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Nanobiotechnology 2018

Page 61

Nano Research & Applications

ISSN: 2471-9838

E u r o S c i C o n C o n f e r e n c e o n

Nanotech & Nanobiotechnology

J u l y 1 2 - 1 3 , 2 0 1 8

P a r i s , F r a n c e

B

reast cancer is a leading cause of mortality in females worldwide. Tamoxifen continues to be the standard endocrine therapy,

which requires metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations

of CYP activity at the tumour remain major bottlenecks for the effcient treatment, causing severe side-effects. Combination

nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting

the therapeutic response. The principle of combination therapy in cancer is to use approaches that work by different mechanisms

of action. Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven

enzyme prodrug therapy and photodynamic therapy. The estrogen receptors (ER) are the major role players in the initiation and

progression of breast cancer and represent a potential site for directing receptor-mediated cellular uptake. Thus, in our approach

we have functionalized biocatalytic P22 with the well-known photosensitizer, protoporphyrin IX (PpIX) and the estradiol derivative

for achieving targeted inhibition of ER+ breast tumour cells. The fnal nanoparticles, P22CYP-PpIX-PEG(EST) are characterized by

TEM, DLS, zeta potential and photo-physical analysis. These functionalized nanoparticles are recognized by and internalized into

ER

+

breast tumour cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS)

upon UV

365nm

irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity

in

vitro

, leading to a strong inhibition of tumour cells, which may allow the reduced toxicity owing to the lower drug concentration,

and may overcome the tumour reoccurrence limitation. Thus, the targeted combinatory treatment using multifunctionalized

biocatalytic P22 represents the effective nanotherapeutics for ER

+

breast cancer.

chauhankanchan4@gmail.com

Multifunctionalized biocatalytic P22 nanoreactor

for combinatory treatment of ER+ breast cancer

Kanchan Chauhan, Juan M Hernandez-Meza, Ana G Rodriguez-

Hernandez, Karla Juarez-Moreno, Prakhar Sengar and Rafael

Vazquez-Duhalt

Center for Nanoscience and Nanotechnology-UNAM, Mexico

Nano Res Appl 2018, Volume 4

DOI: 10.21767/2471-9838-C2-012