2.4 Phytochemical Nanoformulation/Derivatives/chemical analogues
for HNC treatment
Among various treatment strategies for HNC therapy use of phytochemical
loaded nanoparticles (NPs) are gaining popularity, due to their unique
magnetic, optical, mechanical, & thermal properties. NPs provide
enhanced permeability and retention (EPR) effect which results in easy
permeation into leaky tumor vessels and increased retention in the
tissues due to lack of lymphatic drainage. Phytochemical based
Neoformations/ nanoparticles can help in overcoming the limitation
associated with bioavability and increase their efficacy. The
phytochemical derived nanoparticles, their derivatives and analogs which
have been found effective for HNC prevention and treatment are listed in
Table 3 and discussed below.
Luteolin nanoparticles improved the bioavailabilty and were absorbed
directly by oral cavity epthilium (Walle et al. , 2005). Luteolin
nanoparticles significantly decreased the tumor growth of HNC cells bothin-vivo and in-vitro and displayed increased efficacy
(Majumdar et al. , 2014).
5-fluorouracil coencapsulated in PEGylated nanoliposomes along with
resveratrol improved the chemotherapeutic efficacy in head and neck
cancer (Mohan et al. , 2014).
In another study by Sulfikkarali et al (2013) Naringenin loaded
nanoparticles (NARNPs) were effective in inhibiting the tumor growth in
DMBA induced oral carcinogenesis model and showed anti-proliferative,
anti-lipid peroxidative and antioxidant effects. NARNPs were more
efficient than free NAR due to EPR effects. NARNPs exhibited sustained
release of the phytochemicals/drugs and resulted in prolonged exposure
of tumor cells to anticancer phytochemicals/drugs (Sulfikkarali et
al. , 2013).
Phospholipid complex loaded nanoparticles encapsulating Salvianolic acid
B were also found to be a potent drug for HNC. Cellular uptake of SalB
PLC-NPs complex (nano SalB) was significantly higher as compared to
free-salB in HN13 and HN30 cell lines. It was more potent in inhibiting
growth, arresting cell cycle and inducing apoptosis than free Sal B (Liet al. , 2016).
Ursolic acid (UA) and paclitaxel (PTX) co-loaded liposomes were also
found to be significantly more cytotoxic than PTX alone in head & neck
squamous cell carcinoma HSC-3 cells (Lv et al. , 2018). Cellular
uptake was increased and induced the apoptosis in HNC more powerfully
than PTX-LiP and free PTX.Hesperetin-Loaded Nanoparticles (HETNPs) were
also more effective than natural hesperetin in enhancing the levels of
endogenous fluorophores approx. to near normal range in DMBA-induced
hamster buccal pouch carcinogenesis model (Gurushankar et al. ,
2015).
Anticancer effect of a novel Indole-3-Carbinol derivative OSU-A9 was
reported in a number of HNC cell lines including SCC4, SCC15, SCC2095 as
well as in oral squamous cell carcinoma OSCC. The antiproliferative
effect was approximately 2 times higher. OSU-A9 induced ER stress and
ROS production and induce mitochondrial mediated apoptosis via
downregulating Akt and NF-κB signaling pathways (Weng et al. ,
2010).
A derivative of Kaempferol, Kaempfero3-O-rhamnoside also showed
cytotoxicity against CNE-1 (Human Nasopharyngeal carcinoma) and
inhibited the invasion and migration via inhibiting the RhoC,
Metastasis-associated gene 1 (MTA1), MMP7, MMP9. It also decreased EGFR
and Phosphorylation of ERK (Huang et al. , 2017).
All chemopreventive agents that show very good effects in-vitrodo not necessarily show same effects in human clinical trails in HNC.
Table 4 lists phytochemicals that are under clinical trials.