Nanoparticles Containing a Combination of a Drug and an Antibody for the Treatment of Breast Cancer Brain Metastases.

Abstract:

: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.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Wyatt EA,Davis ME

doi

10.1021/acs.molpharmaceut.9b01167

subject

Has Abstract

pub_date

2020-02-03 00:00:00

pages

717-721

issue

2

eissn

1543-8384

issn

1543-8392

journal_volume

17

pub_type

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