Detection of reliable markers of therapy response and drug resistance remains a major clinical challenge in ovarian cancer. This is particularly true for a series of nanotherapeutics entering the clinical arena. One little explored opportunity lies in the analysis of exosomes, 50-200 nm sized vesicles continuously shed into the circulation. Importantly such tumor derived exosomes are abundant (1011 vesicles/ml of peripheral blood in cancer patients), are fairly stable over time and contain proteins reflective of those found in parent tumors. A current major challenge and opportunity is the development of methods for rapidly determining the abundance and composition of cMVs from clinical samples. We have recently developed a highly sensitive, nanotechnology-based, point-of-care diagnostic method termed nPLEX (nano Plasmonic Exosome) which comprises periodic nanohole arrays fabricated in an opaque gold film for transmission plasmon imaging (Nat Biotechnol 2014;32, 490-5). We have shown that i) such analyses are exquisitely sensitive, ii) allow profiling of dozens of proteins on and inside exosomes thus allowing cell of origin studies and iii) that nPLEX analysis allows sophisticated therapy assessment. The goal of this application is to advance the nPLEX technology by i) expanding it to allow parallel profiling of protein and RNA, ii) validating it as a therapeutic read-out of nanoparticle therapeutics in mouse models and in the clinic. We hypothesize that the approach will be more sensitive and comprehensive in exosomal analysis than is currently possible and allow treatment evaluation. The proposed integrated profiling method has the potential to transform nano therapeutic trials, cancer research and clinical practice. It will enable objective therapeutic read-outs, events that occur before conventional clinical metrics. It will facilitate extensive profiling of exosome in paucicellular clinical specimens, significantly reduce costs, and can be easily combined with other downstream analyses.

Public Health Relevance

We propose to further develop a new analysis technique to study key cancer cell proteins and mRNA in exosomes, small vesicles shed from cancer cells. The method not only allows much more extensive and robust profiling than what is currently possible but uses less material obviating the need for more invasive core biopsies, is cost effective, scalable and samples are not destroyed during the analytical process. The proposed profiling method has the potential to transform nano-therapy cancer trials as it provides broad, quantitative readouts.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA204019-02
Application #
9297249
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Sorg, Brian S
Project Start
2016-06-15
Project End
2021-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$389,111
Indirect Cost
$160,361
Name
Massachusetts General Hospital
Department
Type
Independent Hospitals
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Park, Yong Il; Kim, Eunha; Huang, Chen-Han et al. (2017) Facile Coating Strategy to Functionalize Inorganic Nanoparticles for Biosensing. Bioconjug Chem 28:33-37
Hong, Seonki; Park, Ki Soo; Weissleder, Ralph et al. (2017) Facile silicification of plastic surface for bioassays. Chem Commun (Camb) 53:2134-2137
Min, Changwook; Park, Jongmin; Mun, Jae Kyoung et al. (2017) Integrated microHall magnetometer to measure the magnetic properties of nanoparticles. Lab Chip 17:4000-4007
Im, Hyungsoon; Lee, Kyungheon; Weissleder, Ralph et al. (2017) Novel nanosensing technologies for exosome detection and profiling. Lab Chip 17:2892-2898
Im, Hyungsoon; Park, Yong Il; Pathania, Divya et al. (2016) Digital diffraction detection of protein markers for avian influenza. Lab Chip 16:1340-5
Pucci, Ferdinando; Garris, Christopher; Lai, Charles P et al. (2016) SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 352:242-6
Cho, Choi-Fong; Lee, Kyungheon; Speranza, Maria-Carmela et al. (2016) Design of a Microfluidic Chip for Magnetic-Activated Sorting of One-Bead-One-Compound Libraries. ACS Comb Sci 18:271-8
Pfirschke, Christina; Engblom, Camilla; Rickelt, Steffen et al. (2016) Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity 44:343-54
Park, Ki Soo; Chung, Hyun Jung; Khanam, Farhana et al. (2016) A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever. Sci Rep 6:32878
Jeong, Sangmoo; Park, Jongmin; Pathania, Divya et al. (2016) Integrated Magneto-Electrochemical Sensor for Exosome Analysis. ACS Nano 10:1802-9

Showing the most recent 10 out of 13 publications