Abstract
HeLa 229 cells were treated with methotrexate (MTX) and doxorubicin (DOX), utilizing fourth generation (G4), amine terminated poly(amidoamine) {PAMAM} dendrimer as the drug carrier. In vitro kinetic studies of the release of both MTX and DOX in presence and absence of G4, amine terminated PAMAM dendrimers suggest that controlled drug release can be achieved in presence of the dendrimers. The cytotoxicity studies indicated improved cell death by dendrimer-drug combination, compared to the control experiments with dendrimer or drug alone at identical experimental conditions. Furthermore, HeLa 229 cells were imaged for the first time utilizing the intrinsic emission from the PAMAM dendrimers and drugs, without incorporating any conventional fluorophores. Experimental results collectively suggest that the decreased rate of drug efflux in presence of relatively large sized PAMAM dendrimers generates high local concentration of the dendrimer-drug combination inside the cell, which renders an easy way to image cell lines utilizing the intrinsic emission properties of PAMAM dendrimer and encapsulated drug molecule.
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References
Ambade AV, Savariar EN, Thayumanavan S (2005) Dendrimers micells for controlled drug release and targeted delivery. Mol Pharm 2:264–272
Bellamy WT, Dalton WS, Kailey JM, Gleason MC, McCloskey TM, Dorr RT, Alberts DS (1988) Verapamil reversal of doxorubicin resistance in multidrug resistant human myeloma cells and association with drug accumulation and DNA damage. Cancer Res 48:6365–6370
Bronger H, König J, Kopplow K, Steiner HH, Ahmadi R, Mende CH, Keppler D, Nies AT (2005) ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Cancer Res 65:11419–11428
Carreno-Gomez B, Duncan R (2002) Compositions with enhanced oral bioavailability, USP: 20030211072
Chai M, Niu Y, Youngs WJ, Rinaldi PL (2001) Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques. J Am Chem Soc 123:4670–4678
Choi Y, Thomas T, Kotlyar A, Islam MT, Baker JR Jr (2005) Synthesis and functional evaluation of DNA-Assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting. Chem Biol 12:35–43
Emanuele AD, Attwood D (2005) Dendrimer-drug interactions. Adv Drug Deliv Rev 57:2147–2162
Emanuele AD, Jevprasesphant R, Penny J, Attwood D (2004) The use of a dendrimer-propanolol prodrug to bypass efflux transporters and enhance oral bioavailability. J Control Release 95:447–453
Esfand R, Tomalia DA (2001) Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 6:427–436
Fahmy TM, Schneck JP, Saltzman WM (2007) A nanoscopic multivalent antigen-presenting carrier for sensitive detection and drug delivery to T cells. Nanomedicine NBM 3:75–85
Florence AT, Sakthivel T, Toth I (2000) Oral uptake and translocation of a polylysine dendrimer with a lipid surface. J Control Rel. 65:253–259
Gillies ER, Frechét JMJ (2005) Dendrimers and dendritic polymers in drug delivery. Drug Discov Today 10:35–43
Gurdag S, Khandare J, Stapels S, Matherly LH, Kannan RM (2006) Activity of dendrimer-methotrexate conjugates on methotrexate-sensitive and- resistant cell lines. Bioconjug Chem 17:275–283
Jansen JFGA, Meijer EW, den Berg EMM (1995) The dendritic box: shape selective liberation of encapsulated guests. J Am Chem Soc 117:4417–4418
Larson CL, Tucker SA (2001) Intrinsic fluorescence of carboxylate-terminated polyamido amine dendrimers. Appl Spect 55:679–683
Lee WI, Bae Y, Bard AJ (2004) Strong blue photoluminescence and ECL from OH-terminated PAMAM dendrimers in the absence of gold nanoparticles. J Am Chem Soc 126:8358–8359
Maiti PK, Goddard WA III (2006) Solvent quality changes the structure of G8 PAMAM dendrimer, a disagreement with some experimental interpretations. J Phys Chem B 110:25628–25632
Maiti PK, Cağin T, Lin ST, Goddard WA III (2005) Effect of solvent and pH on the structure of PAMAM dendrimers. Macromolecules 38:979–991
Majoros IJ, Kezler B, Woehler S, Bull T, Baker JR Jr (2003) Acetylation of poly(amidoamine) dendrimers. Macromolecules 36:5526–5529
Majoros IJ, Thomas TP, Mehta CB, Baker JR Jr (2005) Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy. J Med Chem 48:5892–5899
Najlah M, Freeman S, Attwood D, Emanuele AD (2007) In vitro evaluation of dendrimer prodrugs for oral drug delivery. Int J Pharmaceutics 336:183–190
Nam HY, Nam K, Hahn HJ, Kim BH, Lim HJ, Kim HJ, Choi JS, Park J-S (2009) Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity. Biomaterials 30:665–673
Papagiannaros A, Dimas K, Papaioannou GT, Demetzos C (2005) Doxorubicin-PAMAM dendrimer complex attached to liposomes: cytotoxic studies against human cancer cell lines. Int J Pharam 302:29–38
Patri AK, Kukowska-Latallo JF, Baker JR Jr (2007) Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv Drug Deliv Rev 57:2203–2214
Raub TJ (2006) P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol Pharmaceutics 3:3–25
Shiraki N, Hamada A, Ohmura T, Tokunaga J, Oyama N, Nakano M (2001) Increase in doxorubicin cytotoxicity by inhibition of p-glycoprotein activity with lomerizine. Biol Pharm Bull 24:555–557
Thomas TP, Majoros IJ, Kotlyar A, Kukowska-Latallo JF, Bielinska A, Myc A, Baker JR Jr (2005) Targeting and inhibition of cell growth by an engineered dendritic nanodevice. J Med Chem 48:3729–3735
Wang D, Imae T (2004) Fluorescence emission from dendrimers and its pH dependence. J Am Chem Soc 126:13204–13205
Wang D, Imae T, Miki M (2007) Fluorescence emission from PAMAM and PPI dendrimers. J Colloid Interface Sci 306:222–227
Wartenberg M, Frey C, Diedershagen H, Ritgen J, Hescheler J, Sauer H (1998) Development of an intrinsic P-glycoprotein-mediated doxorubicin resistance in quiescent cell layers of large, multicellular prostate tumor spheroids. Int J Cancer 75:855–863
Acknowledgments
We are grateful to the Department of Science and Technology (DST), Govt. of India for the financial support (SR/S1/PC-26/2007) and Council of Scientific and Industrial Reasearch (CSIR), New Delhi, India for fellowship to BKB for this work.
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Biswal, B.K., Kavitha, M., Verma, R.S. et al. Tumor cell imaging using the intrinsic emission from PAMAM dendrimer: a case study with HeLa cells. Cytotechnology 61, 17–24 (2009). https://doi.org/10.1007/s10616-009-9237-5
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DOI: https://doi.org/10.1007/s10616-009-9237-5