A Dual‐Responsive Mesoporous Silica Nanoparticle for Tumor‐Triggered Targeting Drug Delivery

A novel pH‐ and redox‐ dual‐responsive tumor‐triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox‐responsive, as a gatekeeper as well as a tumor‐targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic‐imine bond, which is pH‐sensitive, are then connected via “click” chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic‐imine bond under acidic conditions. After deshielding of the MPEG segment, the drug‐loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.     

Rapid Light‐Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin–Phospholipids

Prompt membrane permeabilization is a requisite for liposomes designed for local stimuli‐induced intravascular release of therapeutic payloads. Incorporation of a small amount (i.e., 5 molar percent) of an unsaturated phospholipid, such as dioleoylphosphatidylcholine (DOPC), accelerates near infrared (NIR) light‐triggered doxorubicin release in porphyrin–phospholipid (PoP) liposomes by an order of magnitude. In physiological conditions in vitro, the loaded drug can be released in a minute under NIR irradiation, while liposomes maintain serum stability otherwise. This enables rapid laser‐induced drug release using remarkably low amounts of PoP (i.e., 0.3 molar percent). Light‐triggered drug release occurs concomitantly with DOPC and cholesterol oxidation, as detected by mass spectrometry. In the presence of an oxygen scavenger or an antioxidant, light‐triggered drug release is inhibited, suggesting that the mechanism is related to singlet oxygen mediated oxidization of unsaturated lipids. Despite the irreversible modification of lipid composition, DOPC‐containing PoP liposome permeabilization is transient. Human pancreatic xenograft growth in mice is significantly delayed with a single chemophototherapy treatment following intravenous administration of 6 mg kg^?1 doxorubicin, loaded in liposomes containing small amounts of DOPC and PoP.