Paper
RSC Advances
(
i) the DOX incorporation is signicantly higher following the
treatment with DOX-b-CD-PNVP in all the cell lines tested,
ii) DOX-uptake from DOX-b-CD-PNVP compared to free DOX at
2 F. Haaf, A. Sanner and F. Straub, Polymers of
N-Vinylpyrrolidone: Synthesis, Characterization and Uses,
Polym. J., 1985, 17, 143–152.
(
microscopic level is signicantly higher in all the cell lines
tested, (iii) Intracellular DOX concentration in HEPG2 is
particularly signicantly higher compared to MCF-7 or, U2-OS.
Overall, the observed signicantly higher intracellular level of
DOX in cells treated with DOX-b-CD-PNVP compared to free
DOX suggests high drug delivery efficiency of the compound.
3 J. Chiefari, R. T. A. Mayadunne, G. Moad, E. Rizzardo and
S. H. Thang, 1999, PCT IntAppl W099/31144.
4 V. Coessens, T. Pintaver and K. Matyzaszewski, Functional
polymers by atom transfer radical polymerization, Prog.
Polym. Sci., 2001, 26, 337–377.
5 D. Wan, K. Satoh, M. Kamigaito and Y. Okamoto, Xanthate-
mediated radical polymerization of N-vinylpyrrolidone in
uoroalcohols for simultaneous control of molecular
Conclusions
weight and tacticity, Macromolecules, 2005, 38, 10397–10405.
R. Devasia, R. L. Bindu, N. Mougia and Y. Gnanou,
Controlled radical polymerization of N-vinylpyrrolidone by
reversible addition-fragmentation, Macromol. Symp., 2005,
6
In conclusion, tadpole-shaped b-cyclodextrin-tagged poly(N-
vinylpyrrolidone) (DOX-b-CD-PNVP) has been synthesised via
the click reaction of alkyne-terminated PNVP and azide-
functionalized b-CD. Formed polymer is characterized by
229, 8–17.
1
7 P. Bilalis, M. Pitsikalis and N. Hadjichristidis, Controlled
nitroxide-mediated and reversible addition-fragmentation
chain transfer polymerization of N-vinylpyrrolidone:
synthesis of block copolymers with styrene and 2-
vinylpyridine, J. Polym. Sci., Part A: Polym. Chem., 2006, 44,
659–665.
S. Yamago, B. Ray, K. Iida, J. I. Yoshida, T. Tada,
K. Yoshizawa, Y. Kwak, A. Goto and T. Fukuda, Highly
versatile organostibine mediators for living radical
polymerization, J. Am. Chem. Soc., 2004, 126, 13908–13909.
B. Ray, M. Kotani and S. Yamago, Highly controlled synthesis
of poly(N-vinylpyrrolidone) and its block copolymers by
organostibine-mediated living radical polymerization,
Macromolecules, 2006, 39, 5259–5265.
0 S. I. Yusa, S. Yamago, M. Sugahara, S. Morikawa,
T. Yamamoto and Y. Morishima, Thermoresponsivediblock
copolymers of poly(N-isopropylacrylamide) and poly(N-
vinyl-2-pyrroridone) synthesized via organotellurium-
mediated controlled radical polymerization (TERP),
Macromolecules, 2007, 40, 5907–5915.
H NMR, FTIR, and TGA studies. The complexing ability of
phenolphthalein with such polymer is lower than that of with
b-CD. Loading of DOX in b-CD-PNVP is evidenced from DLS
study. In vitro release study reveals the sustained DOX release
behaviour up to 25 and 48% in PBS solutions of pHs 7.4 and 6.4,
ꢂ
respectively, at 37 C. DOX-b-CD-PNVP is found to be effective in
8
intracellular transportation of doxorubicin, causing apoptosis,
and retards the growth of the tumor cells of diverse origin. Our
results suggest that DOX-b-CD-PNVP critically regulates the
proliferative capacity of tumor cells where doxorubicin is
specically used like the end stage breast cancer and hepato-
cellular carcinomas. The results in HEPG2 cells are particularly
encouraging since doxorubicin is one of the preferred drug to
treat hepatocellular carcinomas. Overall, results presented in
the current study demonstrate that DOX-loaded b-CD-PNVP can
be used in targeted delivery of doxorubicin more effectively
compared to doxorubicin alone.
9
1
Authors contributions
1
1 S. Yamago, E. Kayahara, M. Kotani, B. Ray, Y. Kwak, A. Goto
and T. Fukuda, Highly controlled living radical
Performed the experiments: NKV, VKP, SKH, KR, PS, KM, SS;
conceived and designed the experiments: BR, PPM, NM, NKV,
VKP, SKH, KR; analyzed the data: NKV, VKP, SKH, KR, NM, BR,
PPM; contributed reagents/materials/analysis tools: BR, PPM,
NM, DC, PM; wrote the paper: BR, PPM, NKV, VKP, KR, SKH.
polymerization
organobismuthines, Angew. Chem., Int. Ed., 2007, 46, 1304–
306.
through
dual
activation
of
1
1
2 X. Lu, S. Gong, L. Meng, C. Li, S. Yang and L. Zhang,
Controllable synthesis of poly(N-vinylpyrrolidone) and its
block copolymers by atom transfer radical polymerization,
Polymer, 2007, 48, 2835–2842.
Acknowledgements
We gratefully acknowledge the nancial supports from
the Department of Biotechnology (DBT), New Delhi, India,
through the grant nos BT/PR11490/BRB/10/675/2008 (PPM) and
BT/PR889/NNT/28/570/2011 (BR and PPM). VKP, and NKV
acknowledge CSIR, Government of India for the Research
Fellowships.
1
3 G. Pound, Z. Eksteen, R. Pfukwa, J. M. McKenzie,
R. F. M. Lange and B. Klumperman, Unexpected reactions
associated with the xanthate-mediated polymerization of
N-vinylpyrrolidone, J. Polym. Sci., Part A: Polym. Chem.,
2008, 46, 6575–6593.
1
4 G. Pound, F. Aguesse, J. B. McLeary, R. F. M. Lange and
B. Klumperman, Xanthate-mediated copolymerization of
vinyl monomers for amphiphilic and double-hydrophilic
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