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Volume 4

Nano Research & Applications

ISSN: 2471-9838

Page 50

JOINT EVENT

August 16-18, 2018 | Dublin, Ireland

&

12

th

Edition of International Conference on

Nanopharmaceutics and Advanced Drug Delivery

25

th

Nano Congress for

Future Advancements

Nano Congress 2018

&

Nano Drug Delivery 2018

August 16-18, 2018

Immunoliposomes containing simvastatin, targeted towards EGFR, as potential therapeutic for

treatment of EGFR-dependent breast cancer tumors

Lucyna Matusewicz

and

Aleksander F Sikorski

University of Wroclaw, Poland

Introduction:

Epidermal Growth Factor Receptor (EGFR) was shown to be highly expressed in many types of human

cancer, among others, in breast cancers. EGFR overexpression correlates with advanced stage of the disease and with poor

response to chemotherapy. One of the promising strategy for the treatment of EGFR-dependent tumors is to inhibit signal

transduction from EGFR via disruption of cholesterol rich membrane rafts. We assume that targeted delivery of simvastatin, a

popular cholesterol-depleting drug widely prescribed in the treatment of cardiovascular diseases, will specifically disorganize

membrane rafts and therefore disturb the EGFR dependent signalling pathways that usually promote cell proliferation and

metastases. Statins were shown to exert antitumor effects in high doses, but those may lead to serious side effects. Therefore,

the main purpose of this work is to obtain targeted, long circulating liposomes with simvastatin and to test their anticancer

activity both

in vitro

and

in vivo

.

Methodology:

Liposomes were prepared via lipid film hydration method and modified by attachment of antibodies specific to

EGFR. Stability, selectivity and toxicity of targeted liposomes were analyzed both

in vitro

and

in vivo

. The level of activation

of selected kinases involved in transduction of signals stimulated via EGF in cells treated by immunoliposomal statin was

examined. Moreover, changes in plasma membrane order of cells exposed to liposomal simvastatin were examined using FLIM

(Fluorescence-lifetime imaging) method.

Findings:

Designed immunoliposomes were stable over 6 months, selective towards EGFR overexpressing cells and showed

antitumor efficacy both

in vitro

and

in vivo

. Inhibition of signaling pathway involving Akt in cells treatedwith immunoliposomal

simvastatin and disruption in plasma membrane order were observed.

Conclusions:

Presented immunoliposomal formulation of simvastatin seems reasonable solution of a specific delivery of high

doses of this drug into tumor cells and a candidate of further evaluation for efficacy either in monotherapy or in combination

in anticancer therapies in the future.

Recent Publications

1. Matusewicz L et al. (2015) The effect of statins on cancer cells-review. Tumour Biol. 36(7):4889-4904.

2. Luput L et al. (2018)

In vivo

double targeting of C26 colon carcinoma cells and microenvironmental protumor

processes using liposomal simvastatin. J. Cancer. 9(2):440-449.

3. Alupei M C et al. (2015) Liposomal simvastatin inhibits tumor growth via targeting tumor-associated macrophages-

mediated oxidative stress. Cancer Lett. 356(2 Pt B):946-952.

4. Coimbra M et al. (2010) Liposomal pravastatin inhibits tumor growth by targeting cancer-related inflammation. J.

Control Release. 148(3):303-310.

5. Kutty R V and Feng S S (2013) Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for

treatment of triple negative breast cancers. Biomaterials. 34(38):10160-10171.

Biography

Lucyna Matusewicz graduated with MSc in Biotechnology in 2012. She is currently a PhD student at the University of Wroclaw, Poland. She started her PhD project

and for almost 6 years has been focusing mainly on drug delivery systems in anticancer therapy.

matusewicz.lucyna@gmail.com

Lucyna Matusewicz et al., Nano Res Appl 2018, Volume 4

DOI: 10.21767/2471-9838-C3-014