Mechanistic insights from simulations of drug-drug conjugate nanoclusters for co-delivery across cancer cell membranes.

ABSTRACT: Amphiphilic drug-drug conjugates (ADDCs) such as gemcitabine-camptothecin (GEM-CPT) and doxorubicin-10-hydroxycamptothecin (DOX-HCPT) nanoclusters offer innovative solutions to overcome the limitations of conventional cancer therapies, including poor solubility and nonspecific targeting. Using molecular dynamics (MD) simulations, we explored the mechanisms by which these nanoclusters interact with and penetrate cancer and normal cell membranes. GEM-CPT exhibited enhanced membrane penetration in cancer cells through combined hydrophilic and hydrophobic interactions, along with its ability to extract cholesterol and induce membrane remodelling. In contrast, DOX-HCPT maintained structural integrity through stable π-π stacking interactions, showing selective binding to membrane head groups (HG

SUBMITTER: Choodet C 

PROVIDER: S-EPMC11983680 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature