Review Article

Nanotechnology in oncology: A concern on its unwanted

effects and ethics
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ABSTRACT
Nanotechnology is the new advent in science at present. The medical nanotechnology is present useful tool for the
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/29/2024

management of several diseases. For cancer, the application of nanotechnology can be seen, and it is approved
for the usefulness. On the other side of the coin, there are also unwanted effects of nanotechnology application in
oncology. In this article, the authors review and discuss on the possible unwanted adverse effects of nanotechnology
in oncology. The specific ethical concern for nanotechnology in oncology is also mentioned. Interesting quote from
leading ethicists and case studies are also presented in this short article.

Keywords: Adverse, cancer, ethics, nanotechnology, oncology

INTRODUCTION international organizations including to Food and Drug

Administration (FDA), Environmental Protection Agency, and
Nanotechnology is the new advent in science at present. Department of Agriculture and National Institutes of Health
The medical nanotechnology is present useful tool for the mentioned for the requirement for monitoring the adverse
management of several diseases. For cancer, the application effect of the merging nanotechnology.[5,6] The toxicology of
of nanotechnology can be seen, and it is approved for nanomaterials becomes an interesting issue in the present
the usefulness. The applied of the nanomaterials‑based day.
diagnostic, and therapeutic tool helps better cancer
management.[1] New nano‑based drug and target therapy are Indeed, there are many possible adverse effects of
the best examples of applied nanotechnology in oncology nanoparticle. The good example is the spermatoxicity[7] and
at present.[1‑3] On the other side of the coin, there are also hematotoxicity.[8,9] Although the nanotechnology is proposed
unwanted effects of nanotechnology application in oncology. for usefulness in reducing toxicity in cancer treatment,[10]
In this article, the authors review and discuss on the possible the risk from the toxicity directly related to the nanoparticle
unwanted adverse effects of nanotechnology in oncology. The should not be forgotten.
specific ethical concern for nanotechnology in oncology is
also mentioned. Interesting quote from leading ethicists and In addition, while the nanoparticle is widely used as tool
case studies is also presented in this short article. for cancer treatment at present, the great concern is on

P O S S I B L E U N WA N T E D A DV E R S E E F F E C T S O F Sora Yasri, Viroj Wiwanitkit1

NANOTECHNOLOGY IN ONCOLOGY KMT Primary Care Center, Bangkok, Thailand,
1
Department of Biological Science, Joseph Ayobabalola

The possible adverse effect of the nanotechnology University, Ilara‑Mokin, Nigeria

in oncology should be mentioned. The safety of the Address for correspondence: Dr. Sora Yasri,
nanotechnology has to checked. [4] At present, several KMT Primary Care Center, Bangkok, Thailand.
E‑mail: sorayari@outlook.co.th

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DOI:
How to cite this article: Yasri S, Wiwanitkit V. Nanotechnology in
10.4103/jms.jms_4_18 oncology: A concern on its unwanted effects and ethics. J Med Soc
2018;32:81-3.

© 2018 Journal of Medical Society | Published by Wolters Kluwer - Medknow 81

 Yasri and Wiwanitkit: Nanotechnology in oncology

the possible carcinogenicity of the nanoparticle. In fact, with moral and legal theory in light of these developments and
the genetic aberration due to exposure to nanomaterial is particularly since they represent the forefront of new medical
possible. This is already approved in the in vitro cell culture innovations.[23]”Hence, we need to follow the ethical guideline
in the report by Zhang et al.[11] Singh et al. noted that there in using new nanotechnology. The international collaboration
is a need to assess the genotoxicity of genotoxic potential of to deal with the ethical issue is interesting. A multidisciplinary
presently available nanomaterials.[12] Singh et al. noted that collaboration to create policies is required for help develop and
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several nanomaterials such as metal nanoparticles, metal implement of new sustainable nanotechnology.[24]
oxide nanoparticles, quantum dots, fullerenes, and fibrous
nanomaterials might cause nucleic acid abnormality and For the application of nanotechnology in oncology, ethical
this is the underlying mechanism of nanogenetoxicology.[12] issue is very important. The nanotechnology in oncology has
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Based on the fact that there is a possible genotoxicity effect, to be used in controlling diagnosis or treatment of cancer.
the next important question is on carcinogenesis process. For diagnosis, the special concern is on the privacy of the
The possible carcinogenesis of nanomaterials is little cancerous patient. For treatment, the use of nonlicenced
mentioned. The safety of the presently used nanomaterials new nanodrug or nanotreatment for management of the
has to be verified.[13] There are some interesting reports patients becomes a big ethical problem. Indeed, in nanotrials
on the carcinogenesis of nanomaterials indicating the in oncology, the patients usually get risk during exposure to
great risk of carcinogenesis.[14‑17] The good evidence of new nano‑object that is still unknown for its long‑term effect.
nanomaterial‑induced carcinogenesis is the very small The protection of patient’s right is I needed, but it is usually
nanoparticles that can enter into the human body through violated in real practice. In oncology, ones who participate
respiration. Shen et al. concluded that nanoparticles could be in any clinical trial have to get complete full nondisguised
uptaken by endocytosis process, and it can further directly or information. However, the nanotrial in oncology usually
indirectly cause damage to genes.[18] The mentioned damages contains myths. King stated that data on “risks of harm,
can interrupt the physiological course of cell cycle and result translational uncertainty, ambiguities in potential direct
in instability of the genome which might further induce benefit, and long‑term follow‑up” must be prepared and given
gene mutation or chromosome aberration and finally lead to all volunteer participants.[25] In judgment of a nanotrial
to cellular death or malignant transformation.[18] in oncology, the use of basic ethical principles “autonomy,
beneficence, nonmaleficence, justice” is required.[26] The good
Finally, there are already available nano‑based chemotherapy. example is the recent report on ethical evaluation on the
The adverse effect of those new drugs is still observable. study on “nanoparticle‑based therapy against brain tumors
Focusing on the pegylated liposomal doxorubicin (PLD) termed magnetic fluid hyperthermia.[26]”
namely Doxil®, the first FDA‑approved nano‑drug in 1995,
the adverse effect due to its doxorubicin can still be seen.[19] Disguising or incomplete data during trial of new nano‑drug
Ansari et al. reported that the most important side effect in oncology are considered unethical, and it is a direct
of PLD was dermatotoxicity although the observed adverse violation of the basic informed consent principle.[25,27,28]
dermatological side effects were not serious.[20] Gusella et al. The extension ethical concern of effect to the third party
reported an interesting observation regarding this new in external environment is also raised.[29] Jotterand and
nano‑based chemotherapeutic drug for relationship between Alexander noted that “We argue that our lack of data
age and exposure, decreased DNA repair ability, and increased concerning long‑term effects and risks of nanoparticles on
dermatotoxicity.[21] human health and the environment could undermine the
process when it comes to weighing the risks against the
ETHICAL CONCERN FOR NANOTECHNOLOGY IN ONCOLOGY: benefits.[30]” As noted by King,[25] the first‑in‑human research
A TOPIC THAT IS LITTLE MENTIONED on is usually an ethical challenge. King note that “Some
nanomedical technologies have additional characteristics
The ethical issue is an important concern for any new technology that should be addressed including: defining and describing
including to the new nanotechnology that should not forgotten. nanomedical interventions; bystander risks; the therapeutic
There are many important ideas from famous ethicists that will misconception; and a decision‑making context that includes
be further mentioned and quoted. Jameel noted that “Every both common uses of nanomaterials outside medicine and
technology also has a dual use, which needs to be understood persistent unknowns about the effects of nanosize.[25]”
and managed to extract maximum benefits for mankind and
the development of civilization.[22]” Naurato and Smith also In oncology, there are already some ethical case studies. The
mentioned that “professionals have had relatively little contact most famous case is on the “pazopanib.” Giving the reason

82 Journal of Medical Society / Volume 32 / Issue 2 / May-August 2018

 Yasri and Wiwanitkit: Nanotechnology in oncology

that “The Committee has come to the conclusion that author 10. Wang H, Yu J, Lu X, He X. Nanoparticle systems reduce systemic
toxicity in cancer treatment. Nanomedicine (Lond) 2016;11:103‑6.
Kadam has knowingly and intentionally falsified and/or
11. Zhang Q, Xu H, Zheng S, Su M, Wang J. Genotoxicity of mesoporous
fabricated results by manipulating LCMS/MS peak area data silica nanoparticles in human embryonic kidney 293 cells. Drug Test
to smooth kinetics and/or alter statistical significance. The Anal 2015;7:787‑96.
standard curve for the drug pazopanib was falsified to make 12. Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM,
Maffeis TG, et al. NanoGenotoxicology: The DNA damaging potential
it appear linear.” A report on the new nanodrug that can be
of engineered nanomaterials. Biomaterials 2009;30:3891‑914.
Downloaded from http://journals.lww.com/jmso by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AW

used for the management of sarcoma was retracted from 13. Tinkle SS. Nanotechnology: Collaborative opportunities for
publication in “J Control Release.” ecotoxicology and environmental health. Environ Toxicol Chem
2008;27:1823‑4.
14. Nagai H, Toyokuni S. Biopersistent fiber‑induced inflammation and
CONCLUSION
nYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/29/2024

carcinogenesis: Lessons learned from asbestos toward safety of fibrous

nanomaterials. Arch Biochem Biophys 2010;502:1‑7.
It can conclude that there are possible adverse effects 15. Nagai H, Toyokuni S. Differences and similarities between carbon
of nanotechnology that is widely used at present. While nanotubes and asbestos fibers during mesothelial carcinogenesis:
the nanomaterials are useful for cancer management, the Shedding light on fiber entry mechanism. Cancer Sci 2012;103:1378‑90.
16. Donaldson K, Poland CA. Inhaled nanoparticles and lung cancer – What
possibilities of toxicity and carcinogenicity exist. The control we can learn from conventional particle toxicology. Swiss Med Wkly
of the nanotechnology is needed and the basic nanoethics 2012;142:w13547.
principle has to be followed. 17. Grande F, Tucci P. Titanium dioxide nanoparticles: A risk for human
health? Mini Rev Med Chem 2016;16:762‑9.
18. Shen L, Wang Z, Zhou P. The genetic toxicity and toxicology
Financial support and sponsorship
mechanism of metal nano materials. Zhonghua Yu Fang Yi Xue Za Zhi
Nil. 2015;49:831‑4.
19. Barenholz Y. Doxil® – The first FDA‑approved nano‑drug: Lessons
Conflicts of interest learned. J Control Release 2012;160:117‑34.
20. Ansari L, Shiehzadeh F, Taherzadeh Z, Nikoofal‑Sahlabadi S,
There are no conflicts of interest.
Momtazi‑Borojeni AA, Sahebkar A, et al. The most prevalent side
effects of pegylated liposomal doxorubicin monotherapy in women with
REFERENCES metastatic breast cancer: A systematic review of clinical trials. Cancer
Gene Ther 2017;24:189‑93.
1. Joob B, Wiwanitkit V. Nanotechnology for health: A new useful 21. Gusella M, Bononi A, Modena Y, Bertolaso L, Franceschetti P, Menon D,
technology in medicine. Med J DY Patil Univ 2017;10:401-5. et al. Age affects pegylated liposomal doxorubicin elimination and
2. Ranganathan R, Madanmohan S, Kesavan A, Baskar G, tolerability in patients over 70 years old. Cancer Chemother Pharmacol
Krishnamoorthy YR, Santosham R, et al. Nanomedicine: Towards 2014;73:517‑24.
development of patient‑friendly drug‑delivery systems for oncological 22. Jameel S. Ethics in biotechnology and biosecurity. Indian J Med
applications. Int J Nanomedicine 2012;7:1043‑60. Microbiol 2011;29:331‑5.
3. Kasprzak B, Miskiel S, Markowska J. Nanooncology in ovarian cancer 23. Naurato N, Smith TJ. Ethical considerations in bioengineering research.
treatment. Eur J Gynaecol Oncol 2016;37:161‑3. Biomed Sci Instrum 2003;39:573‑8.
4. Schulte PA, Iavicoli I, Rantanen JH, Dahmann D, Iavicoli S, Pipke R, 24. Toth‑Fejel TT. Humanity and nanotechnology – Judging enhancements.
et al. Assessing the protection of the nanomaterial workforce. Natl Cathol Bioeth Q 2004;4:335‑64.
Nanotoxicology 2016;10:1013‑9. 25. King NM. Nanomedicine first‑in‑human research: Challenges for
5. Paradise J, Wolf SM, Kuzma J, Ramachandran G, Kokkoli E. informed consent. J Law Med Ethics 2012;40:823‑30.
Introduction: The challenge of developing oversight approaches to 26. Müller S. Magnetic fluid hyperthermia therapy for malignant brain
nanobiotechnology. J Law Med Ethics 2009;37:543‑5. tumors – An ethical discussion. Nanomedicine 2009;5:387‑93.
6. Paradise J, Tisdale AW, Hall RF, Kokkoli E. Evaluating oversight 27. Satalkar P, Elger BS, Shaw DM. Stakeholder views on participant
of human drugs and medical devices: A case study of the FDA and selection for first‑in‑human trials in cancer nanomedicine. Curr Oncol
implications for nanobiotechnology. J Law Med Ethics 2009;37:598‑624. 2016;23:e530‑7.
7. Wiwanitkit V, Sereemaspun A, Rojanathanes R. Effect of gold 28. Jotterand F, Alexander AA. Managing the “known unknowns”:
nanoparticles on spermatozoa: The first world report. Fertil Steril Theranostic cancer nanomedicine and informed consent. Methods Mol
2009;91:e7‑8. Biol 2011;726:413‑29.
8. Wiwanitkit V, Sereemaspun A, Rojanathanes R. Effect of gold 29. Resnik DB. Responsible conduct in nanomedicine research: Environmental
nanoparticle on the microscopic morphology of white blood cell. concerns beyond the common rule. J Law Med Ethics 2012;40:848‑55.
Cytopathology 2009;20:109‑10. 30. Panda JJ, Yandrapu S, Kadam RS, Chauhan VS, Kompella UB.
9. Wiwanitkit V, Sereemaspun A, Rojanathanes R. Gold nanoparticles and Retracted: Self‑assembled phenylalanine‑α,β‑dehydrophenylalanine
a microscopic view of platelets: A preliminary observation. Cardiovasc nanotubes for sustained intravitreal delivery of a multi‑targeted tyrosine
J Afr 2009;20:141‑2. kinase inhibitor. J Control Release 2016;237:186.

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