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Ultrasound Imaging-Guided Miniature Robots Enable Targeted Drug Delivery Directly to Tumor Site

By MedImaging International staff writers
Posted on 12 Dec 2024
Image: Scanning electron microscope image of the printed bioresorbable acoustic hydrogel microrobots (Photo courtesy of Hong Han/Caltech)
Image: Scanning electron microscope image of the printed bioresorbable acoustic hydrogel microrobots (Photo courtesy of Hong Han/Caltech)

In the future, miniature robots may be tasked with delivering therapeutic drugs directly to targeted areas within the body. Instead of the traditional metal humanoid robots, they would be in the form of tiny, bubble-like spheres. Such robots would need to meet several stringent requirements, including surviving in bodily fluids like stomach acid, being controllable to direct them precisely to the target area, releasing their medicinal contents only upon reaching the target, and being absorbable without causing harm. Now, researchers have developed bioresorbable acoustic microrobots (BAM) that meet all of these criteria and have been shown to deliver therapeutics to reduce bladder tumor sizes in mice.

Micro- and nanorobots have been in development for two decades, but their practical application in living systems has been limited. The challenge has been the difficulty of moving objects with precision in complex biological fluids such as blood, urine, or saliva. Additionally, these robots must be biocompatible and bioresorbable, meaning they must not leave behind any toxic materials. The new microrobots, developed by researchers from the California Institute of Technology (Pasadena, CA, USA), are spherical microstructures made from a hydrogel called poly(ethylene glycol) diacrylate. Hydrogels are materials that start in a liquid or resin form but solidify once the polymers inside them cross-link, making them ideal for retaining fluids and being biocompatible. The manufacturing method for these microrobots allows the outer spheres to carry therapeutic drugs to target sites in the body.

To create these microrobots, the team utilized two-photon polymerization (TPP) lithography, a precise technique that uses infrared laser pulses to cross-link photosensitive polymers into a specific pattern. This allows the microrobots to be constructed with remarkable precision, layer by layer, similar to a 3D printing process but with much finer detail. The resulting microrobots are about 30 microns in diameter, roughly the size of a human hair, and contain magnetic nanoparticles along with the therapeutic drug within their spherical structure. These magnetic nanoparticles enable the microrobots to be directed by an external magnetic field, allowing them to reach their desired location. Upon arrival, the robots remain in place while the drug is passively released, as described in the journal Science Robotics.

The exterior of the microrobot is hydrophilic (water-attracting), ensuring that the robots do not clump together as they move through the body. However, the interior must be hydrophobic (water-repelling) to trap an air bubble, essential for movement. To achieve this, the team developed a two-step chemical modification. First, they attached long-chain carbon molecules to the hydrogel, making the entire structure hydrophobic. Then, they used oxygen plasma etching to remove the carbon chains from the interior, leaving it hydrophilic while maintaining the hydrophobic exterior. This modification enabled the robots to trap bubbles for longer durations, ranging from several days instead of the few minutes they would typically last. The bubbles are crucial for both movement and real-time imaging. The robots have two cylindrical openings—one at the top and another on the side. The research team found that the use of two openings gave the robots the ability to move not only in various viscous biofluids, but also at greater speeds than can be achieved with a single opening.

The team developed a way to track the microrobots as they move to their targets with the help of ultrasound imaging. Trapped within each microstructure is an egg-like bubble that serves as an excellent ultrasound imaging contrast agent, enabling real-time monitoring of the bots in vivo. When exposed to an ultrasound field, the bubbles vibrate, creating a flow of fluid that propels the robots. The team tested the microrobots as a drug-delivery tool in mice with bladder tumors. The results showed that administering therapeutics using the microrobots was more effective at shrinking tumors compared to traditional drug delivery methods. Over 21 days, four doses of therapeutic drugs delivered by the microrobots resulted in greater tumor reduction, demonstrating the potential of this technology for future therapeutic applications.

"We think this is a very promising platform for drug delivery and precision surgery," said Wei Gao, professor of medical engineering at Caltech. "Looking to the future, we could evaluate using this robot as a platform to deliver different types of therapeutic payloads or agents for different conditions. And in the long term, we hope to test this in humans."

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88 (46.014785766602): SELECT show_live FROM jos_com_show_setting LIMIT 1
89 (617.98095703125): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294803408 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
90 (53.167343139648): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`
91 (83.92333984375): SELECT show_live FROM jos_com_show_setting LIMIT 1
92 (55.074691772461): SELECT show_live FROM jos_com_show_setting LIMIT 1
93 (277.04238891602): SELECT show_live FROM jos_com_show_setting LIMIT 1
94 (267.02880859375): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (!!!!! 3685.9512329102): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (68.902969360352): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (51.021575927734): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (32.186508178711): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (34.093856811523): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1
105 (784.87396240234): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
106 (!!!!! 3851.1753082275): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
107 (!!!!! 1584.0530395508): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294803408 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 1050.9490966797): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
109 (!!!!! 5302.1907806396): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
110 (460.86311340332): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294803408 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (344.99168395996): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294803406 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (586.98654174805): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294803406 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
113 (847.10121154785): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
114 (703.81164550781): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1
115 (!!!!! 5463.1233215332): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
116 (106.8115234375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
117 (77.962875366211): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
118 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
119 (69.856643676758): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
120 (57.93571472168): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
121 (95.844268798828): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
122 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
123 (!!!!! 3590.1069641113): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
124 (!!!!! 56174.039840698): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7
125 (675.91667175293): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294803408 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294803408 AND type='deeppockets_item' AND published='1' LIMIT 1
126 (!!!!! 26890.993118286): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
127 (79.154968261719): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3
128 (438.92860412598): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
129 (59.127807617188): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1
130 (317.09671020508): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
131 (41.007995605469): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1
132 (40.054321289062): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
133 (44.107437133789): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1
134 (344.03800964355): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
135 (46.014785766602): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1
136 (306.12945556641): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (245.09429931641): SELECT name FROM jos_deeppockets WHERE id=214
138 (44.822692871094): SELECT name FROM jos_deeppockets WHERE id=214
139 (!!!!! 3359.7946166992): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))214((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (931.0245513916): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))214((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (119.92454528809): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
142 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
143 (!!!!! 28376.10244751): TRUNCATE TABLE jos_trademed_module
144 (787.01972961426): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294803408 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (735.99815368652): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
146 (102.04315185547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (113.96408081055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
148 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
149 (!!!!! 1713.0374908447): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6
150 (87.976455688477): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
151 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
152 (61.03515625): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294803408 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294803408 AND type='deeppockets_item' AND published='1' LIMIT 1
153 (44.822692871094): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=0 or channel_id is null)
154 (41.007995605469): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=0 or channel_id is null)
155 (61.988830566406): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
156 (174.99923706055): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
157 (775.81405639648): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294803408 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294803408 AND published='1' LIMIT 1
158 (99.897384643555): select jos_twitters.link from jos_twitters where cat=10
159 (43.869018554688): select jos_facebook.link from jos_facebook where cat=10
160 (42.915344238281): select jos_google_plus.link from jos_google_plus where cat=10
161 (39.100646972656): select jos_linkedin.link from jos_linkedin where cat=10
162 (372.17140197754): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14202,14203)
163 (!!!!! 1216.1731719971): insert into jos_banners_delta values (14202,'2025-08-01 22:21:58','216.73.216.210','view'),(14203,'2025-08-01 22:21:58','216.73.216.210','view')