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Triggered Release Enhances the Cytotoxicity of Stable Colloidal Drug Aggregates.

ABSTRACT: Chemotherapeutics that self-assemble into colloids have limited efficacy above their critical aggregation concentration due to their inability to penetrate intact plasma membranes. Even when colloid uptake is promoted, issues with colloid escape from the endolysosomal pathway persist. By stabilizing acid-responsive lapatinib colloids through coaggregation with fulvestrant, and inclusion of transferrin, we demonstrate colloid internalization by cancer cells, where subsequent lapatinib ionization leads to endosomal leakage and increased cytotoxicity. These results demonstrate a strategy for triggered drug release from stable colloidal aggregates.

SUBMITTER: Donders EN

PROVIDER: S-EPMC7136197 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Triggered Release Enhances the Cytotoxicity of Stable Colloidal Drug Aggregates.

Donders Eric N EN Ganesh Ahil N AN Torosyan Hayarpi H Lak Parnian P Shoichet Brian K BK Shoichet Molly S MS

ACS chemical biology 20190625 7

Chemotherapeutics that self-assemble into colloids have limited efficacy above their critical aggregation concentration due to their inability to penetrate intact plasma membranes. Even when colloid uptake is promoted, issues with colloid escape from the endolysosomal pathway persist. By stabilizing acid-responsive lapatinib colloids through coaggregation with fulvestrant, and inclusion of transferrin, we demonstrate colloid internalization by cancer cells, where subsequent lapatinib ionization ...[more]

PMID: 31243955

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