Development and High Throughput Screening of Targeted Anticancer Nanomedicines This proposal belongs to the area of research focus """"""""Multifunctional nano-therapeutics and post-therapy monitoring tools"""""""". As an integral part of our CCNE project, it aims to pave the way to clinical trials of targeted nanomedicines by dramatically accelerating their screening at early steps of development by adapting the principals of combinatorial parallel synthesis of multiple liposomal nanostructures. In the proposed concept, the advanced pharmaceutical nanocarriers - PEGylated """"""""stealth"""""""" liposomes encapsulating one of the four representative drugs (doxorubicin, paclitaxel, gemcitabine or vincristin) are targeted to the pancreatic and lung tumor cells by cancer cell-specific phage fusion proteins. The phages will be affinity selected from landscape phage libraries by their ability to bind very specifically cancer cells and/or penetrate into the cells. The selected tumor-specific phages will be amplified, stripped and converted into the drug-loaded vesicles, in which spontaneously inserted phage proteins span the lipid bilayer displaying the tumor-binding peptides on the surface of the vesicles. To demonstrate the power of the new approach, up to 100 phages demonstrating highest selectivity and affinity towards the target cancer cells will be combined with four """"""""parental"""""""" liposomes containing different anticancer drugs and tested in high throughput format. The most efficient compositions of targeting proteins and drugs will be further optimized, prepared in large scale in GLP/GMP conditions at the Center's Scaling up and Manufacturing Core and studied for antitumor activity in vivo in mouse models at the animal facilities of Northeastern University. In contrast to the traditional rational design of anticancer nanomedicines, the proposed combinatorial approach does not require preliminary identification of cancer-specific cellular receptors, development of peptide or antibody ligands to these receptors and idiosyncratic techniques for their conjugation to the drug loaded nanoparticles. We hypothesize that proposed combinatorial approach to the development of targeted liposomal nanomedicines will lead to significant enhancement of their screening throughput by as much as 1000-fold, and result in dramatic acceleration of translational process.

Public Health Relevance

This proposal addresses a critical barrier to progress in the development of targeted anticancer nanomedicines, which is currently grounds on rational design and individual testing. It comprises a first attempt to accelerate the anticancer screening of nanomedicines by adapting the principals of combinatorial parallel synthesis of multiple liposomal drug structures and advanced phage nanobiotechnology.developed n Pi's groun

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northeastern University
United States
Zip Code
Jhaveri, Aditi; Deshpande, Pranali; Pattni, Bhushan et al. (2018) Transferrin-targeted, resveratrol-loaded liposomes for the treatment of glioblastoma. J Control Release 277:89-101
Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan et al. (2018) Phage-derived protein-mediated targeted chemotherapy of pancreatic cancer. J Drug Target 26:505-515
Kumar, Gaurav; Goldberg, S Nahum; Gourevitch, Svetlana et al. (2018) Targeting STAT3 to Suppress Systemic Pro-Oncogenic Effects from Hepatic Radiofrequency Ablation. Radiology 286:524-536
Upponi, Jaydev R; Jerajani, Kaushal; Nagesha, Dattatri K et al. (2018) Polymeric micelles: Theranostic co-delivery system for poorly water-soluble drugs and contrast agents. Biomaterials 170:26-36
Petrenko, Valery A; Gillespie, James W (2017) Paradigm shift in bacteriophage-mediated delivery of anticancer drugs: from targeted 'magic bullets' to self-navigated 'magic missiles'. Expert Opin Drug Deliv 14:373-384
van de Ven, Anne L; Tangutoori, Shifalika; Baldwin, Paige et al. (2017) Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation. Mol Cancer Ther 16:1279-1289
Pattni, Bhushan S; Jhaveri, Aditi; Dutta, Ivy et al. (2017) Targeting energy metabolism of cancer cells: Combined administration of NCL-240 and 2-DG. Int J Pharm 532:149-156
Su, Mei-Ju; Aldawsari, Hibah; Amiji, Mansoor (2016) Pancreatic Cancer Cell Exosome-Mediated Macrophage Reprogramming and the Role of MicroRNAs 155 and 125b2 Transfection using Nanoparticle Delivery Systems. Sci Rep 6:30110
Sriraman, Shravan Kumar; Pan, Jiayi; Sarisozen, Can et al. (2016) Enhanced Cytotoxicity of Folic Acid-Targeted Liposomes Co-Loaded with C6 Ceramide and Doxorubicin: In Vitro Evaluation on HeLa, A2780-ADR, and H69-AR Cells. Mol Pharm 13:428-37
Gillespie, James W; Wei, Lixia; Petrenko, Valery A (2016) Selection of Lung Cancer-Specific Landscape Phage for Targeted Drug Delivery. Comb Chem High Throughput Screen 19:412-22

Showing the most recent 10 out of 86 publications