Folate-Targeted Nanoliposomal Chemophototherapy.

Light-responsive liposomes have been developed for the on-demand release of drugs. However, efficient delivery of chemotherapeutic drugs to tumor for cancer theranostics remains a challenge. Herein, folic acid (FA), an established ligand for targeted drug delivery, was used to decorate light-sensitive porphyrin-phospholipid (PoP) liposomes, which were assessed for FA-targeted chemophototherapy (CPT).

Surfactant-Stripped Pheophytin Micelles for Multimodal Tumor Imaging and Photodynamic Therapy.

Porphyrin-based nanomaterials can inherently integrate multiple contrast imaging functionalities with phototherapeutic capabilities. We dispersed pheophytin (Pheo) into Pluronic F127 and carried out low-temperature surfactant-stripping to remove the bulk surfactant. Surfactant-stripped Pheo (ss-Pheo) micelles exhibited a similar size, but higher near-infrared fluorescence, compared to two other nanomaterials also with high porphyrin density (surfactant-stripped chlorophyll micelles and porphysomes).

Membrane Disruption by Very Long Chain Fatty Acids during Necroptosis.

Necroptosis is a form of regulated cell death which results in loss of plasma membrane integrity, release of intracellular contents, and an associated inflammatory response. We previously found that saturated very long chain fatty acids (VLCFAs), which contain ≥20 carbons, accumulate during necroptosis. Here, we show that genetic knockdown of Fatty Acid (FA) Elongase 7 (ELOVL7) reduces accumulation of specific very long chain FAs during necroptosis, resulting in reduced necroptotic cell death and membrane permeabilization.

Surfactant-Stripped Micelles for NIR-II Photoacoustic Imaging through 12 cm of Breast Tissue and Whole Human Breasts.

Surfactant-stripped micelles are formed from a commercially available cyanine fluoroalkylphosphate (CyFaP) salt dye and used for high contrast photoacoustic imaging (PAI) in the second near-infrared window (NIR-II). The co-loading of Coenzyme Q10 into surfactant-stripped CyFaP (ss-CyFaP) micelles improves yield, storage stability, and results in a peak absorption wavelength in the NIR-II window close to the 1064 nm output of Nd-YAG lasers used for PAI. Aqueous ss-CyFaP dispersions exhibit intense NIR-II optical absorption, calculated to be greater than 500 at 1064 nm.

Liposomal formulations of photosensitizers.

Photodynamic therapy (PDT) is a clinical ablation modality to treat cancers and other diseases. PDT involves administration of a photosensitizer, followed by irradiation of target tissue with light. As many photosensitizers are small and hydrophobic, solubilization approaches and nanoscale delivery vehicles have been extensively explored.

Loading and Releasing Ciprofloxacin in Photoactivatable Liposomes.

We demonstrate that ciprofloxacin can be actively loaded into liposomes that contain small amounts of porphyrin-phospholipid (PoP). PoP renders the liposomes photoactivatable, so that the antibiotic is released from the carrier under red light irradiation (665 nm). The use of 2 molar % PoP in the liposomes accommodated active loading of ciprofloxacin.

Binding of an amphiphilic phthalocyanine to pre-formed liposomes confers light-triggered cargo release.

Liposomes are able to load a range of cargos and have been used for drug delivery applications, including for stimuli-triggered drug release. Here, we describe an approach for imparting near infrared (NIR) light-triggered release to pre-formed liposomes, using a newly-synthesized cationic, amphiphilic phthalocyanine. When simply mixed in aqueous solution with cargo-loaded liposomes, the cationic amphiphilic phthalocyanine, but not a cationic hydrophilic azaphthalocyanine, spontaneously incorporates into the liposome bilayer.

Pharmacokinetics and pharmacodynamics of liposomal chemophototherapy with short drug-light intervals.

Chemophototherapy (CPT) merges photodynamic therapy with chemotherapy and can substantially enhance drug delivery. Using a singular liposomal formulation for CPT, we describe a semi-mechanistic pharmacokinetic-pharmacodynamic (PK/PD) model to investigate observed antitumor effects. Long-circulating, sterically-stabilized liposomes loaded with doxorubicin (Dox) stably incorporate small amounts of a porphyrin-phospholipid (PoP) photosensitizer in the bilayer.

A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging.

A multifunctional biodegradable brush polymer-drug conjugate (BPDC) is developed for the co-delivery of hydrophobic paclitaxel (PTX) and hydrophilic gemcitabine (GEM) chemotherapeutics, as well as a tumor imaging agent. A novel ternary copolymer of conventional, acetylenyl-functionalized and allyl-functionalized lactides is prepared to serve as the backbone precursor of BPDC. Acetylenyl groups of the copolymer are then reacted with poly(ethylene glycol) (PEG) side chains and cyanine5.

Blood Interactions, Pharmacokinetics, and Depth-Dependent Ablation of Rat Mammary Tumors with Photoactivatable, Liposomal Doxorubicin.

Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with antitumor synergy between chemo- and photocomponents. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays.

A malaria vaccine adjuvant based on recombinant antigen binding to liposomes.

Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt porphyrin-phospholipid, resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly orientated display via his-tag insertion in the cobalt porphyrin-phospholipid bilayer, without covalent modification or disruption of antigen conformation.

Short Drug-Light Intervals Improve Liposomal Chemophototherapy in Mice Bearing MIA PaCa-2 Xenografts.

Chemophototherapy (CPT) is an emerging tumor treatment that combines phototherapy and chemotherapy. Long-circulating (LC) liposomes can stably incorporate 2 mol % porphyrin-phospholipid (PoP) in the bilayer and load doxorubicin (Dox) to generate LC-Dox-PoP liposomes, for single-agent CPT. Following intravenous administration to mice, LC-Dox-PoP liposomes (2 mg/kg Dox) circulated with similar blood concentration ranges produced by a typical human clinical dose of DOXIL (50 mg/m Dox).

Multicolor Liposome Mixtures for Selective and Selectable Cargo Release.

Many approaches exist for stimuli-triggered cargo release from nanocarriers, but few can provide for on-demand release of multiple payloads, selectively. Here, we report the synthesis of purpurin-phospholipid (Pur-P), a lipid chromophore that has near-infrared absorbance red-shifted by 30 nm compared to a structurally similar pyropheophorbide-phospholipid (Pyr-P). Liposomes containing small amounts of either Pur-P or Pyr-P exhibited similar physical properties and fluorescence self-quenching.

Intrabilayer Cu Labeling of Photoactivatable, Doxorubicin-Loaded Stealth Liposomes.

Doxorubicin (Dox)-loaded stealth liposomes (similar to those in clinical use) can incorporate small amounts of porphyrin-phospholipid (PoP) to enable chemophototherapy (CPT). PoP is also an intrinsic and intrabilayer Cu chelator, although how radiolabeling impacts drug delivery has not yet been assessed. Here, we show that Cu can radiolabel the stable bilayer of preformed Dox-loaded PoP liposomes with inclusion of 1% ethanol without inducing drug leakage.