Novel Strategy to Drive the Intracellular Uptake of Lipid Nanoparticles for Photodynamic Therapy

Abstract

Nanoparticles' uptake by cancer cells upon reaching the tumor microenvironment is often the ratelimiting 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-lipidincorporated-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.

Structural Effect of Rhenium‐ and Iridium‐Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy

“…In summary, four main formulations of liposome were synthesized for each metal complex. The first formulation design was based on a successful formulation of porphyrin‐based liposome for cancer PDT, [ 22 ] which consists of 40% cholesterol and 5% 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐ N ‐[methoxy(polyethylene glycol)‐2000] (PEG‐lipid). Building upon this formulation, we designed and synthesized Re‐HC and Ir‐HC liposomes (HC indicating high cholesterol content) containing 40% cholesterol, 5% PEG‐lipid, 25% Re‐lipid or Ir‐lipid, and 30% distearoylphosphatidylcholine (DSPC) as the base lipid.…”

“…This design was based on our recent discovery of incorporating EDTA‐lipid into liposomal nanoparticles, enabling the fluidization of the cell membrane in a detergent‐like manner to promote intramembrane uptake of nanoparticles. [ 22 ] The third formulation had a lower content of cholesterol (17%) and PEG‐lipid (2%), with dipalmitoylphosphatidylcholine (DPPC) as the base lipid instead of DSPC. These formulations were named Re‐LC and Ir‐LC, where LC indicates the low cholesterol content.…”

Biomedical Application of Porphyrin-Based Amphiphiles and Their Self-Assembled Nanomaterials

“…Enhancing the cellular uptake efficiency of PBAs is critical to improve their therapeutic effect. , Recently, Ho et al reported an EDTA-lipid incorporated-porphysome (ePS) which was formed by a mixture of porphyrin-based lipids and EDTA-lipids . The ePS could achieve >95% PDT cell killing efficiency, which was 19 times higher than EDTA-lipids-free porphysome.…”

“…82,210 Recently, Ho et al reported an EDTA-lipid incorporated-porphysome (ePS) which was formed by a mixture of porphyrin-based lipids and EDTA-lipids. 211 The ePS could achieve >95% PDT cell killing efficiency, which was 19 times higher than EDTA-lipidsfree porphysome. The result demonstrated that EDTA could improve the cell uptake efficiency in certain circumstances.…”

Acyclic cucurbit[n]uril-based nanosponges significantly enhance the photodynamic therapeutic efficacy of temoporfin in vitro and in vivo

“…[16][17][18] Nanoscale DDSs may help accumulate PSs in tumor by the enhanced permeability and retention (EPR) effect. Different types of DDSs have been developed for the delivery of PDT PSs, including inorganic nanoparticles, [19][20][21] cross-linked polymeric nanoparticles, 22,23 vesicles [24][25][26][27] and organic framework materials. 28,29 The key criteria for the design of PDT DDSs include facile preparation, stable encapsulation during circulation, good biocompatibility and improved efficacy.…”