Review Article
Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges

https://doi.org/10.1016/j.nano.2019.102139Get rights and content

Abstract

The clinical translation of new cancer theranostic has been delayed by inherent cancer’s heterogeneity. Additionally, this delay has been enhanced by the lack of an appropriate in vitro model, capable to produce accurate data. Nanoparticles and microfluidic devices have been used to obtain new and more efficient strategies to tackle cancer challenges. On one hand, nanoparticles-based therapeutics can be modified to target specific cells, and/or molecules, and/or modified with drugs, releasing them over time. On the other hand, microfluidic devices allow the exhibition of physiologically complex systems, incorporation of controlled flow, and control of the chemical environment. Herein, we review the use of nanoparticles and microfluidic devices to address different cancer challenges, such as detection of CTCs and biomarkers, point-of-care devices for early diagnosis and improvement of therapies. The future perspectives of cancer challenges are also addressed herein.

Graphical Abstract

The translation of new approaches for cancer theranostic has been delayed. One of the reasons behind it is the lack of an in vitro model capable to produce accurate data. In this reasoning, microfluidic devices and nanoparticles have been pursued to develop new and improved strategies to face different cancer challenges. This document overviews the recent reports that encompass new strategies for the detection of CTCs and biomarkers, for the development of point-of-care devices for early diagnosis, and for the improvement of therapies.

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Section snippets

CTCs capture platforms

The development of non-invasive methods for early cancer diagnosis is one of the main targets that could improve survival rates. CTCs are cells that migrate from the primary tumour into blood circulation, homing in distant organs and initiating the formation of metastasis. Due to this behaviour, CTCs have been emerging as the focus in the development of new diagnostic techniques. In fact, one can envisage the use of CTCs for timely diagnosis; prognosis of clinical outcomes; and prediction of

Biomarker detection platforms

Although there are several biomarkers associated with different cancer stages, its quantification is still a challenge due to the lack of proper measurement methods. Several technologies have been a motif of study, including enzyme-linked immunosorbent assay (ELISA) for protein biomarkers detection and polymerase chain reaction (PCR) for nucleic acid detection. However, these processes include several steps, resulting in time-consuming methods. To overcome these issues, nanoparticles and

Portable point-of-care devices

The development of portable point-of-care devices is important for the detection of specific biomarkers on-demand, and quickly and easily, supporting clinical decisions (Figure 6). Most of the portable point-of-care devices developed were microfluidic paper-based devices established for electrochemical signals detection.74., 75. Paper has several advantages, such as do not involve any external devices for fluidic transportation, since it occurs via capillary action; involves small volumes; is

Microfluidic devices and nanoparticles for therapies’ improvement

Currently, therapies have shown different efficiencies within the same tumour, hindering its approval by the Food and Drug Administration (FDA), and thus, its translation into clinics. In fact, during the first semester of 2019, the FDA approved a very limited amount of new drugs for the treatment of cancer as summarized in Table 2.90 That types of drugs were developed based on their interaction with specific molecules with the intent to enhance their efficiency while decreasing any deleterious

Conclusions and future directions

Traditional cancer diagnosis tools are still limited in their sensitivity and specificity. Therefore, new techniques have been pursued, such as the detection of CTCs and biomarkers.

On one hand, there is an incredible interest in the detection of CTCs due to their evident association with cancer progression. Several approaches concerning the use of EpCAM for CTCs detection were studied and even reach the clinic. But the addition of nanoparticles and microfluidic devices allowed to go further,

Acknowledgements

F.R. Maia acknowledges Portuguese Foundation for Science and Technology (FCT) for her work contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS5). J. M. Oliveira thanks FCT for his distinction attributed under the FCT Investigator program (IF/01285/2015).

References (109)

  • Z. Zhai et al.

    Muhammad, et al

    A microfluidic surface-enhanced Raman spectroscopy approach for assessing the particle number effect of AgNPs on cytotoxicity. Ecotoxicology and Environmental Safety.

    (2018)
  • H. Zhang et al.

    Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Analytica chimica acta.

    (2013)
  • C. Wang et al.

    Simultaneous isolation and detection of circulating tumor cells with a microfluidic silicon-nanowire-array integrated with magnetic upconversion nanoprobes

    Biomaterials.

    (2015)
  • M.C. Giuffrida et al.

    Ultrasensitive detection of lysozyme in droplet-based microfluidic devices

    Biosensors and Bioelectronics.

    (2018)
  • F.G. Ortega et al.

    Epithelial cancer biomarker EpCAM determination in peripheral blood samples using a microfluidic immunosensor based in silver nanoparticles as platform

    Sensors and Actuators B: Chemical.

    (2015)
  • R. Seenivasan et al.

    Microfluidic-integrated patterned ITO immunosensor for rapid detection of prostate-specific membrane antigen biomarker in prostate cancer

    Biosensors & bioelectronics.

    (2017)
  • S. Li et al.

    Gold nanoparticle-based low limit of detection love wave biosensor for carcinoembryonic antigens

    Biosensors & bioelectronics.

    (2017)
  • X. Yu et al.

    On-chip dual detection of cancer biomarkers directly in serum based on self-assembled magnetic bead patterns and quantum dots

    Biosensors & bioelectronics.

    (2013)
  • H. Zhang et al.

    Microfluidic beads-based immunosensor for sensitive detection of cancer biomarker proteins using multienzyme-nanoparticle amplification and quantum dots labels

    Biosensors & bioelectronics.

    (2013)
  • J.V. Jokerst et al.

    Nano-bio-chips for high performance multiplexed protein detection: determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels

    Biosensors & bioelectronics.

    (2009)
  • P.R. Chandran et al.

    Chapter 14 – Gold Nanoparticles in Cancer Drug Delivery

  • B. Wei et al.

    Graphene nanocomposites modified electrochemical aptamer sensor for rapid and highly sensitive detection of prostate specific antigen

    Biosensors & bioelectronics.

    (2018)
  • Y. Wang et al.

    Label-free microfluidic paper-based electrochemical aptasensor for ultrasensitive and simultaneous multiplexed detection of cancer biomarkers

    Biosensors and Bioelectronics.

    (2019)
  • F. Bahavarnia et al.

    Paper based immunosensing of ovarian cancer tumor protein CA 125 using novel nano-ink: A new platform for efficient diagnosis of cancer and biomedical analysis using microfluidic paper-based analytical devices (μPAD)

    International Journal of Biological Macromolecules.

    (2019)
  • Y. Fan et al.

    A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices

    Biosensors & bioelectronics.

    (2017)
  • W. Liu et al.

    Core-shell Fe3O4-Au magnetic nanoparticles based nonenzymatic ultrasensitive electrochemiluminescence immunosensor using quantum dots functionalized graphene sheet as labels

    Analytica chimica acta.

    (2013)
  • Y. Chen et al.

    Paper-based fluorometric immunodevice with quantum-dot labeled antibodies for simultaneous detection of carcinoembryonic antigen and prostate specific antigen

    Mikrochimica acta.

    (2019)
  • K. Kadimisetty et al.

    3D-printed supercapacitor-powered electrochemiluminescent protein immunoarray

    Biosensors & bioelectronics.

    (2016)
  • D. Kalinowska et al.

    Studies on effectiveness of PTT on 3D tumor model under microfluidic conditions using aptamer-modified nanoshells

    Biosensors and Bioelectronics.

    (2019)
  • Y. Chen et al.

    A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems

    Analytica chimica acta.

    (2018)
  • G. Sarfati et al.

    Targeting of polymeric nanoparticles to lung metastases by surface-attachment of YIGSR peptide from laminin

    Biomaterials.

    (2011)
  • Stewart BW, Wild CP. World Cancer Report 2014:...
  • J.A. Joyce et al.

    Microenvironmental regulation of metastasis

    Nat Rev Cancer.

    (2009)
  • F. Meric-Bernstam et al.

    Overcoming implementation challenges of personalized cancer therapy

    Nat Rev Clin Oncol.

    (2012)
  • M.G. Krebs et al.

    Circulating tumour cells: their utility in cancer management and predicting outcomes

    Ther Adv Med Oncol.

    (2010)
  • D.T. Miyamoto et al.

    Circulating tumour cells-monitoring treatment response in prostate cancer

    Nat Rev Clin Oncol.

    (2014)
  • A.M. Chakrabarty et al.

    Bacterial proteins and peptides in cancer therapy: today and tomorrow

    Bioengineered.

    (2014)
  • H. Zhu et al.

    Nucleic acid aptamer-mediated drug delivery for targeted cancer therapy

    ChemMedChem.

    (2015)
  • P.L. Patel et al.

    Patel MR

    (2015)
  • B. Virupakshappa

    Applications of nanomedicine in oral cancer

    Oral Health Dent Manag.

    (2012)
  • H. Boulaiz et al.

    Nanomedicine: application areas and development prospects

    Int J Mol Sci.

    (2011)
  • X. Zhang et al.

    A pH-sensitive nanosystem based on carboxymethyl chitosan for tumor-targeted delivery of daunorubicin

    Journal of biomedical nanotechnology.

    (2016)
  • X. Wei et al.

    Folate receptor-targeted and GSH-responsive carboxymethyl chitosan nanoparticles containing covalently entrapped 6-mercaptopurine for enhanced intracellular drug delivery in leukemia

    Mar Drugs.

    (2018)
  • H. Peng et al.

    Polymeric multifunctional nanomaterials for theranostics

    Journal of Materials Chemistry B.

    (2015)
  • P.M. Valencia et al.

    Microfluidic technologies for accelerating the clinical translation of nanoparticles

    Nature Nanotechnology.

    (2012)
  • L.M. Bellan et al.

    Current trends in nanobiosensor technology

    Wiley interdisciplinary reviews Nanomedicine and nanobiotechnology.

    (2011)
  • H. Yun et al.

    Cell manipulation in microfluidics

    Biofabrication.

    (2013)
  • Rusling JF, Bishop GW, Doan N, Papadimitrakopoulos F. Nanomaterials and biomaterials in electrochemical arrays for...
  • R.V. Devi et al.

    Nanomaterials for early detection of cancer biomarker with special emphasis on gold nanoparticles in immunoassays/sensors

    Biosensors & bioelectronics.

    (2015)
  • M. Jarvis et al.

    Microfluidic co-culture devices to assess penetration of nanoparticles into cancer cell mass

    Bioengineering & translational medicine.

    (2017)

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