A Library of Custom PEG-Lipids reveals a Double-PEG-Lipid with Drastically Enhanced Paclitaxel Solubility and Human Cancer Cell Cytotoxicity when used in Fluid Micellar Nanoparticles.

Paclitaxel (PTX) is one of the most widely utilized chemotherapeutics globally. However, the extremely poor water solubility of paclitaxel necessitates a mechanism of delivery within blood. Fluid lipid PTX nanocarriers (lipids in the chain-melted state) show promise as PTX delivery vectors, but remain limited by their solubility of PTX within the membrane.

Cancerous pH-responsive polycarboxybetaine-coated lipid nanoparticle for smart delivery of siRNA against subcutaneous tumor model in mice.

Lipid nanoparticles (LNPs) have been commonly used as a vehicle for nucleic acids, such as small interfering RNA (siRNA); the surface modification of LNPs is one of the determinants of their delivery efficiency especially in systemic administration. However, the applications of siRNA-encapsulated LNPs are limited due to a lack effective systems to deliver to solid tumors. Here, we report a smart surface modification using a charge-switchable ethylenediamine-based polycarboxybetaine for enhancing tumor accumulation via interaction with anionic tumorous tissue constituents due to selective switching to cationic charge in response to cancerous acidic pH.