Photoactivatable nanoparticles and uses thereof as agents for immunotherapy combinations
AssigneeBoard of Regents, The University of Texas System
InventorsGirgis Obaid, Nimit Shah, Nikita Kulkarni
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Abstract
Lipid nanoparticles described herein are useful in photodynamic therapy (PDT), a light-activated cancer treatment that uses photosensitizers (PSs) to generate reactive oxygen species (ROS), leading to tumor cell death. These lipid nanoparticles are capable of producing varying levels of oxygen-based radicals and singlet oxygen. In preferred embodiments, the lipid nanoparticles are verteporfin-lipid nanoparticles. Fine-tuning design features of the lipid nanoparticles, such as Type I ROS generation and predominantly ER and mitochondrial localization, provides a more robust induction of immunogenic cell death (ICD).
Claims25
Photoactivatable nanoparticles for use as therapeutic agents in immunotherapy treatments, comprising:
- lipid nanoparticles, wherein the lipid nanoparticles are liposomes or solid lipid nanoparticles, and wherein the lipid nanoparticles comprise phospholipids and lipids bound to polyethylene glycol;
- and
- photosensitizers incorporated within the nanoparticles, wherein the photosensitizers are benzoporphyrin derivative or chemical variants of benzoporphyrin derivative, and wherein the photoactivatable nanoparticles generate reactive oxygen species through light activation of the photosensitizer.
A method for immunotherapy in a subject, comprising:
- delivering photoactivatable nanoparticles to cancer cells of the subject for use as therapeutic agents, wherein the photoactivatable nanoparticles comprise lipid nanoparticles and photosensitizers incorporated within the lipid nanoparticles, wherein the lipid nanoparticles are liposomes or solid lipid nanoparticles, wherein the lipid nanoparticles comprise phospholipids and lipids bound to polyethylene glycol, wherein the photosensitizers are benzoporphyrin derivative or chemical variants of benzoporphyrin derivative;
- and
- activating the photosensitizers though light activation, whereby the photoactivatable nanoparticles generate reactive oxygen species and induce immunogenic cell death in the cancer cells.
A method for designing photoactivatable nanoparticles having enhanced activity as therapeutic agents, comprising:
- using data-driven statistical tool or unsupervised machine learning algorithm to evaluate properties and attributes of photoactivatable nanoparticles and produce evaluation results, wherein the properties and attributes comprise photophysical and photochemical properties;
- using the evaluation results of the Principal Component Analysis to predict relationships between the properties and attributes of the various photoactivatable nanoparticles and efficiency properties of the various photoactivatable nanoparticles, wherein the efficiency properties comprise subcellular localization, type of ROS generation, and induction of immunogenic cell death markers;
- and
- designing photoactivable nanoparticles having optimized efficiency properties and enhanced activity as therapeutic agents.
A method for enhancing immune cell infiltration and reducing immunosuppression in a subject, comprising:
- delivering photoactivatable nanoparticles to cancer tissue of the subject for use as therapeutic agents, wherein the photoactivatable nanoparticles comprise lipid nanoparticles and photosensitizers incorporated within the lipid nanoparticles, wherein the lipid nanoparticles are liposomes or solid lipid nanoparticles, wherein the lipid nanoparticles comprise phospholipids and lipids bound to polyethylene glycol, wherein the photosensitizers are benzoporphyrin derivative or chemical variants of benzoporphyrin derivative;
- and
- activating the photosensitizers through light activation, whereby the photoactivatable nanoparticles generate reactive oxygen species and enhance immune cell infiltration and reduce immunosuppression in the subject.
Dependencies are inferred from the claim text.