Nanotechnology Meets Cancer
4:00PM Nanodevices For
Cancer Therapy
Shiladitya Sengupta, PhD, Assistant Professor of Medicine and
Health Sciences and Technology, Harvard Medical School, Brigham & Women's
Hospital, Massachusetts Institute of Technology, shiladit@mit.edu
Moderator: Jose Miguel Trevejo, MD, PhD,
Senior Scientist, Biomedical Engineering Group, The Charles Stark Draper
Laboratory, Department of Infectious Disease, Beth Israel Deaconess
Medical Center,
The idea of
building structures atom by atom has been around for decades, but only recently
have researchers gained the tools to make nanotechnology a reality. In medicine, there are many opportunities for
nanotechnology to improve the care that patients receive. Nanodevices are already being developed for
use as biosensors, as part of imaging systems, and as drug delivery vehicles. All three of these functions promise to help
improve cancer therapy.
Angiogenesis,
or the formation of new blood vessels, plays a major role in the development of
a tumor. After a tumor has grown to
about the size of a cubic millimeter, its core becomes hypoxic, and it begins
to release growth factors to recruit new blood vessels that will supply it with
oxygen. Inhibiting angiogenesis has been
investigated as a means of preventing tumor growth but has not proven to be
fully successful, for tumor cells cut off from the blood supply can eventually
develop “reactive resistance” to hypoxia.
These resistant cancer cells could be killed by chemotherapeutic drugs,
but once the vasculature to the tumor has been cut off, there is no way for
chemotherapy to be delivered.
Nanotechnology offers a way to deliver chemotherapeutic drugs and
anti-angiogenic drugs in the same vehicle so that as the blood supply is shut
off, chemotherapy is present to prevent any hypoxia-resistant cells from
proliferating.
The lab of
Shiladitya Sengupta is in the process of developing nanocells capable of
delivering both types of drugs. Each
nanocell is between 120 and 200 μm in diameter and can be thought of as “a
balloon within a balloon.” Inside each
nanocell is a chemotherapeutic drug covalently bound to a polymer, and on the
surface of each cell is a lipid coat containing an anti-angiogenic drug. The technology makes use of the fact that a
tumor’s blood vessels have pores 600 μm in diameter and are much leakier
than normal blood vessels, which have pores only around 50 μm in
diameter. The nanocells circulate in the
blood, and because of their size, they leak out of blood vessels only in
tumors. Once there, the nanocells are
degraded by enzymes produced by the tumor.
Work remains to be done to win clinical approval for the technology, but
results from Sengupta’s lab indicate that the nanocells are more effective and
less toxic than traditional chemotherapy.
5:00PM Tumor Microenvironment in Cancer
Progression and Metastasis
Raghu Kalluri,
PhD, Professor of Medicine, Harvard Medical School, Department of Biological
Chemistry and Molecular Pharmacology, Harvard-MIT Division of Health Sciences
and Technology; Chief, Division of Matrix Biology, Department of Medicine, Beth
Israel Deaconess Medical Center, rkalluri@bidmc.harvard.edu
Moderator: Jeffrey Borenstein, PhD, Director,
Biomedical Engineering Center; Distinguished Member of the Technical Staff,
Charles Stark Draper Laboratory; Program Leader for Biomaterials and Tissue
Engineering and Draper Laboratory Site Miner, CIMIT, jborenstein@draper.com
Around
twenty million people worldwide are diagnosed with cancer every year,
and eight to nine million die. Cancer is
much more prevalent, however, than even these numbers suggest. Many people have cancerous lesions in their
bodies but do not become ill and do not seek medical attention. Based on autopsy studies, for example, it
seems that everyone over the age of fifty has small, dormant carcinomas in the
thyroid, although less than one percent will present with cancer in the clinic. Latent carcinomas in the prostate or breast all
also commonly observed. These lesions
have many of the features of invasive cancer but do not exhibit invasive
behavior. It seems that the body’s
natural defenses, not just the genetic instability of the cancerous cells
themselves, determines to what extent a tumor proliferates.
Genetic
defects in cancerous cells are not responsible for all the observed variation
in their growth rates. The host
environment also plays a role. One way
in which systemic factors might affect cancer proliferation involves the
“angiogenic switch concept.”
Angiogenesis can promote tumor growth, yet to some extent, angiogenesis
is controlled by regulators that circulate throughout the entire body. Different people will have different
background levels of angiogenic regulators, so some people’s bodies will
naturally lie closer to the tipping point where angiogenesis is turned
“on.” Thus, according to this
hypothesis, tumors will be more likely to prompt angiogenesis in some people
than in others not because of differences amongst the tumors but because of
background differences amongst the people.
In mice with cancer, for example, the presence or absence of certain
genes responsible for inhibiting endothelial proliferation significantly
affects survival.
Tumors are
not entirely composed of cancerous cells, and researchers still do not know
whether non-cancerous cells in a tumor have been recruited to help it grow or
whether they are there to contain it.
Fibroblasts, in particular, fulfill mysterious functions. These cells exhibit marked
heterogeneity. Some inhibit metastasis
but not proliferation while others have unknown effects. The immune system also seems to play an
important role in holding back the spread of cancerous cells. These observations suggest that when
considering cancer, one should think about the phase during which there is
cancer without disease. In treating
patients, perhaps the goal should be to prolong this phase for as long as
possible. For patients with cancer,
perhaps therapy should be focused on restoring the body’s natural checks on
proliferation and metastasis, in addition to merely obliterating the cancer and
hoping it doesn’t come back.
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