RESEARCH

Welcome to the Bioengineering & Nanomedicine (BENMD) Program at the Gordon Center for Medical Imaging of Massachusetts General Hospital and Harvard Medical School. Our mission is to improve the diagnosis and treatment of human diseases by making advanced imaging technology available to patients and researchers worldwide.

Our current research focuses on the development of new theranostic agents for diagnosis, staging, and treatment of human diseases, especially cancer and inflammatory diseases, using state-of-the-art molecular imaging technology. To achieve this goal, we have assembled a multi-disciplinary team of researchers including chemists, engineers, biologists, physicists, and surgeons. This is a very unique environment, where experts from diverse fields work together in an effort to achieve the same goal. At the Gordon Center for Medical Imaging, we are attempting to combine our optical imaging technology with nuclear medicine, which will provide anatomic and functional imaging and treatment of human diseases. With the combination of our image-guided surgery system and targeted contrast agents, we have the potential to change the face of human cancer surgery and treatment.

Our focus is on five areas of development:

  1. Bioimaging devices to provide real-time functional intraoperative imaging,
  2. Targeted contrast agents for tissue- and organ-specific diagnosis and treatment,
  3. Image-guided drug delivery systems for image-guided drug delivery and therapy,
  4. Immuno-oncology imaging to investigate the mechanisms of action in immunology and oncology,
  5. Clinical translation of tissue engineering and image-guided surgery to help patients in need.

Bioimaging devices: Although many of our research interests are multi-modal, including MRI, SPECT, and PET, our primary focus is near-infrared fluorescence imaging and its clinical applications. Near-infrared light is invisible to the human eye, but is capable of penetrating relatively deeply into living tissue. Our BENMD Program took the lead in imaging system development and invented multispectral and multiscale near-infrared fluorescence imaging systems that permit anatomy and function to be visualized simultaneously in real-time, with high sensitivity and no moving parts. These systems provide complete image guidance to surgeons during tumor resection and other surgeries in which a tissue target must be detected, assessed, or resected.

Targeted contrast agents: Contrast for our imaging system is provided by exogenously introduced near-infrared fluorophores. The BENMD program has taken a lead role in this field as well. To date we have developed robust methods for synthesizing targeted contrast agents based on near-infrared fluorophores, as well as biocompatible polymeric nanoparticles. Armed with real-time imaging systems, the structure-inherent targeting strategy can be used for image-guided surgery and surgical interventions by specifically visualizing target tissue with high optical properties and by avoiding nonspecific uptake in normal background tissues. We can achieve high affinity to the target by controlling the innate biodistribution of contrast agents through modulating the overall molecular characteristics of the pharmacophore and making selective modifications in distinct regions.

Note: Structure-inherent targeting is a novel concept which first appeared in Nature Medicine in 2015 to develop tissue-specific targeted small molecules for targeting and imaging, as well as diagnosis and treatment of human diseases.

Drug delivery systems: Armed with the ability to a priori engineer targeted contrast agents, we are interested in developing ideal theranostic nanocarriers that exhibit extended systemic circulation, rapid distribution, and renal excretion from the body after complete targeting of regions of interest, while also avoiding nonspecific uptake by the immune system. The renal clearable zwitterionic nanocarriers (a.k.a., H-Dots) are composed of a biocompatible polymer backbone for biodistribution and clearance, near-infrared fluorophores for bioimaging, and cyclodextrins for delivery of many kinds of small molecule drugs (e.g., antivirals and anticancer drugs).

Immuno-oncology imaging: Our BENMD program is also investigating immuno-oncology using nanotherapeutics and near-infrared imaging technology. Our mission is to create a novel medical imaging methodology and advance our understanding of immunology and immunotherapy. Our central focus has been to develop a new imaging technology to dissect the immune response in the context of cancer and allergic and infectious diseases with an ultimate goal of translating this knowledge to the clinical practice. For example, our group successfully established (1) near-infrared imaging technology of immune components including vaccines and exosomes to improve immunotherapy and (2) molecular imaging of cancer signaling to develop a novel targeted cancer therapy. We are also working to establish safe, effective, simple, and affordable immunotherapy for infectious diseases, allergy, autoimmune diseases, and cancer using our near-infrared laser technology.

Clinical translation: Our final goal is to translate our imaging technology to the clinic. Based on the first principles of chemistry, engineering, and biology, we have defined the relationship among the key independent variables of targeted fluorophores that dictate biodistribution and tissue-specific targeting in various animal models including mice, rats, and pigs. The specificity and sensitivity of targeted fluorophores can be achieved by specifically visualizing target tissue with Superior optical properties and by avoiding nonspecific uptake in normal background tissues. Furthermore, we produced high-purity heptamethine indocyanines for large animal and human studies using cGMP-compatible processes (10 g scale; ≈ 1,000 patient doses) through facile and efficient solvent purification, without the need for column chromatography. We are currently attempting simultaneous targeting of cancerous tissue and vasculature/nerve; bone and cartilage; cartilage/bone and vessel/nerve using dual-channel intraoperative imaging, which lays the foundation for clinical translation to image-guided surgery and longitudinal/noninvasive imaging of tissue constructs.

Together, our research has the potential to greatly impact the development of tissue-specific theranostic agents for human diseases. When combined with the FIAT-L™ image-guided surgery system, we can provide highly sensitive and specific images of regions of interest in real time and can elucidate mechanisms of action and molecular characteristics using the same targeted contrast agents under the mesoscale imaging system.