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Volume 4
Nano Research & Applications
ISSN: 2471-9838
Page 28
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
Patrick J Sinko et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-014
Nanotechnology approaches for intensifying localized combination therapy for precision treatment
of early stage breast cancer
Patrick J Sinko, Firas Al Zubaydi, In Heon Lee, Zoltan Szekely, Jennifer Holloway, Dayuan Gao
and
Hatem Sabaawy
1
Rutgers The State University of New Jersey, USA
2
Rutgers Cancer Institute of New Jersey, USA
D
uctal carcinoma
in situ
(DCIS) is a noninvasive breast cancer (BC) with possible microinvasions into the breast stroma.
DCIS accounts for more than 16% of new BC diagnoses in women. DCIS progresses to Invasive Ductal Carcinoma
(IDC) over time in 39-53% of patients, if left untreated. The vast majority of BC cases originate in the mammary duct. In
this presentation, a nanoscale delivery system will be described that utilizes transpapillary delivery to achieve molecularly
targeted, pathway-specific therapy in cancerous areas of the mammary duct. Our preliminary results with a nanosuspension
of ciclopirox (CPX) in an orthotopic model of BC established the concept that sustained ductal exposure could completely
suppress BC occurrence
in vivo
. For these studies polymeric NPs (nanoparticles) as well as lipid-polymer hybrid (LPH) NPs
were the primary delivery vehicles. In order to achieve sustained precision treatment, HER2, transferrin receptor and/or EGFR
were targeted using peptide ligands covalently bound to the surface of NPs. Ligand surface densities of 5% and 10% were
evaluated and it was found that surface functionalized NPs enhanced binding and uptake into target cells. Cytoxicity was
significantly increased with EGFR or TfR targeted NPs as compared to CPX alone or non functionalized CPX-loaded NPs. A
synergistic effect was observed when CPX was administered with gedatolisib, a PI3K/Akt/mTOR inhibitor resulting in a dose
reduction index of ~6. In addition, the treatments were effective not only in BC cells but also cancer stem-like cells. Our efforts
in addition to describing these studies and results, the engineering of the NPs to enhance ductal retention and specificity will
also be described.
Recent Publications
1. Gu Z et al. (2018) The effect of size and polymer architecture of doxroubicin-poly(ethylene) glycol conjugate
nanocarries on breast duct retention, potency and toxicity. European Journal of Pharmaceutical Sciences. 121:118-
125. Doi 10.1016/j.ejps.2018.04.033.
2. Lee I H et al. (2018) Design and evaluation of a CXCR4 targeting peptide 4DV3 as an HIV entry inhibitor and a ligand
for targeted drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. pii: S0939-6411(18)30013-
30014. Doi: 10.1016/j.ejpb.2018.06.004.
3. Singh Y D et al. (2012) Influence of molecular size on the retention of polymeric nanocarrier diagnostic agents in
breast ducts. Pharmaceutical Research. 29(9):2377-2388. Doi:10.1007/s11095-012-0763-z.
4. Singh Y D et al. (2011) Noninvasive detection of passively targeted poly(ethylene glycol) nanocarriers in tumors.
Molecular Pharmaceutics. 9(1):144-155. Doi:10.1021/mp2003913.
Biography
Patrick J Sinko is a Pharmacist (BS, Rutgers 1982) and a Pharmaceutical Scientist (PhD, University of Michigan 1988). He joined Rutgers, The State University of
New Jersey in 1991 and rose through the academic ranks where he is currently a Distinguished Professor (II) and the Parke-Davis Endowed Chair in Pharmaceutics
and Drug Delivery in the Ernest Mario School of Pharmacy. He is the Principal Investigator of an active research laboratory that focuses on biopharmaceutics,
pharmaceutical formulations and molecular-, nano- and micro-scale drug delivery with specific applications to the treatment or prevention of HIV/AIDS, breast, brain
and lung cancer, chemical terrorism countermeasures. He has received prestigious National Institutes of Health FIRST and MERIT awards and his lab has been
continuously funded by the NIH for over 25 years.
sinko@rutgers.edu