Abstract：
AIM:To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. MAIN METHODS:NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. KEY FINDINGS:Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. SIGNIFICANCE:Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy.
journal_name
Life Scijournal_title
Life sciencesauthors
Sreeja S,Krishnan Nair CKdoi
10.1016/j.lfs.2017.12.036subject
Has Abstractpub_date
2018-02-15 00:00:00pages
71-80eissn
0024-3205issn
1879-0631pii
S0024-3205(17)30686-0journal_volume
195pub_type
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