opportunities and challenges for nanomedicines · zomer &van rheenen lab, hubrecht . 8-12-2015...
TRANSCRIPT
![Page 1: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/1.jpg)
8-12-2015
1
Opportunities and Challenges for
Nanomedicines
Ray Schiffelers
Laboratory Clinical Chemistry & Hematology
Vesicles
100 nm
![Page 2: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/2.jpg)
8-12-2015
2
Passive liposome targeting
Unmodified liposomes are rapidly cleared from the circulation
Depending on size (very small), lipid composition (very rigid), charge (slightly negative) etc.
![Page 3: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/3.jpg)
8-12-2015
3
Distribution of labeled erythrocytes and
200 nm EPC-liposomes after iv injection
Blood Liposomes
Passive liposome targeting
1978
![Page 4: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/4.jpg)
8-12-2015
4
Preventing liver and spleen uptake
Coating with poly(ethylene) glycol decelerates liposome uptake by MPS
Blood Liposomes
Distribution of labeled erythrocytes and 100 nm PEG-liposomes after iv injection
Passive liposome targeting
Laverman et al.
![Page 5: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/5.jpg)
8-12-2015
5
Extravasation through ‘leaky’ inflamed vasculature (EPR effect)
Uchegbu et al. 2008
![Page 6: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/6.jpg)
8-12-2015
6
Local extravasation
Rheumatoid Arthritis
Crommelin et al, 2002
Kaposi Sarcoma
Harrington et al. 2001
Local extravasation
synovitislung tumor
Harrington et al. 2001
Dams et al. 2000
![Page 7: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/7.jpg)
8-12-2015
7
Common denominator
Danger
bacteria/tumor cells/antibodies/lipid deposits/messengers
Increased capillary permeability
Influx inflammatory cells/blood
components
Chronic inflammatory
signaling
Vesicles
loading
![Page 8: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/8.jpg)
8-12-2015
8
Vesicles
![Page 9: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/9.jpg)
8-12-2015
9
mPEG-DSPEHSPCCholesterol
Doxorubicin-sulphate
Intratumoral concentrations 3-10x increased
![Page 10: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/10.jpg)
8-12-2015
10
Efficacy in metastatic breast cancer
M. E. R. O’Brien et al. Ann Oncol 2004;15:440-449
Figure 3. Rate of cardiac events versus cumulative anthracycline dose.
M. E. R. O’Brien et al. Ann Oncol 2004;15:440-449
European Society for Medical Oncology
![Page 11: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/11.jpg)
8-12-2015
11
Hand & Foot syndromeNew DLT
![Page 12: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/12.jpg)
8-12-2015
12
![Page 13: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/13.jpg)
8-12-2015
13
Extracellulaire vesicles
![Page 14: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/14.jpg)
8-12-2015
14
Extracellular vesicles
![Page 15: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/15.jpg)
8-12-2015
15
Zomer &Van Rheenen lab, Hubrecht
![Page 16: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/16.jpg)
8-12-2015
16
![Page 17: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/17.jpg)
8-12-2015
17
Local transfer
![Page 18: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/18.jpg)
8-12-2015
18
![Page 19: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/19.jpg)
8-12-2015
19
![Page 20: Opportunities and Challenges for Nanomedicines · Zomer &Van Rheenen lab, Hubrecht . 8-12-2015 16. 8-12-2015 17 Local transfer. 8-12-2015 18. 8-12-2015 19. 8-12-2015 20 Conclusion](https://reader033.vdocuments.us/reader033/viewer/2022042412/5f2bee76d01b23238f6e5937/html5/thumbnails/20.jpg)
8-12-2015
20
Conclusion
• EV offers a new angle for RNA delivery
• Exogenous loading is not straightforward
• Cell produced & loaded EV show activity in vivo
• Acceptor cells change phenotype