NDLI: A low toxic synthetic dendrimer conjugated podophyllotoxin nanodevice with potent antitumor activity against the DMBA/TPA induced mouse skin carcinogenesis model

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A low toxic synthetic dendrimer conjugated podophyllotoxin nanodevice with potent antitumor activity against the DMBA/TPA induced mouse skin carcinogenesis model

Content Provider	Semantic Scholar
Author	Sk, Ugir Hossain Patial, Vikram Sharma, Supriya
Copyright Year	2015
Abstract	Natural podophyllotoxin (PODO) is an anticancer drug that functions as an anti-mitotic agent and inhibits tubulin polymerization. However, high toxicity and low bioavailability limit its anticancer applications. To minimize toxicity and enhance solubility under physiological conditions, we conjugated PODO to a poly(amidoamine) (PAMAM) dendrimer to generate sustained-release nanodevices (D-PODO). Free PODO and its dendrimer conjugates were screened for toxicity in Swiss albino mice, and the dose-dependent antitumor activity of D-PODO was evaluated in a two-stage mouse skin carcinogenesis model. The results showed that 8 mg kg−1 D-PODO was nontoxic, whereas the same dose of PODO was highly toxic, as indicated by mortality, biochemical and histopathological studies. An antitumor therapeutic study using D-PODO in tumor-bearing mice revealed a 50–60% inhibition of skin tumor formation. Histopathology and immunohistochemistry studies revealed that D-PODO treatment reduced epithelial hyperplasia, and induced apoptosis by increasing the Bax to Bcl-2 ratio and reducing NF-κB expression. Importantly, the D-PODO conjugate was less toxic than PODO, and inhibited skin tumor progression effectively.
Starting Page	1204
Ending Page	1213
Page Count	10
File Format	PDF HTM / HTML
DOI	10.1039/C5TX00112A
Alternate Webpage(s)	http://www.rsc.org/suppdata/c5/tx/c5tx00112a/c5tx00112a1.pdf
Alternate Webpage(s)	https://doi.org/10.1039/C5TX00112A
Volume Number	4
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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