The AAPS Journal

, 21:57 | Cite as

Targeting Cancer Via Resveratrol-Loaded Nanoparticles Administration: Focusing on In Vivo Evidence

  • Ana Cláudia SantosEmail author
  • Irina Pereira
  • Mariana Magalhães
  • Miguel Pereira-Silva
  • Mariana Caldas
  • Laura Ferreira
  • Ana Figueiras
  • António J. Ribeiro
  • Francisco Veiga
Review Article


Resveratrol (RSV) is a polyphenol endowed with potential therapeutic effects in chronic diseases, particularly in cancer, the second leading cause of death worldwide in the twenty-first century. The advent of nanotechnology application in the field of drug delivery allows to overcome the constrains associated with the conventional anticancer treatments, in particular chemotherapy, reducing its adverse side effects, off target risks and surpassing cancer multidrug chemoresistance. Moreover, the use of nanotechnology-based carriers in the delivery of plant-derived anticancer agents, such as RSV, has already demonstrated to surpass the poor water solubility, instability and reduced bioavailability associated with phytochemicals, improving their therapeutic activity, thus prompting pharmaceutical developments. This review highlights the in vivo anticancer potential of RSV achieved by nanotherapeutic approaches. First, RSV physicochemical, stability and pharmacokinetic features are described. Thereupon, the chemotherapeutic and chemopreventive properties of RSV are underlined, emphasizing the RSV numerous cancer molecular targets. Lastly, a comprehensive analysis of the RSV-loaded nanoparticles (RSV-NPs) developed and administered in different in vivo cancer models to date is presented. Nanoparticles (NPs) have shown to improve RSV solubility, stability, pharmacokinetics and biodistribution in cancer tissues, enhancing markedly its in vivo anticancer activity. RSV-NPs are, thus, considered a potential nanomedicine-based strategy to fight cancer; however, further studies are still necessary to allow RSV-NP clinical translation.


anticancer activity in vivo administration molecular targets nanoparticles resveratrol 





ATP-binding cassette


Alkali lignin


Acute lymphoblastic leukemia


Activator protein-1


Blood-brain barrier


Biopharmaceutical Classification System


Bovine serum albumin


Blood-tumor barrier


Chemical Abstracts Service


Anti-cellular inhibitor of apoptosis protein


Central nervous system






Doxorubicin hydrochloride




Drug loading




Dimethyl sulfoxide


Differential scanning calorimetry


Encapsulation efficiency




Enhanced permeability and retention


Forkhead box O3 protein


Hypoxia-inducible factor-1α


Heregulin-beta 1


Human serum albumin


Heat shock protein


Half maximal inhibitory concentration






Inhibitor of apoptosis protein


Low-density lipoprotein


Lewis lung carcinoma


Lipid-core nanocapsule

log Po/w

1-Octanol/water partition coefficient


Mitogen-activated protein kinases


Macrophage inhibitory cytokine-1


Matrix metalloproteinase-2


Methoxy polyethylene glycol


Mononuclear phagocytic system


Mammalian target of rapamycin


Nuclear factor kappa B


Nanostructured lipid carrier


Non-obese diabetic/severe combined immunodeficient




Non-small cell lung cancer


Poly (ADP-ribose) polymerase


Phosphate-buffered saline




Polyethylene glycol


Propidium iodide




Protein kinase I


Polylactic acid


Polyvinyl alcohol


Reticuloendothelial system




Rho-associated kinase


Reactive oxygen species




Solid lipid nanoparticle


Apparent terminal elimination half-life








Simultaneous thermogravimetry and differential scanning calorimetry




Terminal deoxynucleotidyl transferase dUTP nick end labeling




Vascular endothelial growth factor


World Health Organization


X-linked inhibitor of apoptosis protein


Zeta potential


Funding Information

This work was funded from Portugal National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência) through project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020). It was supported as well by the grants FCT PTDC/CTM-BIO/1518/2014 and FCT PTDC/BTM-MAT/30255/2017 from the Portuguese Foundation for Science and Technology (FCT) and the European Community Fund (FEDER) through the COMPETE2020 program. The authors wish to acknowledge Fundação para a Ciência e a Tecnologia (FCT), the Portuguese Agency for Scientific Research, for financial support through the Research Project POCI-01-0145-FEDER-016642, and through the individual doctoral grant attributed to Irina Pereira, together with the Programa Operacional Capital Humano (POCH), with the reference SFRH/BD/136892/2018.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Ana Cláudia Santos
    • 1
    • 2
    Email author
  • Irina Pereira
    • 1
    • 2
  • Mariana Magalhães
    • 1
    • 2
  • Miguel Pereira-Silva
    • 1
  • Mariana Caldas
    • 1
  • Laura Ferreira
    • 1
  • Ana Figueiras
    • 1
    • 2
  • António J. Ribeiro
    • 1
    • 3
  • Francisco Veiga
    • 1
    • 2
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacyUniversity of CoimbraCoimbraPortugal
  2. 2.REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of PharmacyUniversity of CoimbraCoimbraPortugal
  3. 3.i3S, Group Genetics of Cognitive DysfunctionInstitute for Molecular and Cell BiologyPortoPortugal

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