cancer historically agents given systemically – agents that kill rapidly dividing cells find...
TRANSCRIPT
![Page 1: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/1.jpg)
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
![Page 2: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/2.jpg)
![Page 3: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/3.jpg)
• Nanoparticles – drug throughout
• Nanocapsules – drug w/in coating
• PEGylation – makes stealthy
• Ligand – binds to cell receptor for targeting
![Page 4: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/4.jpg)
Tumor Vasculature• Irregularly shaped, big, and leaky• Lack of lymph drainage• High vessel density
![Page 5: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/5.jpg)
Passive Targeting EPR• Small drugs enter tumor and leave• Particles enter and stay– Long circulation time key
![Page 6: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/6.jpg)
Active Targeting• EPR + something that binds tumor cells
specifically
![Page 7: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/7.jpg)
Targeting
Interfere with signaling when bind (targeting ligand and drug)
Ab tethered to drug
Ligand + drug
depends upon over-expression of surface molecules by tumor cells
![Page 8: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/8.jpg)
Paige
![Page 9: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/9.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Paige
![Page 10: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/10.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
MoCRIC50=1.2 mM
MCF-7 IC50=0.8 mM
HT-29IC50=0.85 mM
DLD-1IC50=0.8 mM
Paige
![Page 11: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/11.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Shrinidhi
![Page 12: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/12.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Shrinidhi
![Page 13: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/13.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Shrinidhi
![Page 14: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/14.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Anna
![Page 15: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/15.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Anna
![Page 16: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/16.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Anna
![Page 17: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/17.jpg)
Daruwalla, Cancer Science, 2010; 101; 1866-1874
Felix
![Page 18: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/18.jpg)
Kevin
![Page 19: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/19.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410-
Kevin
![Page 20: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/20.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410-
Inseong
![Page 21: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/21.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410-
Inseong
![Page 22: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/22.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410-
Maura
backgroundnon-targetedpre-targeteddirect target
![Page 23: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/23.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410
Maura
![Page 24: Cancer Historically agents given systemically – Agents that kill rapidly dividing cells Find therapeutic dose Kills tumor cells w/o killing patient –](https://reader035.vdocument.in/reader035/viewer/2022081603/5697bfae1a28abf838c9c8ca/html5/thumbnails/24.jpg)
Lehtinen, PLOS One, 2012; 7(7); e41410-
Michael