Abstract
AbstractSynthetic methodologies integrating hydrophobic drug delivery and biomolecular targeting with mesoporous silica nanoparticles are described. Transferrin and cyclic‐RGD peptides are covalently attached to the nanoparticles utilizing different techniques and provide selectivity between primary and metastatic cancer cells. The increase in cellular uptake of the targeted particles is examined using fluorescence microscopy and flow cytometry. Transferrin‐modified silica nanoparticles display enhancement in particle uptake by Panc‐1 cancer cells over that of normal HFF cells. The endocytotic pathway for these particles is further investigated through plasmid transfection of the transferrin receptor into the normal HFF cell line, which results in an increase in particle endocytosis as compared to unmodified HFF cells. By designing and attaching a synthetic cyclic‐RGD, selectivity between primary cancer cells (BT‐549) and metastatic cancer cells (MDA‐MB 435) is achieved with enhanced particle uptake by the metastatic cancer cell line. Incorporation of the hydrophobic drug Camptothecin into these two types of biomolecular‐targeted nanoparticles causes an increase in mortality of the targeted cancer cells compared to that caused by both the free drug and nontargeted particles. These results demonstrate successful biomolecular‐targeted hydrophobic drug delivery carriers that selectively target specific cancer cells and result in enhanced drug delivery and cell mortality.
References
60
Referenced
196
10.1038/nbt1006-1211
10.1021/jm00123a038
10.1111/j.1749-6632.1996.tb26391.x
10.1023/A:1018919224450
10.2174/1570163054866891
10.1016/j.jconrel.2009.08.011
10.1002/smll.200700005
10.1021/la8016084
10.1021/ja808137c
10.1039/b815009e
10.1021/nl901589y
10.1002/mabi.200500015
10.1038/359710a0
10.1021/cm0011559
10.1002/anie.200604488
10.1002/smll.200700903
10.1021/nn100690m
10.1021/ja1022267
10.1039/c0cc03905e
10.1021/ja110094g
10.1002/smll.201000538
10.1002/smll.200700493
10.1016/j.biomaterials.2008.07.007
10.1021/ja910846q
10.1002/adfm.200800753
10.1002/smll.201001459
10.1021/nn800072t
10.1039/b900427k
10.1002/smll.200902355
10.1021/mp050032z
10.1023/A:1010960900254
10.1023/B:PHAM.0000048188.69785.94
10.1038/nrm2799
10.1021/bm005584b
10.1016/S0142-9612(03)00343-0
10.1002/cphc.200301014
10.1073/pnas.0914140107
10.1364/OE.16.019568
10.1074/jbc.R000003200
10.1021/nn700370b
10.1016/S0165-6147(02)01989-2
10.1002/jcp.1041560128
10.1016/S0022-5347(17)39970-6
10.1016/j.ejca.2004.01.036
- For in‐vivo imaging integration of magnetic MRI contrast agent is often utilized. However to track nanoparticles in vitro optical monitoring using fluorescent markers cocondensed into the silica nanoparticles provides for easier observation given the experimental conditions.
10.1039/c0jm01258k
10.1002/cmmi.376
10.1021/cm051014c
10.1021/cm0210041
10.1016/j.ab.2006.02.023
10.1016/S0022-2313(96)00125-1
10.1016/0003-2697(70)90146-6
10.1016/0014-5793(91)81101-D
10.1111/j.1432-1033.1992.tb17495.x
10.1021/ja9603721
10.1007/s11095-005-5646-0
10.1016/S0040-4039(00)01060-1
10.1208/pt070232
10.1016/S0169-409X(02)00179-5
- With this system it is interesting to note that there was a 10‐fold increase in particle uptake by MDA‐MB 435 as compared to MCF‐7 cancer cells but only a 20% increase in cell killing over the passively uptaken phosphonated nanoparticles. This difference may be because of the difference in experimental design as particle uptake does not always directly correlate to its observed cytotoxic effect.
Dates
Type | When |
---|---|
Created | 14 years, 3 months ago (May 19, 2011, 4:57 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 7, 2023, 5:26 a.m.) |
Indexed | 2 months, 1 week ago (June 16, 2025, 2:24 p.m.) |
Issued | 14 years, 3 months ago (May 19, 2011) |
Published | 14 years, 3 months ago (May 19, 2011) |
Published Online | 14 years, 3 months ago (May 19, 2011) |
Published Print | 14 years, 1 month ago (July 4, 2011) |
@article{Ferris_2011, title={Synthesis of Biomolecule‐Modified Mesoporous Silica Nanoparticles for Targeted Hydrophobic Drug Delivery to Cancer Cells}, volume={7}, ISSN={1613-6829}, url={http://dx.doi.org/10.1002/smll.201002300}, DOI={10.1002/smll.201002300}, number={13}, journal={Small}, publisher={Wiley}, author={Ferris, Daniel P. and Lu, Jie and Gothard, Chris and Yanes, Rolando and Thomas, Courtney R. and Olsen, John‐Carl and Stoddart, J. Fraser and Tamanoi, Fuyuhiko and Zink, Jeffrey I.}, year={2011}, month=may, pages={1816–1826} }