalized polymersomes mediate targeted doxorubicin delivery to colorectal cancer in vivo. J Control Release Off J Control Release Soc. 2020;319:407–15. https://doi.org/10.1016/j.jconrel.2020.01.012.

    CAS  Article  Google Scholar 

  50. 50.

    Shi H, Liang GF, Li Y, Li JH, Jing AH, Feng WP, et al. Preparation and evaluation of upconversion nanoparticles based miRNA delivery carrier in colon cancer mice model. J Biomed Nanotechnol. 2019;15:2240–50. https://doi.org/10.1166/jbn.2019.2840.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Zhong Y, Su T, Shi Q, Feng Y, Tao Z, Huang Q, et al. Co-administration of iRGD enhances tumor-targeted delivery and anti-tumor effects of paclitaxel-loaded PLGA nanoparticles for colorectal cancer treatment. Int J Nanomedicine. 2019;14:8543–60. https://doi.org/10.2147/IJN.S219820.

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Le Goas M, Paquet M, Paquirissamy A, Guglielmi J, Compin C, Thariat J, et al. Improving 131I radioiodine therapy by hybrid polymer-grafted gold nanoparticles. Int J Nanomedicine. 2019;14:7933–46. https://doi.org/10.2147/IJN.S211496.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Zhao Y, Xu J, Le VM, Gong Q, Li S, Gao F, et al. EpCAM Aptamer-functionalized cationic liposome-based nanoparticles loaded with miR-139-5p for targeted therapy in colorectal cancer. Mol Pharm. 2019;16:4696–710. https://doi.org/10.1021/acs.molpharmaceut.9b00867.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Zhong Y, Ma Z, Wang F, Wang X, Yang Y, Liu Y, et al. In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles. Nat Biotechnol. 2019;37:1322–31. https://doi.org/10.1038/s41587-019-0262-4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Simón M, Norregaard K, Jørgensen JT, Oddershede LB, Kjaer A. Fractionated photothermal therapy in a murine tumor model: comparison with single dose. Int J Nanomedicine. 2019;14:5369–79. https://doi.org/10.2147/IJN.S205409.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Chen Y, Li N, Xu B, Wu M, Yan X, Zhong L, et al. Polymer-based nanoparticles for chemo/gene-therapy: evaluation its therapeutic efficacy and toxicity against colorectal carcinoma. Biomed Pharmacother Biomedecine Pharmacother. 2019;118:109257. https://doi.org/10.1016/j.biopha.2019.109257.

    CAS  Article  Google Scholar 

  57. 57.

    Tsakiris N, Papavasileiou M, Bozzato E, Lopes A, Vigneron AM, Préat V. Combinational drug-loaded lipid nanocapsules for the treatment of cancer. Int J Pharm. 2019;569:118588. https://doi.org/10.1016/j.ijpharm.2019.118588.

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Xing J, Zhang X, Wang Z, Zhang H, Chen P, Zhou G, et al. Novel lipophilic SN38 prodrug forming stable liposomes for colorectal carcinoma therapy. Int J Nanomedicine. 2019;14:5201–13. https://doi.org/10.2147/IJN.S204965.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Li C, Cai G, Song D, Gao R, Teng P, Zhou L, et al. Development of EGFR-targeted evodiamine nanoparticles for the treatment of colorectal cancer. Biomater Sci. 2019;7:3627–39. https://doi.org/10.1039/c9bm00613c.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Rosch JG, Landry MR, Thomas CR, Sun C. Enhancing chemoradiation of colorectal cancer through targeted delivery of raltitrexed by hyaluronic acid coated nanoparticles. Nanoscale. 2019;11:13947–60. https://doi.org/10.1039/c9nr04320a.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Cheng G, Zhang X, Chen Y, Lee RJ, Wang J, Yao J, et al. Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer. Colloids Surf B Biointerfaces. 2019;181:822–9. https://doi.org/10.1016/j.colsurfb.2019.06.020.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Zhang X, Men K, Zhang Y, Zhang R, Yang L, Duan X. Local and systemic delivery of mRNA encoding survivin-T34A by lipoplex for efficient colon cancer gene therapy. Int J Nanomedicine. 2019;14:2733–51. https://doi.org/10.2147/IJN.S198747.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Xu M, Wen Y, Liu Y, Tan X, Chen X, Zhu X, et al. Hollow mesoporous ruthenium nanoparticles conjugated bispecific antibody for targeted anti-colorectal cancer response of combination therapy. Nanoscale. 2019;11:9661–78. https://doi.org/10.1039/c9nr01904a.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Jain A, Jain R, Jain S, Khatik R, Veer KD. Minicapsules encapsulating nanoparticles for targeting, apoptosis induction and treatment of colon cancer. Artif Cells Nanomedicine Biotechnol. 2019;47:1085–93. https://doi.org/10.1080/21691401.2019.1593848.

    CAS  Article  Google Scholar 

  65. 65.

    Li HQ, Ye W-L, Huan ML, Cheng Y, Liu DZ, Cui H, et al. Mitochondria and nucleus delivery of active form of 10-hydroxycamptothecin with dual shell to precisely treat colorectal cancer. Nanomed. 2019;14:1011–32. https://doi.org/10.2217/nnm-2018-0227.

    CAS  Article  Google Scholar 

  66. 66.

    Gu X, Wei Y, Fan Q, Sun H, Cheng R, Zhong Z, et al. cRGD-decorated biodegradable polytyrosine nanoparticles for robust encapsulation and targeted delivery of doxorubicin to colorectal cancer in vivo. J Control Release. 2019;301:110–8. https://doi.org/10.1016/j.jconrel.2019.03.005.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Zhao C, Cao W, Zheng H, Xiao Z, Hu J, Yang L, et al. Acid-responsive nanoparticles as a novel oxidative stress-inducing anticancer therapeutic agent for colon cancer. Int J Nanomedicine. 2019;14:1597–618. https://doi.org/10.2147/IJN.S189923.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Abed Z, Beik J, Laurent S, Eslahi N, Khani T, Davani ES, et al. Iron oxide-gold core-shell nano-theranostic for magnetically targeted photothermal therapy under magnetic resonance imaging guidance. J Cancer Res Clin Oncol. 2019;145:1213–9. https://doi.org/10.1007/s00432-019-02870-x.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Qiu R, Qian F, Wang X, Li H, Wang L. Targeted delivery of 20(S)-ginsenoside Rg3-based polypeptide nanoparticles to treat colon cancer. Biomed Microdevices. 2019;21:18. https://doi.org/10.1007/s10544-019-0374-0.

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Mulens-Arias V, Nicolás-Boluda A, Gehanno A, Balfourier A, Carn F, Gazeau F. Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocomposites as a photothermal theranostic agent. Nanoscale. 2019;11:3344–59. https://doi.org/10.1039/c8nr09849b.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Ren Y, Li X, Han B, Zhao N, Mu M, Wang C, et al. Improved anti-colorectal carcinomatosis effect of tannic acid co-loaded with oxaliplatin in nanoparticles encapsulated in thermosensitive hydrogel. Eur J Pharm Sci. 2019;128:279–89. https://doi.org/10.1016/j.ejps.2018.12.007.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Xie K, Song S, Zhou L, Wan J, Qiao Y, Wang M, et al. Revival of a potent therapeutic maytansinoid agent using a strategy that combines covalent drug conjugation with sequential nanoparticle assembly. Int J Pharm. 2019;556:159–71. https://doi.org/10.1016/j.ijpharm.2018.12.017.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Sesarman A, Tefas L, Sylvester B, Licarete E, Rauca V, Luput L, et al. Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment. Drug Deliv Transl Res. 2019;9:260–72. https://doi.org/10.1007/s13346-018-00598-8.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Thébault CJ, Ramniceanu G, Michel A, Beauvineau C, Girard C, Seguin J, et al. In vivo evaluation of magnetic targeting in mice colon tumors with ultra-magnetic liposomes monitored by MRI. Mol Imaging Biol. 2019;21:269–78. https://doi.org/10.1007/s11307-018-1238-3.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Näkki S, Wang JTW, Wu J, Fan L, Rantanen J, Nissinen T, et al. Designed inorganic porous nanovector with controlled release and MRI features for safe administration of doxorubicin. Int J Pharm. 2019;554:327–36. https://doi.org/10.1016/j.ijpharm.2018.10.074.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Afsharzadeh M, Abnous K, Yazdian-Robati R, Ataranzadeh A, Ramezani M, Hashemi M. Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA-PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo. J Cell Physiol mayo de. 2019;234:6099–107.

    CAS  Article  Google Scholar 

  77. 77.

    Hao M, Kong C, Jiang C, Hou R, Zhao X, Li J, et al. Polydopamine-coated Au-Ag nanoparticle-guided photothermal colorectal cancer therapy through multiple cell death pathways. Acta Biomater. 2019;83:414–24. https://doi.org/10.1016/j.actbio.2018.10.032.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20. https://doi.org/10.1056/NEJMoa1500596.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68. https://doi.org/10.1056/NEJMra1703481.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Luo L, Yang J, Zhu C, Jiang M, Guo X, Li W, et al. Sustained release of anti-PD-1 peptide for perdurable immunotherapy together with photothermal ablation against primary and distant tumors. J Control Release. 2018;278:87–99. https://doi.org/10.1016/j.jconrel.2018.04.002.

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Song W, Shen L, Wang Y, Liu Q, Goodwin TJ, Li J, et al. Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap. 2018;9:2237. https://doi.org/10.1038/s41467-018-04605-x.

  82. 82.

    Ni Q, Zhang F, Liu Y, Wang Z, Yu G, Liang B, et al. A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer. 2020;6:eaaw6071. https://doi.org/10.1126/sciadv.aaw6071.

  83. 83.

    Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater. 2017;16:489–96. https://doi.org/10.1038/nmat4822.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Luo M, Wang H, Wang Z, Cai H, Lu Z, Li Y, et al. A STING-activating nanovaccine for cancer immunotherapy. Nat Nanotechnol. 2017;12:648–54. https://doi.org/10.1038/nnano.2017.52.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Alabi C, Vegas A, Anderson D. Attacking the genome: emerging siRNA nanocarriers from concept to clinic. Curr Opin Pharmacol. 2012;12:427–33. https://doi.org/10.1016/j.coph.2012.05.004.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66. https://doi.org/10.1038/nrc2602.

    CAS  Article  PubMed  Google Scholar 

  87. 87.

    Tian X, Nguyen M, Foote HP, Caster JM, Roche KC, Peters CG, et al. CRLX101, a nanoparticle-drug conjugate containing camptothecin, improves rectal cancer chemoradiotherapy by inhibiting DNA repair and HIF1α. Cancer Res. 2017;77:112–22. https://doi.org/10.1158/0008-5472.CAN-15-2951.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Chibaudel B, Maindrault-Gœbel F, Bachet J-B, Louvet C, Khalil A, Dupuis O, et al. PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM-398) or irinotecan with leucovorin/5-fluorouracil as second-line therapy in metastatic colorectal cancer. Cancer Med. 2016;5:676–83. https://doi.org/10.1002/cam4.635.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Lyon PC, Griffiths LF, Lee J, Chung D, Carlisle R, Wu F, et al. Clinical trial protocol for TARDOX: a phase I study to investigate the feasibility of targeted release of lyso-thermosensitive liposomal doxorubicin (ThermoDox®) using focused ultrasound in patients with liver tumours. J Ther Ultrasound. 2017;5:28. https://doi.org/10.1186/s40349-017-0104-0.

    Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Golan T, Grenader T, Ohana P, Amitay Y, Shmeeda H, La-Beck NM, et al. Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients. Cancer Med. 2015;4:1472–83. https://doi.org/10.1002/cam4.491.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Maitra R, Halpin PA, Karlson KH, Page RL, Paik DY, Leavitt MO, et al. Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression. Biochem J. 2001;355:617–24.

    CAS  Article  Google Scholar 

  92. 92.

    Norris RE, Shusterman S, Gore L, Muscal JA, Macy ME, Fox E, et al. Phase 1 evaluation of EZN-2208, a polyethylene glycol conjugate of SN38, in children adolescents and young adults with relapsed or refractory solid tumors. Pediatr Blood Cancer. 2014;61:1792–7. https://doi.org/10.1002/pbc.25105.

    CAS  Article  PubMed  Google Scholar 

  93. 93.

    Garrett CR, Bekaii-Saab TS, Ryan T, Fisher GA, Clive S, Kavan P, et al. Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer. 2013;119(24):4223–30. https://doi.org/10.1002/cncr.28358.

    CAS  Article  PubMed  Google Scholar 

  94. 94.

    Abdellatif AAH, Zayed G, El-Bakry A, Zaky A, Saleem IY, Tawfeek HM. Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors. Drug Dev Ind Pharm. 2016;42:1782–91. https://doi.org/10.3109/03639045.2016.1173052.

    CAS  Article  PubMed  Google Scholar 

  95. 95.

    Tomlinson BK, Thomson JA, Bomalaski JS, Diaz M, Akande T, Mahaffey N, et al. Phase I trial of arginine deprivation therapy with ADI-PEG 20 plus docetaxel in patients with advanced malignant solid tumors. Clin Cancer Res. 2015;21:2480–6. https://doi.org/10.1158/1078-0432.CCR-14-2610.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Miyazaki K, Takaku H, Umeda M, Fujita T, Huang WD, Kimura T, et al. Potent growth inhibition of human tumor cells in culture by arginine deiminase purified from a culture medium of a Mycoplasma-infected cell line. Cancer Res. 1990;50:4522–7.

    CAS  PubMed  Google Scholar 

  97. 97.

    Ishida T, Huang CL, Wada H; Delta-Fly Pharma, Inc., Tokushima-shi (JP). Liposome containing shRNA molecule targeting a thymidylate synthase and use thereof. United States US2012301537A1. 2012.

  98. 98.

    Fitzgerald JB, Kearns JD, Lee H, Nering RC; Merrimack Pharmaceuticals Inc. Methods for treating cancer using combination therapies comprising an oligoclonal anti-egfr antibody preparation and liposomal irinotecan. World Intellectual Property Organization WO2017172678A1. 2017.

  99. 99.

    Zhu X, Wong Wk, Wu F; Hong Kong Baptist University, Hong Kong (HK). Conjugated porphyrin carbon quantum dots for targeted photodynamic therapy. United States US20180125976. 2018.

  100. 100.

    Dash AK, Trickler WJ; Creighton University, Omaha, NE (US). Mucoadhesive nanoparticles for cancer treatment. United States Patent US8242165B2. 2012.

  101. 101.

    Shieh DB, Yeh CS, Chen DH, Wu YN, Wu PC; National Cheng Kung University, Tainan (TW). Nano-carrier, complex of anticancer drug and nano-carrier, pharmaceutical composition thereof, method for manufacturing the complex, and method for treating cancer by using the pharmaceutical composition. United States Patent US8673358B2. 2014.

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Funding

This work was funded by the Consejería de Salud de la Junta de Andalucía (PI-0102-2017) and by the Group CTS-107. This work was also partially supported by a grant from the Instituto de Salud Carlos III (ISCIII) (PI19/01478) (FEDER).

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Cabeza, L., Perazzoli, G., Mesas, C. et al. Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents. AAPS PharmSciTech 21, 178 (2020). https://doi.org/10.1208/s12249-020-01731-y

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Key Words

  • colorectal cancer
  • nanoformulations
  • clinical trials
  • patents
  • in vivo studies