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Cancer. Historically agents given systemically Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient Lots of side effects Localized/targeted delivery is the holy grail Nanomedicine !! Also protection from degradation and increased solubility.
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Cancer • Historically agents given systemically • Agents that kill rapidly dividing cells • Find therapeutic dose Kills tumor cells w/o killing patient • Lots of side effects • Localized/targeted delivery is the holy grail • Nanomedicine!! • Also protection from degradation and increased solubility
Nanoparticles – drug throughout • Nanocapsules – drug w/in coating • PEGylation – makes stealthy • Ligand – binds to cell receptor for targeting
Tumor Vasculature • Irregularly shaped, big, and leaky • Lack of lymph drainage • High vessel density
Passive Targeting EPR • Small drugs enter tumor and leave • Particles enter and stay • Long circulation time key
Active Targeting • EPR + something that binds tumor cells specifically
Targeting depends upon over-expression of surface molecules by tumor cells Interfere with signaling when bind (targeting ligand and drug) Ab tethered to drug Ligand + drug
Ashley Daruwalla, Cancer Science, 2010; 101; 1866-1874
Ashley Daruwalla, Cancer Science, 2010; 101; 1866-1874
Julianne Daruwalla, Cancer Science, 2010; 101; 1866-1874
Julianne Daruwalla, Cancer Science, 2010; 101; 1866-1874
Julianne Daruwalla, Cancer Science, 2010; 101; 1866-1874
Kelsey Daruwalla, Cancer Science, 2010; 101; 1866-1874
Kelsey Daruwalla, Cancer Science, 2010; 101; 1866-1874
Kelsey Daruwalla, Cancer Science, 2010; 101; 1866-1874
Kelsey Daruwalla, Cancer Science, 2010; 101; 1866-1874
Philicia Lehtinen, PLOS One, 2012; 7(7); e41410-
Philicia Lehtinen, PLOS One, 2012; 7(7); e41410-
Philicia Lehtinen, PLOS One, 2012; 7(7); e41410-
Suzy Lehtinen, PLOS One, 2012; 7(7); e41410-
Suzy Lehtinen, PLOS One, 2012; 7(7); e41410
Suzy Lehtinen, PLOS One, 2012; 7(7); e41410-