Using Nanoparticles to treat Skin Cancer

Transcript

00:00 --> 00:03Funding for Yale Cancer Answers is provided
00:03 --> 00:07by Smilow Cancer Hospital and AstraZeneca.
00:07 --> 00:09Welcome to Yale Cancer Answers with
00:09 --> 00:12your host doctor Anees Chagpar.
00:12 --> 00:14Yale Cancer Answers features the
00:14 --> 00:16latest information on cancer care by
00:16 --> 00:18welcoming oncologists and specialists
00:18 --> 00:20who are on the forefront of the
00:20 --> 00:22battle to fight cancer. This week,
00:22 --> 00:25it's a conversation about the use of
00:25 --> 00:27nanoparticles to treat skin cancer with
00:27 --> 00:29doctors Michael Girardi and W. Mark Salzman.
00:29 --> 00:32Doctor Girardi is a professor of
00:32 --> 00:34dermatology and Doctor Saltzman is a
00:34 --> 00:35professor of biomedical engineering,
00:35 --> 00:37Cellular and Molecular Physiology
00:37 --> 00:39and of Chemical Engineering at
00:39 --> 00:40the Yale School of Medicine,
00:40 --> 00:42where Doctor Chagpar is a
00:42 --> 00:44professor of surgical oncology.
00:45 --> 00:47So maybe we'll start off by having
00:47 --> 00:50both of you tell us a little bit about
00:50 --> 00:52yourselves and what you do.
00:52 --> 00:55Mike, maybe I'll start with you.
00:55 --> 00:57Sure, I run a research laboratory
00:57 --> 00:59with a big focus on skin cancer
00:59 --> 01:02development and strategies to try to
01:02 --> 01:04prevent skin cancer formation and to treat it.
01:04 --> 01:06And how about you, Mark?
01:06 --> 01:09I'm a professor in the
01:09 --> 01:10Department of Biomedical Engineering.
01:10 --> 01:12My training is in chemical engineering,
01:12 --> 01:15but for my research career and my
01:15 --> 01:16teaching career I've mainly
01:16 --> 01:19focused on how to apply principles
01:19 --> 01:20from chemical engineering to
01:20 --> 01:22make new products for medicine.
01:22 --> 01:25This is such an
01:25 --> 01:27unusual marriage and something
01:27 --> 01:29that I love about academia is that
01:29 --> 01:32we can take disciplines that are
01:32 --> 01:34truly disperate on the surface
01:34 --> 01:36and make them collide and have
01:36 --> 01:38really fascinating things happen.
01:40 --> 01:43Mike, tell me a little bit more about
01:43 --> 01:46how your research evolved and
01:46 --> 01:48how you got to meet Mark?
01:48 --> 01:51You know we have a really rich
01:51 --> 01:54environment for exchange of ideas and just
01:54 --> 01:57a tremendous breadth of faculty that is
01:57 --> 02:00very welcoming to folks getting together.
02:00 --> 02:01Discussing how different perspectives
02:01 --> 02:04and takes on research can be combined.
02:04 --> 02:07Mark and I have had a
02:07 --> 02:10chance to see each other at various
02:10 --> 02:11meetings and conferences here
02:11 --> 02:14on campus and to
02:14 --> 02:16have discussions time to time
02:16 --> 02:18over the years after these meetings
02:19 --> 02:22and then we really hit it off on Mark's
02:22 --> 02:24technology of using nanoparticles
02:24 --> 02:27to deliver anti tumor agents.
02:28 --> 02:30And a thought bomb went off in my
02:30 --> 02:33head regarding all the potential
02:33 --> 02:36applications in the skin which is
02:36 --> 02:38so accessible and such a burden on
02:38 --> 02:41our society in terms of the
02:41 --> 02:45number of skin cancers and the
02:45 --> 02:47challenges in controlling these and treating them.
02:48 --> 02:52And so I reached out to Mark after one
02:52 --> 02:55of his talks and he was very receptive.
02:55 --> 02:58We had a wonderful meeting and
02:58 --> 03:00brainstorming session and that was
03:00 --> 03:02several years ago and we've really
03:02 --> 03:05grown with our possibilities and directions
03:06 --> 03:08research-wise in putting
03:08 --> 03:09our heads together.
03:09 --> 03:12Mark tell us a little bit more
03:12 --> 03:16about your research and this drug
03:16 --> 03:19delivery mechanism that you have and
03:19 --> 03:22the talk that spurred everything on?
03:23 --> 03:25I'll start back almost 30 years ago when I first
03:28 --> 03:30got interested in this field,
03:30 --> 03:32we had discovered that
03:32 --> 03:34there were some polymers,
03:34 --> 03:35some polymer materials,
03:35 --> 03:38plastics that one could implant in the
03:38 --> 03:42skin or put in contact with human tissues,
03:42 --> 03:44and they're very inert.
03:44 --> 03:47And the key discovery was that you could
03:47 --> 03:50combine these materials with drug molecules.
03:50 --> 03:52So that you could make such things
03:52 --> 03:54like implants that you could
03:54 --> 03:56place in contact with tissues or
03:56 --> 03:58implant into tissues and they would
03:58 --> 04:00slowly release the drug molecules
04:00 --> 04:02that you had embedded into them,
04:02 --> 04:05and so that really started me on a
04:05 --> 04:07path to thinking about how you could
04:07 --> 04:10both expand the range of materials
04:10 --> 04:12that you could use in this fashion,
04:12 --> 04:13and more importantly,
04:13 --> 04:16how you could marry this technology
04:16 --> 04:17to treat different diseases.
04:17 --> 04:20And we really focused a lot on cancer
04:20 --> 04:22because of the potential to create
04:22 --> 04:25drug delivery systems that would be
04:25 --> 04:27more effective at treating cancer.
04:27 --> 04:30But at the same time would be safer
04:30 --> 04:34and we could use the materials to sort
04:34 --> 04:38of focus the drug action on the tumor
04:38 --> 04:41cells rather than on normal tissue.
04:41 --> 04:44And I think the possibilities for this
04:44 --> 04:46really expanded about 15 years ago,
04:46 --> 04:48when we discovered you could
04:48 --> 04:49make not only implants,
04:49 --> 04:51but you could make tiny tiny
04:51 --> 04:53particles of these polymer
04:53 --> 04:55materials and anti cancer drugs.
04:55 --> 04:57So we call those nanoparticles because
04:57 --> 05:00their size is measured in the nanometers.
05:00 --> 05:01They're very small,
05:01 --> 05:05so the particles that Mike and I have been
05:05 --> 05:08using are about the same size as a virus.
05:08 --> 05:11So because they're so small you can
05:11 --> 05:13administer them easily in a
05:13 --> 05:14variety of different settings.
05:14 --> 05:17You can inject them easily through a needle,
05:17 --> 05:17for example.
05:17 --> 05:20Or you could suspend them in a
05:20 --> 05:22solution and infuse them or apply
05:22 --> 05:24them topically on the skin so that
05:24 --> 05:26that gives you a lot of possibilities
05:26 --> 05:29and thinking about how you're going
05:29 --> 05:31to match this delivery system to the
05:31 --> 05:33particular tumor that you're trying
05:33 --> 05:35to treat and the other thing about
05:35 --> 05:37being tiny tiny particles is that
05:37 --> 05:39they're much smaller than tumor cells,
05:39 --> 05:41and so they can actually enter into
05:41 --> 05:43tumor cells and once
05:43 --> 05:45they're in the tumor cell,
05:45 --> 05:47they'll start releasing slowly their drug,
05:47 --> 05:49and this allows the drug, the
05:49 --> 05:52source of the drug, to be released
05:52 --> 05:54very near its site of action,
05:54 --> 05:56which for anti-cancer drugs is
05:56 --> 05:59often in the nucleus of the cell,
05:59 --> 06:01and so this gives you another level
06:01 --> 06:03of control or design that you can
06:03 --> 06:06introduce into the the delivery system
06:06 --> 06:09in order to match them most
06:09 --> 06:10effectively to treat the particular
06:10 --> 06:12tumor that you're interested in.
06:12 --> 06:15And so Mike, tell us more about
06:15 --> 06:18the thought bomb that you had.
06:18 --> 06:20You know, it certainly sounds
06:20 --> 06:21like this technology that Mark
06:22 --> 06:23has is incredibly innovative,
06:23 --> 06:26but has so many possible applications.
06:26 --> 06:29So how did you really think about its
06:29 --> 06:32utility in terms of skin cancer?
06:32 --> 06:36I took a broad approach at first.
06:36 --> 06:38As to the potential applications in the
06:38 --> 06:41skin topical application, for example,
06:41 --> 06:43to improve sunscreen performance.
06:43 --> 06:46Injection into tumors to improve delivery
06:46 --> 06:48of anti tumor agents to skin cancers,
06:48 --> 06:51but also about the potential to stimulate
06:51 --> 06:53the immune system against cancer.
06:53 --> 06:55How these could facilitate
06:55 --> 06:56delivery of those agents.
06:56 --> 07:00Mark and I also talked about the various
07:00 --> 07:02inflammatory diseases of the skin and
07:02 --> 07:05how we might use agents that are anti
07:05 --> 07:07inflammatory and better deliver
07:07 --> 07:09those agents and increase their performance,
07:09 --> 07:11increase their safety so they're
07:11 --> 07:13not necessarily impacting the
07:13 --> 07:14overall immune system in a negative way.
07:16 --> 07:18and throughout the entire body,
07:18 --> 07:20so it's about local delivery.
07:20 --> 07:22It's about increasing drug
07:22 --> 07:24availability in terms of cancer.
07:24 --> 07:27We have a huge burden
07:27 --> 07:29with basal cell carcinoma.
07:29 --> 07:32These are a huge number of cancers
07:32 --> 07:35across the the world that outnumber all
07:35 --> 07:38cancers combined in their occurrence,
07:38 --> 07:41and often are treated by surgery or
07:41 --> 07:44multiple surgeries on the same patient.
07:44 --> 07:46An individual can develop many
07:46 --> 07:48of these over a lifetime if
07:48 --> 07:50they are fair skinned and
07:50 --> 07:52have a lot of sun exposure.
07:52 --> 07:54There is squamous cell carcinoma which
07:54 --> 07:56presents another set of problems.
07:56 --> 07:59They can be numerous as well,
07:59 --> 08:01but they can also have a small chance
08:01 --> 08:04of traveling throughout the body.
08:04 --> 08:07They tend to be deeper as well.
08:10 --> 08:13Melanoma not as common as basal
08:13 --> 08:15cell and squamous cell carcinoma.
08:15 --> 08:18But a whole other set of problems si that
08:18 --> 08:21this is a real killer of young people.
08:21 --> 08:22Melanoma is
08:22 --> 08:25something that has a very high risk
08:25 --> 08:27of metastasis after it obtains
08:27 --> 08:29a certain level of depth.
08:29 --> 08:30There are clear,
08:30 --> 08:32unmet needs in some patients who
08:32 --> 08:33have intermediate depth Melanoma
08:33 --> 08:35that has already metastasized
08:35 --> 08:37to regional lymph nodes.
08:37 --> 08:40And there are challenges in treating
08:40 --> 08:42these patients without necessarily
08:42 --> 08:44giving them something aggressive
08:44 --> 08:46and systemically delivered.
08:46 --> 08:48Chemotherapy to the entire body.
08:48 --> 08:51So all of these potential challenges
08:51 --> 08:55in the world of skin cancer
08:55 --> 08:58have areas that could be
08:58 --> 08:59potentially leveraged with this technology.
08:59 --> 09:02Mark and I have
09:02 --> 09:04been really trying to look at all
09:04 --> 09:06of the possibilities and begin
09:06 --> 09:08to develop research programs
09:08 --> 09:10and strategies to address them.
09:10 --> 09:13Mark, a couple
09:13 --> 09:15of things that struck me when
09:15 --> 09:18you were talking about this
09:18 --> 09:20technology, one is that these
09:20 --> 09:23nanoparticles are so small that they can
09:23 --> 09:26actually be engulfed by the tumor
09:26 --> 09:29cell and have a mechanism of action
09:29 --> 09:30at their nucleus, essentially,
09:30 --> 09:31really targeted therapy,
09:31 --> 09:34delivered to the source of the tumor.
09:34 --> 09:36But my question there is,
09:36 --> 09:38how targeted can it be?
09:38 --> 09:40I mean can you make these
09:40 --> 09:43nanoparticles such that the tumor cells
09:43 --> 09:45and only the tumor cells engulf them?
09:45 --> 09:47How does that work?
09:47 --> 09:48That's a great question and I think
09:51 --> 09:53there's several different aspects to that.
09:53 --> 09:56The one that we've been talking about
09:56 --> 09:59so far and a major
09:59 --> 10:01one that Mike and I have been
10:01 --> 10:02exploring is to
10:02 --> 10:04put the particles as close to
10:04 --> 10:06the tumor cells as possible.
10:06 --> 10:08To physically target them,
10:08 --> 10:10inject them into a tumor,
10:10 --> 10:11for example.
10:12 --> 10:14And that's possible with the skin cancers
10:14 --> 10:16that Mike is mentioning,
10:16 --> 10:18because they're so accessible,
10:18 --> 10:20they're on the surface of the skin,
10:20 --> 10:23at least some of them are
10:23 --> 10:25exclusively on the surface of the skin,
10:26 --> 10:29and dermatologists are very comfortable with
10:29 --> 10:30using needles to inject locally
10:30 --> 10:33in the skin and they're very
10:33 --> 10:34talented as well,
10:34 --> 10:36and so that makes a
10:36 --> 10:38reasonable form of targeting.
10:38 --> 10:40But you could also make it more
10:40 --> 10:42targeted and one possible way to
10:42 --> 10:45make it more targeted is to take
10:45 --> 10:46the nanoparticles and engineer
10:46 --> 10:48the surface properties of them.
10:48 --> 10:51And one of the aspects of the
10:51 --> 10:52technology that we've exploited
10:52 --> 10:55in many of the projects that we
10:55 --> 10:57worked on is to make the particles
10:57 --> 10:59themselves very sticky to proteins.
10:59 --> 11:01Or tumor cells that have a lot
11:01 --> 11:03of proteins on their surface.
11:03 --> 11:05And so when you inject these
11:05 --> 11:07sticky particles they will
11:07 --> 11:10tend to be taken up by whatever
11:10 --> 11:12cells are near the site where
11:12 --> 11:14you've placed them and this
11:14 --> 11:17allows the vast majority of the
11:17 --> 11:20particles to stay in a tumor if you
11:20 --> 11:22inject them right into the skin tumor,
11:22 --> 11:23for example.
11:23 --> 11:25And so that's one one way to
11:25 --> 11:27augment the targeting that local
11:27 --> 11:29delivery naturally provides you.
11:29 --> 11:31A second way would be to not just
11:31 --> 11:33use physical properties like
11:33 --> 11:35stickiness of particles to make
11:35 --> 11:37them attractive to tumor cells,
11:37 --> 11:39but to make them specifically
11:39 --> 11:40adhesive to tumor cells.
11:40 --> 11:41So in that case,
11:41 --> 11:44if you knew that there was
11:44 --> 11:47a protein on the tumor cell surface
11:47 --> 11:49that was expressed very abundantly in
11:49 --> 11:52the tumor cells and not in normal cells,
11:52 --> 11:54you could put some chemicals
11:54 --> 11:56that bind to that protein on the
11:56 --> 11:58surface of the nanoparticle.
11:58 --> 12:00So this might be an antibody.
12:00 --> 12:03Or an antibody fragment that
12:03 --> 12:06is specific for that protein that's
12:06 --> 12:08highly enriched on the tumor cell.
12:08 --> 12:11Then that gives you an additional
12:11 --> 12:12level of targeting.
12:12 --> 12:17And it's even possible to think about
12:17 --> 12:20administering those highly
12:20 --> 12:22targeted particles systemically and
12:22 --> 12:25and asking them to find the tumor
12:25 --> 12:27for you instead of you using the
12:27 --> 12:29needle to find the tumor yourself.
12:29 --> 12:33And that's been a very active area of
12:33 --> 12:37study over the past 10 to 15 years or so,
12:37 --> 12:40and it turns out to be
12:40 --> 12:42hard to achieve practically for
12:42 --> 12:44reasons that we could discuss.
12:44 --> 12:46But it's also a method of targeting.
12:46 --> 12:48I would like
12:48 --> 12:50to get into how exactly we target
12:50 --> 12:53things and what are the challenges
12:53 --> 12:55that are being faced in this
12:55 --> 12:56really exciting area, but first
12:56 --> 12:59we need to take a short break
12:59 --> 13:01for a medical minute, so please stay
13:01 --> 13:03tuned to learn more about nanoparticles
13:03 --> 13:06and skin tumors with my guests
13:06 --> 13:07Doctor Michael Girardi and
13:08 --> 13:09Doctor Mark Saltzman.
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14:21 --> 14:23Welcome back to Yale Cancer Answers.
14:23 --> 14:26This is Doctor Anees Chagpar
14:26 --> 14:29and I'm joined tonight by my guest doctor
14:29 --> 14:32Michael Girardi and Doctor Mark Saltzman.
14:32 --> 14:34We're talking about research looking
14:34 --> 14:37into using nanoparticles to treat
14:37 --> 14:39skin tumors and right before the
14:39 --> 14:42break we were talking about how these
14:42 --> 14:44nanoparticles are so small and how we
14:44 --> 14:47can try to make them really attack
14:47 --> 14:50tumor cells rather than normal cells.
14:50 --> 14:52So Mike, Mark was
14:52 --> 14:55talking about how
14:55 --> 14:57we can make nanoparticles sticky.
14:57 --> 15:00We can try to get them in an
15:00 --> 15:03area where these cancers exist.
15:03 --> 15:07What have you explored in terms of
15:07 --> 15:10trying to treat these skin cancers?
15:11 --> 15:13What are the exciting
15:13 --> 15:15developments and where are
15:15 --> 15:17we with this research?
15:17 --> 15:20So I think there's several features that
15:20 --> 15:22we're really leveraging about the sticky
15:22 --> 15:25type particles and these will bind to proteins.
15:25 --> 15:28Any proteins they come in contact
15:28 --> 15:30with but what's really special about the
15:30 --> 15:32tumor microenvironment is that it's
15:32 --> 15:35very protein rich tumor cells secrete
15:35 --> 15:37a lot of proteins.
15:37 --> 15:39They create their own matrix.
15:39 --> 15:41This is helpful for them.
15:41 --> 15:44We think they perceive it as such so they
15:44 --> 15:48can grow so they can begin to want to travel
15:48 --> 15:52if we personify the tumor cells that way,
15:52 --> 15:54and so these particles
15:54 --> 15:57will bind to both tumor matrix proteins and
15:57 --> 16:01bind to the surface of the tumor cells,
16:01 --> 16:03so this really not only gets
16:03 --> 16:06the drugs into the tumor cells,
16:06 --> 16:09but creates anti-tumor
16:09 --> 16:11agents all around the tumor.
16:11 --> 16:14We think this is really important for
16:14 --> 16:17trying to target and eliminate the tumor.
16:17 --> 16:20We also have worked on strategies
16:20 --> 16:22and how we deliver these tiny
16:22 --> 16:25particles beyond the simple
16:25 --> 16:26syringe and needle strategy,
16:26 --> 16:28which is actually quite
16:28 --> 16:30effective in and of itself.
16:30 --> 16:32But for certain tumors,
16:32 --> 16:33for example,
16:33 --> 16:35ones that are more broad
16:35 --> 16:37but thin and shallow,
16:37 --> 16:39they can create surgical challenges
16:39 --> 16:42to cut out a large piece of skin when
16:42 --> 16:45something is really not that deep.
16:45 --> 16:47That lets us wonder if there is a
16:47 --> 16:49way to deliver these agents,
16:49 --> 16:52for example over a larger area,
16:52 --> 16:56but not as deep and so Mark and I have
16:56 --> 16:58explored strategies using what's called
16:58 --> 17:00micro needling or micro needle pads,
17:00 --> 17:02and so the particles might
17:02 --> 17:04be loaded into these hollow
17:04 --> 17:07very tiny needles and in
17:07 --> 17:10many cases they can be made to be
17:10 --> 17:12painless because they just don't
17:12 --> 17:15get to the depth where they're going
17:15 --> 17:17to trigger the nerve endings and
17:17 --> 17:20these pads could be applied and the
17:20 --> 17:22particles can be delivered in that fashion.
17:23 --> 17:25We've also looked at strategies where
17:25 --> 17:27we've accelerated fluid that contains
17:27 --> 17:28the nanoparticles
17:28 --> 17:31in a way that can push them with
17:31 --> 17:34a high pressure system through the
17:34 --> 17:37surface of the skin into a tumor
17:37 --> 17:39and the surrounding area.
17:39 --> 17:43Kind of like a high pressure micro waterjet,
17:43 --> 17:46so we're really looking at ways that
17:46 --> 17:49we can empower health care providers
17:49 --> 17:52to be able to use this technology
17:52 --> 17:54to best serve their patients.
17:54 --> 17:57But in a number of different
17:57 --> 18:00tumor settings, different tumor types,
18:00 --> 18:01different tumor sizes,
18:01 --> 18:03and different tumor depths.
18:03 --> 18:03That's
18:03 --> 18:06really interesting, and I guess the
18:06 --> 18:09other way to do this is,
18:09 --> 18:12as you both were talking about earlier,
18:12 --> 18:14was injecting this systemically.
18:14 --> 18:18So I would think intravenously to try and
18:18 --> 18:20hone these nanoparticles to their target
18:20 --> 18:23whether it's an
18:23 --> 18:26antibody or other mechanism to
18:26 --> 18:29try to find these cancer cells
18:29 --> 18:31and target them that way.
18:31 --> 18:33Mark, you know another concept
18:33 --> 18:34that you had mentioned,
18:34 --> 18:37or I think Mike had mentioned before the
18:37 --> 18:40break was using nanoparticles to kind
18:40 --> 18:43of prime the immune system.
18:43 --> 18:46Often on this show we're talking about
18:46 --> 18:48immunotherapy and the fact that these
18:48 --> 18:51cancers kind of evade the immune system
18:51 --> 18:54whose job it is really to get rid of
18:54 --> 18:57things that we don't want in our body,
18:57 --> 18:59whether it's infections,
18:59 --> 19:01or whether it's tumor cells.
19:01 --> 19:04Tell us a little bit more about
19:04 --> 19:06how you can engineer nanoparticles
19:06 --> 19:09to trigger the immune system,
19:09 --> 19:12and how that's working in treating cancer?
19:13 --> 19:15I'd be happy
19:15 --> 19:16to start addressing that,
19:16 --> 19:19but Mike is really the expert on that part,
19:19 --> 19:21but so I'll talk about the parts that
19:21 --> 19:23I know and maybe he can follow up.
19:26 --> 19:27One of the interesting things about some
19:27 --> 19:30of the cells of the immune system is
19:30 --> 19:32that their naturally bagocytic
19:32 --> 19:35and part of their job is to take up
19:38 --> 19:39particles from the environment
19:39 --> 19:41and to sample them to look for
19:41 --> 19:43danger signals,
19:43 --> 19:44and so you can
19:44 --> 19:46exploit those cells by
19:46 --> 19:48creating nanoparticles that look
19:48 --> 19:50like the natural kinds of things
19:50 --> 19:53that they would take up and ingest.
19:53 --> 19:55And you can do that by controlling
19:55 --> 19:57the size of the particle and by
19:57 --> 19:59controlling its surface to make it
19:59 --> 20:01most attractive to those
20:01 --> 20:04macrophages or antigen presenting cells.
20:04 --> 20:05But in addition,
20:05 --> 20:07you could further
20:07 --> 20:09augment the activity of those
20:09 --> 20:11particles by putting in the kind
20:11 --> 20:14of danger signals that they might
20:14 --> 20:16find from a microorganism and that
20:16 --> 20:19revs up their their immune activity.
20:19 --> 20:21And so we've been exploring that
20:21 --> 20:24and also exploring the idea
20:24 --> 20:27that you could present these
20:27 --> 20:29signals to immune cells
20:29 --> 20:31in a variety of different ways,
20:31 --> 20:33either by slowly releasing them,
20:33 --> 20:35the concept we talked about before,
20:35 --> 20:38or by presenting them in different
20:38 --> 20:40fashions on the surface or the
20:40 --> 20:42interior of the particle and looking
20:42 --> 20:45to see if by changing the way that
20:45 --> 20:47the particle is engineered with these
20:47 --> 20:50signals for the immune system,
20:50 --> 20:51if that changes
20:51 --> 20:54the speed or the aggressiveness
20:54 --> 20:56that you can introduce into
20:56 --> 20:57the immune response.
20:58 --> 21:01So Mike, do you want to
21:01 --> 21:03kind of pick up on that?
21:03 --> 21:05I mean, oftentimes when we're thinking
21:05 --> 21:07about generating an immune response,
21:07 --> 21:10we kind of talked about
21:10 --> 21:11two kinds of systems.
21:13 --> 21:16One that's a more generalized immune response,
21:16 --> 21:17and one that's more targeted.
21:17 --> 21:20Talk a little bit about how you
21:20 --> 21:21envision nanoparticles really
21:21 --> 21:24working in terms of the immune
21:24 --> 21:25response against cancers.
21:26 --> 21:29Yeah, I think it's a critical question.
21:29 --> 21:32I think that cancer therapy today is
21:32 --> 21:35about targeting the tumor and
21:35 --> 21:37it's about manipulating the immune
21:37 --> 21:39system to to maximize the effects
21:40 --> 21:42of the tumor targeting strategies.
21:42 --> 21:45No cancer therapy can ignore today
21:45 --> 21:48what's going on with the immune system.
21:48 --> 21:50It's too powerful an ally in
21:50 --> 21:53the fight against the cancer and
21:53 --> 21:55there's obstacles to overcome,
21:55 --> 21:57so let me explain.
21:57 --> 22:01That first dichotomy is
22:01 --> 22:04that we have evolved to recognize
22:04 --> 22:05foreign substances,
22:05 --> 22:08including antigens on tumor cells
22:08 --> 22:12and we can stimulate the heck out
22:12 --> 22:14of that process through agents,
22:14 --> 22:17as Mark has described, that might
22:17 --> 22:19be considered dangerous signals,
22:19 --> 22:22molecules that might be for example,
22:22 --> 22:25normally found on infectious agents,
22:25 --> 22:28molecules that might be produced by
22:28 --> 22:31our own cells when they have sensed
22:31 --> 22:34that they are infected, for example.
22:34 --> 22:36We can begin to try to trick
22:36 --> 22:38the immune system
22:38 --> 22:40in looking at the cancer cells in
22:40 --> 22:43a way that makes them appear as if
22:43 --> 22:45they're a foreign infection,
22:45 --> 22:47whether that be viral resemblance
22:47 --> 22:49or bacterial resemblance or others.
22:49 --> 22:52And we can do that in a general way,
22:52 --> 22:55and so those are common molecules that
22:55 --> 22:57are found on a bunch of microorganisms,
22:57 --> 23:00so we can just introduce those types
23:00 --> 23:02of compounds into the nanoparticles.
23:02 --> 23:04Then we can try to facilitate
23:04 --> 23:07how they're seen by the immune
23:07 --> 23:09system in a more optimized way.
23:09 --> 23:11In a more specific way,
23:11 --> 23:14we might try to load what
23:14 --> 23:15are called tumor antigens,
23:15 --> 23:18so these might be real signatures
23:18 --> 23:20on very specific types of cancers,
23:20 --> 23:23and they may be even specific
23:23 --> 23:24to each patient.
23:24 --> 23:25In this way,
23:25 --> 23:27we're trying to stimulate a very
23:27 --> 23:30directed killer T cell response.
23:30 --> 23:33That's akin to a vaccine, for example.
23:33 --> 23:36That you know is being discussed
23:36 --> 23:39these days for a bunch of other reasons,
23:39 --> 23:42and so we can use nanoparticles to
23:42 --> 23:45develop anti tumor vaccines that
23:45 --> 23:47could more specifically stimulate
23:47 --> 23:49the immune system
23:53 --> 23:54to attack the cancer.
23:57 --> 23:59And on another consideration though,
23:59 --> 24:02we have to realize that tumors evolve and
24:02 --> 24:05grow to try to suppress the immune system.
24:05 --> 24:07And this is a major major
24:07 --> 24:09consideration in treating cancer,
24:09 --> 24:11immune checkpoint inhibitors or something,
24:11 --> 24:13for example, that are delivered
24:13 --> 24:16throughout the body to try to alleviate
24:16 --> 24:18some of these controls that the
24:18 --> 24:21tumor has put on the immune system.
24:21 --> 24:24But we can also try to target
24:24 --> 24:25that with nanoparticles locally.
24:25 --> 24:28So for example, there are immune cells that
24:28 --> 24:31try to suppress the antitumor effects,
24:31 --> 24:35and these need to be
24:35 --> 24:37dealt with in a way,
24:37 --> 24:39especially at the tumor site,
24:39 --> 24:42so that the tumor can become
24:42 --> 24:45what we call hot and not cold.
24:45 --> 24:48Hot, meaning it can be recognized by the
24:48 --> 24:50antitumor immune system more readily.
24:51 --> 24:54And it sounds like
24:54 --> 24:56you have so many possibilities
24:56 --> 24:59in terms of how you can fashion
24:59 --> 25:01these nanoparticles, so you can
25:01 --> 25:03target the tumor on one
25:04 --> 25:06side and potentially attract the
25:06 --> 25:09immune system on the other side
25:09 --> 25:11and get these two systems in
25:11 --> 25:14close proximity to each other in
25:14 --> 25:16addition to delivering drugs.
25:16 --> 25:19Now the other thing that you mentioned
25:19 --> 25:21before the break was using nanoparticles
25:21 --> 25:24relating to skin cancers,
25:24 --> 25:27but more on the prevention side.
25:27 --> 25:30So Mark talk a little bit about
25:30 --> 25:32using nanoparticles to make
25:32 --> 25:35sunscreens more effective.
25:36 --> 25:39Yeah, I'd be happy to do that and that was one of
25:39 --> 25:42the first big projects that Mike and I
25:42 --> 25:44worked together on and it was quite successful.
25:44 --> 25:48So the idea was that we NOTE Confidence: 0.9900481
25:48 --> 25:50knew that we could make these
25:50 --> 25:52nanoparticles that would adhere to tissues
25:52 --> 25:55and we tested them to see if you just
25:55 --> 25:57suspended these particles,
25:57 --> 26:00these sticky particles and NOTE Confidence: 0.9900481
26:00 --> 26:03you put that water on the skin would
26:03 --> 26:06the particles adhere and in fact they did.
26:06 --> 26:08And they adhered very strongly to the skin.
26:09 --> 26:12You could put some particles on the
26:12 --> 26:14skin and then you could wash the
26:14 --> 26:16skin extensively and the particles
26:16 --> 26:18would just stay there and resist
26:18 --> 26:19removal with washing.
26:19 --> 26:22And so we knew that there was something
26:22 --> 26:23special about that technology,
26:24 --> 26:26because if you can apply something
26:26 --> 26:28topically to the skin and it
26:28 --> 26:30stays there for a long time,
26:30 --> 26:31that might have some value.
26:31 --> 26:34And so in the second phase we learned that
26:34 --> 26:37one could take common sunscreen ingredients
26:37 --> 26:40and load them at very high levels
26:40 --> 26:41inside these nanoparticles,
26:41 --> 26:43so that the nanoparticle itself
26:43 --> 26:45was 50 percent, 60%,
26:45 --> 26:47sometimes even 70% sunscreen agent.
26:47 --> 26:50And then if you apply those to the
26:50 --> 26:52surface of the skin, they stuck.
26:52 --> 26:54They don't penetrate into the skin.
26:54 --> 26:57They don't wash off very easily,
26:57 --> 27:00but they're sitting on the skin now in
27:00 --> 27:03a position to be between the skin and
27:03 --> 27:06any ultraviolet light that falls on the skin,
27:06 --> 27:08and so they could be
27:08 --> 27:11very effective at screening that
27:11 --> 27:13ultraviolet light and and absorbing
27:13 --> 27:16it and blocking it without anything
27:16 --> 27:19ever entering your body and they
27:19 --> 27:21stay on there for a long time.
27:21 --> 27:24And so we did a number of studies
27:24 --> 27:27trying to understand how this works and
27:27 --> 27:30trying to perfect it using combinations
27:30 --> 27:34of sunscreens so that we could block
27:34 --> 27:35all wavelengths of ultraviolet
27:35 --> 27:38light and ultimately did a
27:38 --> 27:41small pilot clinical trial
27:41 --> 27:43here at Yale showing that
27:43 --> 27:46indeed you could put these on the
27:46 --> 27:48surface of the skin of volunteers
27:48 --> 27:51that they were completely safe and
27:51 --> 27:54Mike can talk about the details of
27:54 --> 27:57that and that they would perform just
27:57 --> 27:59as well as the kinds of sunscreens
27:59 --> 28:02that you can buy at the drugstore.
28:02 --> 28:04So we're very excited about that
28:05 --> 28:08and new ways
28:08 --> 28:09to use technology
28:09 --> 28:11to prevent skin cancer.
28:16 --> 28:19And my grandparents all worked on
28:19 --> 28:21farms and so are very familiar with the
28:21 --> 28:24devastating effects
28:24 --> 28:26of skin cancer.
28:26 --> 28:28Doctor W. Mark Saltzman is a professor
28:28 --> 28:29of biomedical engineering,
28:29 --> 28:31cellular and molecular Physiology
28:31 --> 28:32and of chemical engineering
28:32 --> 28:34and Doctor Michael Girardi is
28:34 --> 28:36a professor of dermatology at
28:36 --> 28:38the Yale School of Medicine.
28:38 --> 28:41If you have questions the address
28:41 --> 28:41is canceranswers@yale.edu.
28:41 --> 28:43And past editions of the program
28:43 --> 28:45are available in audio and written
28:45 --> 28:47form at yalecancercenter.org.
28:47 --> 28:49We hope you'll join us next week to
28:49 --> 28:51learn more about the fight against
28:51 --> 28:53cancer here on Connecticut Public
28:53 --> 28:55radio funding for Yale Cancer
28:55 --> 28:57Answers is provided by Smilow
28:57 --> 29:00Cancer Hospital and AstraZeneca.

Information

Using Nanoparticles to treat Skin Cancer with guests Dr. W. Mark Saltzman and Dr. Michael Girardi August 8, 2021 Yale Cancer Center visit: http://www.yalecancercenter.org email: canceranswers@yale.edu call: 203-785-4095