BÁO CÁO KẾT QUẢ NGHIÊN CỨU KHOA HỌC, CÔNG NGHỆ VÀ ĐÀO TẠO

Introduction- Background Radiation Chemotherapy Hormone therapy Surgery Targeted therapy Current therapies for cancer Chemotherapy – a common therapy in breast cancer Chemotherapy – a

BÁO CÁO KẾT QUẢ NGHIÊN CỨU KHOA HỌC, CÔNG NGHỆ VÀ ĐÀO TẠO

Nguyễn Văn Cường

Đại học Công nghiệp Tp HCM

OVERVIEW OF SCIENTIFIC RESEARCH,

TECHNOLOGY AND TRAINING

Research interest

2

Introduction- Background

Radiation

Chemotherapy

Hormone therapy

Surgery

Targeted therapy

Current therapies for cancer

Chemotherapy – a common therapy

in breast cancer

Chemotherapy – a common therapy

in breast cancer

Anti-cancer drugs

Kill

Cancer cells

Blood stream Most parts of body

Enter Reach

Disrupt

proliferate or migrate

 Used to treat all stages of breast cancer

 Used before and after surgery

 Combine with other therapies

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1 Polymeric micelles for drug delivery

Drug Delivery for cancer treatment

Nanocarriers reach

tumors via the

enhanced

permeability and

retention (EPR) effect

Drugs alone diffuse in and out the tumor blood vessels

Ligands grafted at the

surface of nanocarriers

bind to receptors

4

Introduction- Background

Research structure

1 Polymeric micelles for drug delivery

6 Synthesis of triblock copolymer

Poly(ε-caprolactone) (PCL)caprolactone) (PCL)

Poly(ethylene glycol) (PEG)

Linear Polymeric micelles for drug delivery

1 Polymeric nanoparticle for drug delivery

N,N'-dicyclohexylcarbodiimide (DCC)

4-Dimethylaminopyridine (DMAP)

Poly(ethylene glycol) (PEG) Poly(ε-caprolactone) (PCL)caprolactone) (PCL)

1 Journal of Nanoscience and Nanotechnology 2008 (SCI, IF = 1,56)

2 Journal of Applied Polymer Science, 2010 (SCI, IF= 1,67 )

3 Journal of Nanoscience and Nanotechnology, 2011 (SCI, IF =1,56)

4 Advances In Natural Sciences-Nanoscience and Nanotechnology, 2010 (SCIE, IF =1,56)

5 Polymers, 2016 (SCIE, IF = 3.681) (Accepted 8/2016) 7

Linear Polymeric micelles for drug delivery

Block copolymers

Nanocarriers

Publication

1 Polymeric nanoparticle for drug delivery

Doxorubicin (DOX) Self-assembly

Animal study of DOX-caprolactone) (PCL)loaded Linear micelles

Biodistribution of DOX-loaded micelle (a) and free DOX (b) after administration at the equivalent 5

mg/kg DOX

1 Polymeric nanoparticle for drug delivery

Treated with free DOX Treated with micellar DOX

8

Ligand-star-shaped copolymers

1 Polymeric micelles for drug delivery

Shape of nanoparticle

by AFM image

N,N'-dicyclohexylcarbodiimide (DCC) 4-Dimethylaminopyridine (DMAP)

p-nitrophenyl chloroformate (p-NPC)

Dicholoromethane (DCM)

Synthesis of folic-grafted star shaped copolymer

A Caveosome

An Endosome

Caveolae-mediated endocytosis FR-mediated endocytosis

Plasma membrane

, FR: Folate receptor :

Doxorubicin : Caveolae , FOL : Folic acid

Folic-star-shaped copolymers

1 Journal of Nanoscience and Nanotechnology, 2011 (SCI, IF = 1,56)

2 Journal of Biomaterials Science, Polymer Ed , 2011 (SCI, IF = 1,64)

3 Journal of Materials Chemistry, 2012 (SCI, IF = 6.62, Citation = 43)

4 Polymers, 2014 (SCIE, IF = 3.681)

Nanocarriers

Pathway of Nanocarriers into cells

In-vitro Dox released from star-shaped FOL-PEG-PCL micelles

Doxorubicin released from Polymeric Micelles

1 Polymeric micelles for drug delivery

In-vitro Cytotoxicity DOX-caprolactone) (PCL)Loaded FOL-caprolactone) (PCL)PEG-caprolactone) (PCL)PCL Micelle

In vitro cytotoxicity of free DOX and DOX-loaded star-shaped

FOL-PEG-PCL micelle in human MCF-7 (a) and MCF-7/adr (b) breast cancer cells

1 Polymeric micelles for drug delivery

IC50

IC50

Confocal Image of DOX-caprolactone) (PCL)Loaded FOL-caprolactone) (PCL)PEG-caprolactone) (PCL)PCL Micelle in MCF-caprolactone) (PCL)7 Cells

1 Polymeric micelles for drug delivery

Overall Discussion

Sample Mn,nmr CMC

(mg/mL)

Micellar size (nm)a

Micellar size (nm)b

DLE (%) DLC (%)

EC36E (Linear) 13,700 5.6×10-3 40.2 50.5 26.4 3.7

PCL100-PEEP50

(Star-shape)

18,945 24×10-3 150.0 156.1 55.2 4.1

FOL-PEG-PCL

(Star-shape)

15,833 62.5×10-3 110.5 148.2 90 13

a Micelles before DOX-loading (average size with ten measurements); DLE: Drug loading

efficiency; DLC: Drug loading content

b Micelles after DOX-loading; NA: not available

Characteristics of prepared copolymeric micelles

1 Polymeric micelles for drug delivery

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Current study and future direction Theranostic therapy

Theranostic is a combination of diagnostic and therapy

Targeting drug delivery

combined with imaging agent

Targeting drug delivery

combined with imaging agent

1 Polymeric micelles for drug delivery

2Q-MEH: an imaging agent

Preparation of 2QMEH-loaded PEG-PCL micelles

a) 2QMEH loaded micelles under visible

light

2QMEH loaded micelles under

UV-light

PEG-PCL micelles before and

after loading 2Q-MEH

2Q-MEH loaded micelles under visible light (a) and under UV-light (b)

Preliminary Results

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2Q-MEH: an imaging agent

2 Nanomaterial for wastewater treatment

1 Journal of Nano Research, 2015 (SCIE, IF = 0.49)

2 Advances In Natural Sciences-Nanoscience and Nanotechnology, 2014 (SCIE, IF = 1,581)

Nanocomposite with magnetic

properties:

- Magnetic Hydroxyapatite

- Magnetic CNT nanocomposite

- Magnetic Chitosan-PAA/Fe3O4

Preparation of photocatalyst based on metallic nanomaterials with magnetic properties:

- Core-shell magnetic metal-doped ZnO nanoparticle

- Magnetic nanocomposite of chitosan/metal-ZnO and chitosan/metal-ZnO

Suspension Separate by gravity Separate by an external magnet

 60 scientific publications and 01 book chapter: 9 SCI, 11 SCIE, 1

ISI, 2 Scopus, 28 domestic article and 9 conference papers

 Projects

PI of 2 IUH-Project (2012-2013 and 2015-2016)

Member of 02 IUH-Project (2013-2014 and 2014-2015)

Member of MOIT–Project (2013-2015)

Member of Nafosted Project (2013-2015)

Research and training output

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5 typical articles

Author H-caprolactone) (PCL)index = 10

1 Targeted delivery of doxorubicin to human breast cancers by folate-decorated star-shaped PEG-PCL micelle 43

2 Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer 32

3 Nano-sized micelles of block copolymers of methoxy poly(ethylene glycol)-poly(ε-caprolactone)-graft-2-hydroxyethyl cellulose for doxorubicin delivery 29

4 Synthesis and characterization of PEG-PCL-PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer 22

5 Overcoming multidrug resistance of breast cancer cells by the micellar doxorubicin nanoparticles of mPEG-PCL-graft-cellulose 19

6 Curcumin-Loaded Chitosan/Gelatin Composite Sponge for Wound Healing Application 18

7 Molecular Targeting of Liposomal nano-particles to Lymphatic System 17

8 Recent Development in Nano-sized Dosage Forms of Plant Alkaloid Camptothecin-Derived Drugs 15

9 Doxorubicin-loaded nanosized micelles of a star-shaped poly(ε-caprolactone)-polyphosphoester block copolymer for treatment of human breast cancer 15

10 Recent advances in pharmacokinetics of polymeric excipients used in nanosized anti-caprolactone) (PCL)cancer drugs 15

19

Future plans

Polymeric nanopartilce for drug delivery for cancer treatment

Biomaterial membrane

Nanomaterial for wastewater treatment

(Composition, form, size, shape)

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