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drainage, the TME has high IFP. This heterogeneity of the vasculature, high IFP, poor extravasation due to
sluggish blood flow, and larger distance between exchange vessels are all potential barriers to the delivery
of therapeutic agents to tumours. A rationally designed delivery system should overcome all these barriers
to reach deep tumour tissue. As the endothelial cells of tumour vasculature have longer gaps, and the IFP is
high, nanoparticles of proper size can inherently be accumulated in the tumour due to the EPR effect. This
is known as passive targeting. The surface of nanocarriers can also be coated with monoclonal antibodies
against receptor proteins overexpressed in proangiogenic tumour cells for active targeted drug delivery. The
vascular barrier can be further reduced by enhancing blood perfusion in the tumour and normalization
of tumour vasculature. Local delivery of mediators such as NO and CO enhance blood perfusion whereas
inhibition of proangiogenic pathways and the use of antiangiogenic agents help in the accumulation of
anticancer drugs loaded nanocarriers deep within tumour tissues. Furthermore, the use of sonoporation
and hyperthermia boosts nanocarrier mediated tumour-targeted drug delivery.

DECLARATIONS
Acknowledgments
The authors are grateful to the Guru Nanak Institute of Pharmaceutical Science & Technology and
Department of Biotechnology, University of Calcutta for providing literature resources and other software
facilities required for writing the manuscript.

Authors’ contributions
Contributed in writing the manuscript: Dastidar DG
Contributed in editing the manuscript: Chakrabarti G
Did the literature survey and prepared the diagrams: Ghosh D

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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