1. Organic nanoparticle mediated photo-triggered delivery of Curcumin
-An effective tool for preventing cancer
Sourav Sarkar
Organic & Biomaterial Chem. Lab
POSTECH
Date: 18th May’ 2016

2. Source: GLOBOCAN 2012, Cancer Incidence and Mortality Worldwide

3. Anticancer potential of curcumin: preclinical and clinical studies.
BB Aggarwal, A Kumar, AC Bharti, Anticancer res, 23(1); 363, 2003
Bioavailability of curcumin: problems and promises.
P Anand, AB Kunnumakkara, RA Newman, BB Aggarwal, ‎Mol. Pharm, 4(6); 807, 2007
Curcumin: the Indian solid gold.
BB Aggarwal, C Sundaram, N Malani, H Ichikawa, Springer US, 2007

4. What is Curcumin..?
A secondary metabolite found in the plant Curcuma longa, well known as turmeric.
Extraction
In solution

5. Applications at a glance
Anti-cystic fibrosis
Anti-HIV
Anti-rheumatic
Alzeimer disease
Anti-oxidant
Anti-microbial
Cardiotoxicity
Anti-inflamatory
Curcumin vs. Other anticancer drugs:
Natural source (Up to 3 weight % from turmeric)
No toxicity in overdose (Intake up to 12g/day for 4 weeks shows no side effect)
Nutrition and cancer, 55(2); 126–131, 2006

6. Problems in Curcumin Delivery..!!
Undergoes rapid metabolism:
Very low solubility in aqueous medium:
L Shen and HF Ji, Trends Mol. Med. 18; 138, 2012
M Salem, S Rohani, ER Gillies, RSC Adv. 4; 10815, 2014

7. Photo-Favorskii rearrangement
Fundamental idea:
J. Org. Chem., 78; 1718, 2013

8. Monitoring the process using fluorophore tagging:
ESIPT process in o-Hydroxybenzothiazole group:

9. A solution towards solubility
Introduction of tert-butyl group can increase solubility by prohibiting molecular stacking.
Organic & Biomolecular Chemistry, 12(40), 7914; 2014 

10. Nano-particles has reasonable cancer cell specificity..!!
Nanocarriers
Liposomes
Carbon nanotubes
Dendrimers
Micelles
Peptide nanofibers
Advantages
Solubility
Stability
Specificity
Non-toxicity
J Control Release, 172(1): 48-61, 2013 Nanoscale, 5(19): , 2013 Anticancer Res, 34(1): , 2014 Biomaterials, 33(24): , 2012

11. Synthesis of the Drug-Carrier conjugate
Bioorganic & Medicinal Chemistry Letters, 20(6), 1939; 2010
Angewandte Chemie, International Edition, 52(44), 11632; 2013
Angewandte Chemie International Edition, 55, 1; 2016

12. Future directions Real-time monitoring & in-vivo imaging:
One photon fluorophore can be modified into a two-photon fluorophore which will enable us deep tissue imaging to explore the exact behaviour of the carrier-drug conjugate inside the tissue.
One photon
Two photon
Possibly two-photon active

13. Increasing photo-reactivity:
Ester group has been reported to have significant photo sensitivity (more than aryloxy).
Aryloxy group
Question is whether carbonate can be a substitute for ester or not..??
Chem. Commun., 48; 3518, 2012,

14. Conclusion
Designed drug delivery system performs four important tasks. It serves as a..
Nanocarrier for drug delivery
Phototrigger for the drug release
Fluorescent chromophore for cell imaging
Detector for real time-monitoring of drug release.

15. Thank you..!!

16. Photo Dynamic Therapy PDT drugs Amount Average price Photofrin 75 mg
3300 USD
Visudyne
15 mg
1000 USD
Metvix cream
2 g
500 USD

17. Mechanism of action:
Cell Cycle Arrest Suppression of the Antiapoptotic Proteins Induction of Apoptotic Signals Modulation of MicroRNAs Modulation of Wnt/β-Catenin Signaling Inhibition of Nuclear Factor-κB Modulation of Protein Kinases Modulation of Proteasome Activation Epigenetic Regulation