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.