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Angew Chem Int Ed Engl ; 62(16): e202218218, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36811315

ABSTRACT

Nanoparticles' uptake by cancer cells upon reaching the tumor microenvironment is often the rate-limiting step in cancer nanomedicine. Herein, we report that the inclusion of aminopolycarboxylic acid conjugated lipids, such as EDTA- or DTPA-hexadecylamide lipids in liposome-like porphyrin nanoparticles (PS) enhanced their intracellular uptake by 25-fold, which was attributed to these lipids' ability to fluidize the cell membrane in a detergent-like manner rather than by metal chelation of EDTA or DTPA. EDTA-lipid-incorporated-PS (ePS) take advantage of its unique active uptake mechanism to achieve >95 % photodynamic therapy (PDT) cell killing compared to <5 % cell killing by PS. In multiple tumor models, ePS demonstrated fast fluorescence-enabled tumor delineation within minutes post-injection and increased PDT potency (100 % survival rate) compared to PS (60 %). This study offers a new nanoparticle cellular uptake strategy to overcome challenges associated with conventional drug delivery.


Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Liposomes , Edetic Acid , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Lipids , Pentetic Acid , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Cell Line, Tumor , Tumor Microenvironment
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