Doxorubicin encapsulated in stealth liposomes conferred with light-triggered drug release

Abstract

Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Inclusion of 2 molar % porphyrin-phospholipid (PoP) imparted optimal near infrared (NIR) light-triggered release of doxorubicin (Dox) from conventional sterically stabilized stealth liposomes. The type and amount of PoP affected drug loading, serum stability and drug release induced by NIR light. Cholesterol and PEGylation were required for Dox loading, but slowed light-triggered release. Dox in stealth PoP liposomes had a long circulation half-life in mice of 21.9 hours and was stable in storage for months. Following intravenous injection and NIR irradiation, Dox deposition increased ~7 fold in treated subcutaneous human pancreatic xenografts. Phototreatment induced mild tumor heating and complex tumor hemodynamics. A single chemophototherapy treatment with Dox-loaded stealth PoP liposomes (at 5–7 mg/kg Dox) eradicated tumors while corresponding chemo- or photodynamic therapies were ineffective. A low dose 3 mg/kg Dox phototreatment with stealth PoP liposomes was more effective than a maximum tolerated dose of free (7 mg/kg) or conventional long-circulating liposomal Dox (21 mg/kg). To our knowledge, Dox-loaded stealth PoP liposomes represent the first reported long-circulating nanoparticle capable of light-triggered drug release.

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

“…To address this, PoP liposomes comprising of Pyro‐lipid rather than HPPH‐lipid were developed 209. A 2 mol.% quantity of Pyro‐lipid imparted the light‐triggered capability of conventional liposomes, while 5 mol.% PEG‐lipid enable the long circulation of Dox‐loaded PoP liposomes (Dox‐PoP liposomes).…”

Rethinking translational nanomedicine: insights from the ‘bottom-up’ design of the Porphysome for guiding the clinical development of imageable nanomaterials

“…For instance, a NIR lighttriggered membrane permeabilization phenomena [15 ] has been achieved in long-circulating liposomal doxorubicin formulations with the modest titration of HPPHlipid [15 ,35] or Pyro-lipid [36] into those formulations. It was reported that the inclusion of as little as 5-10 mol.% HPPH-lipid or 2 mol.% Pyro-lipid was needed for the spatially and temporally controlled release of entrapped doxorubicin with laser irradiation in vivo [35,36].…”

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

“…The stimuli-sensitive nanocarriers maintain their stealth function throughout circulation, and upon arrival at the specific tumor site, undergo rapid changes, such as aggregation, disruption, and permeability changes, which trigger drug release when exposed to a particular tumor microenvironment [2,52,53]. In order to achieve site-specific triggered drug release, several strategies have been investigated, for example, internal stimuli that are characteristic for a tumor microenvironment (low pH, redox potential, high temperature, and enzymes) and external stimuli, such as magnetic fields, ultrasound, or light [54][55][56]. Both internal and external stimuli-sensitive liposomes will be addressed further, classified according to the mechanism exploited.…”