Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases.
In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to permeate the blood-brain and blood-tumor barriers (BBB and BTB) in therapeutic amounts. Here, we investigate the potential of mucic acid-based, targeted nanoparticles designed to transcytose the BBB/BTB to deliver a small molecule drug, camptothecin (CPT), and therapeutic antibody, Herceptin, to brain metastases in mice. Treatment with BBB-targeted combination CPT/Herceptin nanoparticles significantly inhibits tumor growth compared to free CPT/Herceptin and BBB-targeted nanoparticles carrying CPT alone. Though not as efficacious, BBB-targeted nanoparticles carrying only Herceptin also elicit considerable antitumor activity. These results demonstrate the potential of the targeted nanoparticle system for the delivery of an antibody alone or in combination with other drugs across the BBB/BTB to improve the therapeutic outcome.
['Wyatt|Emily A|EA|https://orcid.org/0000-0002-7534-0582', 'Davis|Mark E|ME|0000-0001-8294-1477']
D000818:Animals D000074322:Antineoplastic Agents, Immunological D000972:Antineoplastic Agents, Phytogenic D001812:Blood-Brain Barrier D001932:Brain Neoplasms D001943:Breast Neoplasms D002166:Camptothecin D045744:Cell Line, Tumor D004338:Drug Combinations D016503:Drug Delivery Systems D005260:Female D006801:Humans D051379:Mice D053758:Nanoparticles D013400:Sugar Acids D000068878:Trastuzumab D016896:Treatment Outcome D047368:Tumor Burden D023041:Xenograft Model Antitumor Assays
camptothecin Herceptin blood−brain barrier polymeric nanoparticle systemic delivery