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Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

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Preclinical Studies on Nanocarrier-Mediated Delivery of Radiosensitizing Agents to Brain and Pancreatic Cancer with a Future Projection to Liver Cancer

Author(s): Peter Sminia*, Pei Pei Che, Ben J. Slotman and Elisa Giovannetti

Pp: 316-332 (17)

DOI: 10.2174/9789815039740122010010

* (Excluding Mailing and Handling)

Abstract

Radiotherapy is one of the primary treatment modalities in oncology. The
therapeutic effectiveness of irradiation is dependent on the balance between the tumor
control probability (TCP) and the normal tissue complication probability (NTCP), i.e.,
the induction of side effects. Combination treatment of irradiation with chemotherapy
targeted to a tumor or using immune-modulating agents could significantly benefit
from nanotechnology strategies, allowing localized delivery of therapeutic compounds
to the irradiated tumor volume. When used in combination with irradiation, drugs
should be selected on their interaction with the 6 R’s, the six Hallmarks of
Radiobiology, to sensitize the radiation effect on the molecular, cellular, and tissue
level, and in addition to that, positively impact the TCP/NTCP balance. This chapter
presents and discusses preclinical data on the combination of irradiation and
nanocarrier-mediated delivery of drugs in the brain, pancreatic, and liver cancer. Before
implementation into the clinical practice, nanotechnology demands further technical
and biological studies on drug loading efficacy, drug release, cellular and tissue uptake,
biodistribution, tumor-targeting methods, and administration routes to the patient.
Notwithstanding those challenges, the combination of local radiotherapy with tumortargeted
nanocarrier-delivered radiosensitizers, as well as the use of radiosensitizing
nanoparticles, are exciting developments with a great clinical prospect.

Keywords: Blood-brain barrier, Binimetinib, Brain tumour, Curcumin, GBM, Hallmarks of radiobiology, Hepatocellular carcinoma, Immune-modulating agents, Nanocarriers, Oncology, Pancreatic cancer, Radiosensitization, Radiotherapy, Six R ’s, Therapeutic agents.

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