{"id":1586,"date":"2025-07-22T16:42:18","date_gmt":"2025-07-22T20:42:18","guid":{"rendered":"https:\/\/blog.richmond.edu\/pollocklab\/?p=1586"},"modified":"2025-07-22T16:42:18","modified_gmt":"2025-07-22T20:42:18","slug":"metal-based-chemotherapy-a-new-form-of-cancer-treatment","status":"publish","type":"post","link":"https:\/\/create.richmond.edu\/pollocklab\/2025\/07\/22\/metal-based-chemotherapy-a-new-form-of-cancer-treatment\/","title":{"rendered":"Metal-Based Chemotherapy: A New Form of Cancer Treatment"},"content":{"rendered":"<p>[et_pb_section bb_built=&#8221;1&#8243;][et_pb_row][et_pb_column type=&#8221;4_4&#8243;][et_pb_text _builder_version=&#8221;4.27.4&#8243; background_pattern_color=&#8221;rgba(0,0,0,0.2)&#8221; background_mask_color=&#8221;#ffffff&#8221; vertical_offset_tablet=&#8221;0&#8243; horizontal_offset_tablet=&#8221;0&#8243; z_index_tablet=&#8221;0&#8243; text_text_shadow_horizontal_length=&#8221;text_text_shadow_style,%91object Object%93&#8243; text_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; 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header_3_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_3_text_shadow_vertical_length=&#8221;header_3_text_shadow_style,%91object Object%93&#8243; header_3_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_3_text_shadow_blur_strength=&#8221;header_3_text_shadow_style,%91object Object%93&#8243; header_3_text_shadow_blur_strength_tablet=&#8221;1px&#8221; header_4_text_shadow_horizontal_length=&#8221;header_4_text_shadow_style,%91object Object%93&#8243; header_4_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_4_text_shadow_vertical_length=&#8221;header_4_text_shadow_style,%91object Object%93&#8243; header_4_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_4_text_shadow_blur_strength=&#8221;header_4_text_shadow_style,%91object Object%93&#8243; header_4_text_shadow_blur_strength_tablet=&#8221;1px&#8221; header_5_text_shadow_horizontal_length=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_5_text_shadow_vertical_length=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_5_text_shadow_blur_strength=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_blur_strength_tablet=&#8221;1px&#8221; header_6_text_shadow_horizontal_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_6_text_shadow_vertical_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_6_text_shadow_blur_strength=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_blur_strength_tablet=&#8221;1px&#8221; box_shadow_horizontal_tablet=&#8221;0px&#8221; box_shadow_vertical_tablet=&#8221;0px&#8221; box_shadow_blur_tablet=&#8221;40px&#8221; box_shadow_spread_tablet=&#8221;0px&#8221; text_orientation=&#8221;justified&#8221;]<\/p>\n<p><span style=\"font-weight: 400\">Cancer is the leading cause of death worldwide. Thanks to advances in medicine, deaths from communicable diseases have decreased, and life expectancy has increased. However, with people living longer, there is a greater chance of developing noncommunicable diseases like cancer in their lifetime. So, despite medical progress, why are people still dying from cancer?<\/span><\/p>\n<p><span style=\"font-weight: 400\">Cancer is the uncontrolled growth of abnormal cells, and there are hundreds of types, each requiring different treatment approaches. Its ability to mutate quickly makes it especially difficult to treat. Standard cancer treatments include surgery, radiation therapy, immunotherapy, hormone therapy, and one of the most widely used chemotherapy.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Chemotherapy uses drugs to kill or slow the growth of cancer cells. While effective, it also harms healthy cells, leading to a range of side effects. This has driven search for <\/span><span style=\"font-weight: 400\">developing new and improved treatments<\/span><span style=\"font-weight: 400\">. One promising area of research is metal-based chemotherapy.<\/span><\/p>\n<p><b>The Discovery of Cisplatin<\/b><\/p>\n<p><span style=\"font-weight: 400\">Cisplatin was the first metal-based anticancer drug, discovered in the 1960s and approved by the FDA in 1978. <\/span><span style=\"font-weight: 400\">This compound is a platinum (Pt) based drug bound to two chloride (Cl)\u00a0 ions and two ammonia (NH3) groups in a square planar geometry. <\/span><span style=\"font-weight: 400\">\u00a0<\/span><span style=\"font-weight: 400\">The arrangement of the groups bound to platinum is extremely important as the cis isomer, <\/span><span style=\"font-weight: 400\">where the chlorides are next to each other<\/span><span style=\"font-weight: 400\">, exhibits anticancer properties while the trans isomer, <\/span><span style=\"font-weight: 400\">where the chlorides are across from each other<\/span><span style=\"font-weight: 400\">, does not.\u00a0<\/span><\/p>\n<p>[\/et_pb_text][et_pb_image _builder_version=&#8221;4.27.4&#8243; 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header_5_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_5_text_shadow_blur_strength=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_blur_strength_tablet=&#8221;1px&#8221; header_6_text_shadow_horizontal_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_6_text_shadow_vertical_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_6_text_shadow_blur_strength=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_blur_strength_tablet=&#8221;1px&#8221; box_shadow_horizontal_tablet=&#8221;0px&#8221; box_shadow_vertical_tablet=&#8221;0px&#8221; box_shadow_blur_tablet=&#8221;40px&#8221; box_shadow_spread_tablet=&#8221;0px&#8221;]<\/p>\n<p><span style=\"font-weight: 400\">Once inside the body, cisplatin becomes activated when the chloride ions are replaced by water molecules. The activated drug binds to DNA, damaging it and triggering cell death.\u00a0 It has also been found that cisplatin could produce reactive oxygen species (ROS), which also leads to cell death. While extremely effective at killing cancer cells, cisplatin has several side effects, including many toxicities, and emerging resistance. This has led to the development of other platinum-based drugs like carboplatin, known for having fewer side effects. The success of cisplatin opened the door to exploring other transition metals for cancer treatment.<\/span><\/p>\n<p><b>Why Transition Metals?<\/b><\/p>\n<p>[\/et_pb_text][et_pb_image _builder_version=&#8221;4.27.4&#8243; src=&#8221;https:\/\/create.richmond.edu\/wp\/wp-content\/uploads\/sites\/25\/2025\/07\/PeriodicTableBW2017.png&#8221; background_pattern_color=&#8221;rgba(0,0,0,0.2)&#8221; background_mask_color=&#8221;#ffffff&#8221; align=&#8221;center&#8221; box_shadow_horizontal_tablet=&#8221;0px&#8221; box_shadow_vertical_tablet=&#8221;0px&#8221; box_shadow_blur_tablet=&#8221;40px&#8221; box_shadow_spread_tablet=&#8221;0px&#8221; vertical_offset_tablet=&#8221;0&#8243; horizontal_offset_tablet=&#8221;0&#8243; z_index_tablet=&#8221;0&#8243; \/][et_pb_text _builder_version=&#8221;4.27.4&#8243; background_pattern_color=&#8221;rgba(0,0,0,0.2)&#8221; background_mask_color=&#8221;#ffffff&#8221; vertical_offset_tablet=&#8221;0&#8243; horizontal_offset_tablet=&#8221;0&#8243; z_index_tablet=&#8221;0&#8243; 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header_5_text_shadow_horizontal_length=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_5_text_shadow_vertical_length=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_5_text_shadow_blur_strength=&#8221;header_5_text_shadow_style,%91object Object%93&#8243; header_5_text_shadow_blur_strength_tablet=&#8221;1px&#8221; header_6_text_shadow_horizontal_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_horizontal_length_tablet=&#8221;0px&#8221; header_6_text_shadow_vertical_length=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_vertical_length_tablet=&#8221;0px&#8221; header_6_text_shadow_blur_strength=&#8221;header_6_text_shadow_style,%91object Object%93&#8243; header_6_text_shadow_blur_strength_tablet=&#8221;1px&#8221; box_shadow_horizontal_tablet=&#8221;0px&#8221; box_shadow_vertical_tablet=&#8221;0px&#8221; box_shadow_blur_tablet=&#8221;40px&#8221; box_shadow_spread_tablet=&#8221;0px&#8221;]<\/p>\n<p><span style=\"font-weight: 400\">Transition metals have unique properties that make them ideal for drug development. They can exist in multiple oxidation states, giving them reduction-oxidation (redox) potential. They also bind to a variety of ligands, molecules that attach to the metal, making it possible to design a wide range of compounds with different pharmacological properties. As seen with cisplatin, even changes such as reducing the metal and substituting or releasing ligands can significantly impact how the drug behaves and interacts with cells.<\/span><\/p>\n<p><b>Light-Activated Prodrugs<\/b><\/p>\n<p><span style=\"font-weight: 400\">Developing drugs with improved efficiency and safety requires increased selectivity to cancerous cells and reduced toxicity to healthy cells. An effective approach is developing prodrug treatments, such as photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), which both utilize light-activated prodrugs. Prodrugs are compounds that have little to no pharmacological activity, in this case toxicity, until they have become activated. By delivering light at a specific wavelength to the targeted area only the compound in the spot treated with light will become toxic, so there is minimal damage to healthy cells.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">PDT prodrugs transfers electrons or energy to dioxygen (O2) when exposed to light producing ROS which creates oxidative stress and eventually cell death. PDT works best in well oxygenated tissue in order to develop more ROS to kill more cancer cells. PACT prodrugs work by a different mechanism. <\/span><span style=\"font-weight: 400\">When activated the PACT prodrug will release a ligand so that the metal component or newly released ligand are now toxic and kill the cancer cells.\u00a0<\/span><\/p>\n<p><b>Ruthenium Compounds<\/b><\/p>\n<p><span style=\"font-weight: 400\">One of the more studied metals for chemotherapy drugs is ruthenium (Ru). Ru(III) is less toxic and more selective than platinum. It can mimic iron (Fe), allowing it to bind to transferrin, the protein that transports iron into cells. Since cancer cells have a higher demand for iron, this mechanism helps ruthenium compounds more easily enter tumor cells. <\/span><span style=\"font-weight: 400\">Under physiological conditions ruthenium has two stable oxidation states Ru(III) and Ru(II), which is more reactive.<\/span> <span style=\"font-weight: 400\">Once reduced, Ru(II)<\/span><span style=\"font-weight: 400\"> can bind to DNA or proteins, ultimately killing the cell. This reduction can even be triggered by light, making ruthenium an ideal candidate for PACT.<\/span><\/p>\n<p><b>Cobalt Compound<\/b><\/p>\n<p><span style=\"font-weight: 400\">Another less studied potential metal for chemotherapy drugs is cobalt (Co). Similar to ruthenium, cobalt has two stable oxidation states under physiological conditions. Co(III) can be reduced to Co(II), a more toxic form. While its exact mechanism of action is still under investigation, cobalt holds potential as a metal-based chemotherapy.<\/span><\/p>\n<p><b>The Future<\/b><\/p>\n<p><span style=\"font-weight: 400\">In our lab, I am testing ruthenium- and cobalt-based prodrugs as potential chemotherapy agents. These compounds aim to be more selective and less toxic, making them a more effective and safer way to treat cancer. The continued development of metal-based chemotherapy drugs could be revolutionary for cancer treatment.<\/span><\/p>\n<p><b>Vienna Tombline<\/b><\/p>\n<p><b>Class of 2027<\/b><\/p>\n<p><b>Chemistry Major<\/b><\/p>\n<p>\u00a0<\/p>\n<p><span style=\"font-weight: 400\">Adhikari, S.; Nath, P.; Das, A.; Datta, A.; Baildya, N.; Duttaroy, A. K.; Pathak, S.; A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies. <\/span><i><span style=\"font-weight: 400\">Biomedicine &amp; Pharmacotherapy<\/span><\/i> <b>2024<\/b><span style=\"font-weight: 400\">, 171, 116211.<\/span> <a href=\"https:\/\/doi.org\/10.1016\/j.biopha.2024.116211\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1016\/j.biopha.2024.116211<\/span><\/a><span style=\"font-weight: 400\">.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Casini, A.; P\u00f6thig, A.; Metals in Cancer Research: Beyond Platinum Metallodrugs. <\/span><i><span style=\"font-weight: 400\">ACS Central Science<\/span><\/i> <b>2024,<\/b> <i><span style=\"font-weight: 400\">10<\/span><\/i><span style=\"font-weight: 400\"> (2), 242-250.<\/span> <a href=\"https:\/\/doi.org\/10.1021\/acscentsci.3c01340\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1021\/acscentsci.3c01340<\/span><\/a><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Graf, N.; Lippard, S. J.; Redox activation of metal-based prodrugs as a strategy for drug delivery. <\/span><i><span style=\"font-weight: 400\">Advanced Drug Delivery Reviews<\/span><\/i><span style=\"font-weight: 400\">. <\/span><b>2012<\/b><span style=\"font-weight: 400\">, 64 (11), 993-1004. <\/span><a href=\"https:\/\/doi.org\/10.1016\/j.addr.2012.01.007\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1016\/j.addr.2012.01.007<\/span><\/a><span style=\"font-weight: 400\">.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Lee, S. Y.; Kim, C. Y.; Nam, T.; Ruthenium Complexes as Anticancer Agents: A Brief History and Perspectives. <\/span><i><span style=\"font-weight: 400\">Drug Design, Development and Therapy<\/span><\/i><span style=\"font-weight: 400\">. <\/span><b>2020<\/b><span style=\"font-weight: 400\">, <\/span><i><span style=\"font-weight: 400\">14<\/span><\/i><span style=\"font-weight: 400\">, 5375\u20135392. <\/span><a href=\"https:\/\/doi.org\/10.2147\/DDDT.S275007\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.2147\/DDDT.S275007<\/span><\/a><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Lucaciu, R.L.; Hangan, A.C.; Sevastre, B.; Oprean, L.S. Metallo-Drugs in Cancer Therapy: Past, Present and Future. <\/span><i><span style=\"font-weight: 400\">Molecules<\/span><\/i> <b>2022<\/b><span style=\"font-weight: 400\">, <\/span><i><span style=\"font-weight: 400\">27<\/span><\/i><span style=\"font-weight: 400\">, 6485.<\/span> <a href=\"https:\/\/doi.org\/10.3390\/molecules27196485\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.3390\/molecules27196485<\/span><\/a><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Ndagi, U.; Mhlongo, N.; Soliman, ME.; Metal complexes in cancer therapy \u2013 an update from drug design perspective. <\/span><i><span style=\"font-weight: 400\">Drug Des Devel Ther<\/span><\/i><span style=\"font-weight: 400\">. <\/span><b>2017<\/b><span style=\"font-weight: 400\">, 11, 599-616. <\/span><a href=\"https:\/\/doi.org\/10.2147\/DDDT.S119488\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.2147\/DDDT.S119488<\/span><\/a><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">Unavane, S.; Patil, R.; Syed, S.; Jain, H. K.; Exploring the therapeutic potential of copper and cobalt complexes as anticancer agents: a comprehensive review. <\/span><i><span style=\"font-weight: 400\">Transit Met Chem<\/span><\/i> <b>2025<\/b><span style=\"font-weight: 400\">. <\/span><a href=\"https:\/\/doi.org\/10.1007\/s11243-024-00630-6\"><span style=\"font-weight: 400\">https:\/\/doi.org\/10.1007\/s11243-024-00630-6<\/span><\/a><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"<p><div class=\"et_pb_row et_pb_row_0 et_pb_row_empty\">\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div> Cancer is the leading cause of death worldwide. Thanks to advances in medicine, deaths from communicable diseases have decreased, and life expectancy has increased. However, with people living longer, there is a greater chance of developing noncommunicable diseases like cancer in their lifetime. So, despite medical progress, why are people still dying from cancer?Cancer [&hellip;]<\/p>\n","protected":false},"author":6701,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[795,508,35898],"tags":[],"class_list":["post-1586","post","type-post","status-publish","format-standard","hentry","category-blog","category-research","category-students"],"_links":{"self":[{"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/posts\/1586","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/users\/6701"}],"replies":[{"embeddable":true,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/comments?post=1586"}],"version-history":[{"count":3,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/posts\/1586\/revisions"}],"predecessor-version":[{"id":1591,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/posts\/1586\/revisions\/1591"}],"wp:attachment":[{"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/media?parent=1586"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/categories?post=1586"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/create.richmond.edu\/pollocklab\/wp-json\/wp\/v2\/tags?post=1586"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}