(provided by candidate): ? The central aim of this K08 proposal is to develop a technology for disease-specific targeting of controlled release polymer systems using nucleic acid ligands (aptamers) as escort molecules. The targeting of controlled-release polymer systems is desirable especially when treating a condition such as cancer where it is important that a cytotoxic dose of the drug is delivered to cancer cells without killing the surrounding noncancerous tissue. To examine and demonstrate the feasibility of our approach, we propose to isolate Prostate Cancer (PCa)-specific aptamers for targeting of drug encapsulated nanoparticle-aptamer controlled release polymer delivery vehicles to PCa. Our research has 4 specific aims: 1) isolation of PCa-specific aptamers; 2) characterization of the target antigen that binds to each aptamer; 3) development of PCa drug delivery vehicles comprised of PCa-specific aptamers conjugated to controlled release polymer nanoparticles; and 4) evaluation of the resulting PCa-specific delivery vehicles in-vitro and in-vivo. We will use a novel screening method to isolate aptamers that bind to antigens expressed on PCa cells. The successful development of our methodology could result in isolating other disease-specific aptamers for virtually any disease as long as there is a differential expression of antigens between the diseased tissue and its normal tissue counterpart. Second, aptamers isolated as part of our strategy would be used as tools to purify their targets using ligand mediated protein purification which could result in the identification of novel disease-specific markers. Third, within the scope of this proposal, disease-specific aptamers would serve as escort molecules for delivering drugs to their respective diseased tissue. However, the utility of disease specific aptamers can extend far beyond our proposed application. For example, disease-specific aptamers will be valuable for generating future diagnostic and prognostic modalities. A conjugate of a disease-specific aptamers with an imaging contrast may be used for detection of a disease focus. Disease-specific aptamers could also be used for histological evaluation of pathologic tissue in a similar manner as antibodies for determining disease diagnosis and prognosis. Therefore, isolating disease-specific aptamers for use in targeted therapeutic and diagnostic applications has broad significance and may impact a myriad of important human diseases. ? ?

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Clinical Investigator Award (CIA) (K08)
Project #
Application #
Study Section
Special Emphasis Panel (ZEB1-OSR-B (O1))
Program Officer
Erim, Zeynep
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Lim, Jong-Min; Cai, Truong; Mandaric, Stefan et al. (2018) Drug loading augmentation in polymeric nanoparticles using a coaxial turbulent jet mixer: Yong investigator perspective. J Colloid Interface Sci 538:45-50
Lim, Jong-Min; Swami, Archana; Gilson, Laura M et al. (2014) Ultra-high throughput synthesis of nanoparticles with homogeneous size distribution using a coaxial turbulent jet mixer. ACS Nano 8:6056-65
Lim, Jong-Min; Bertrand, Nicolas; Valencia, Pedro M et al. (2014) Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D flow focusing towards in vivo study. Nanomedicine 10:401-9
Radovic-Moreno, Aleksandar F; Lu, Timothy K; Puscasu, Vlad A et al. (2012) Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano 6:4279-87
Graf, Nora; Bielenberg, Diane R; Kolishetti, Nagesh et al. (2012) ýý(V)ýý(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug. ACS Nano 6:4530-9
Xiao, Zeyu; Levy-Nissenbaum, Etgar; Alexis, Frank et al. (2012) Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection. ACS Nano 6:696-704
Xiao, Zeyu; Farokhzad, Omid C (2012) Aptamer-functionalized nanoparticles for medical applications: challenges and opportunities. ACS Nano 6:3670-6
Salvador-Morales, Carolina; Valencia, Pedro M; Thakkar, Anjali B et al. (2012) Recent developments in multifunctional hybrid nanoparticles: opportunities and challenges in cancer therapy. Front Biosci (Elite Ed) 4:529-45
Wang, Andrew Z; Langer, Robert; Farokhzad, Omid C (2012) Nanoparticle delivery of cancer drugs. Annu Rev Med 63:185-98
Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M et al. (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41:2971-3010

Showing the most recent 10 out of 50 publications