Polymersomes incorporating highly emissive probes
AssigneeThe Trustees of the University of Pennsylvania
InventorsDaniel A. Hammer, Michael J. Therien, Paiman Peter Ghoroghchian
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Abstract
The instant invention concerns compositions comprising polymersomes, visible or near infrared emissive agents, and optionally a targeting moiety associated with a surface of the polymersome. The invention also relates to use of these compositions in the treatment of disease and in imaging methodology.
Claims142
A polymersome comprising:
- (i) a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- and
- (ii) at least one visible- or near infrared-emissive agent that is dispersed within the polymersome membrane, where said emissive agent emits light in the 700-1100 nm spectral regime and where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety.
The polymersome of 7, wherein the said emissive agent comprises a meso-to-meso ethyne- or butadiyne-bridged linkage topology, said imaging agent being capable of emitting in the 700-to-1100 nm spectral regime.
A polymersome comprising:
- (i) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (ii) at least one emissive agent that emits light at a wavelength between 700-1100 where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and
- (iii) at least one targeting moiety associated with a surface of the polymersome.
A method of delivering an agent to a biological situs in a tissue or organism comprising administering to the tissue or organism a polymersome having the agent and comprising (a) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (b) at least one emissive agent which emits light at a wavelength between 700-1100 nm where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and (c) at least one targeting moiety associated with a surface of the polymersome.
A method of ascertaining the presence or absence of a disease state in an organism or tissue comprising:
- administering a polymersome to a patient, the polymersome comprising (a) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (b) at least one emissive agent that emits light at a wavelength between 700-1100 nm where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and (c) at least one targeting moiety associated with a surface of the polymersome;
- providing an instrument optically coupled to a light source, a light detector, or both, and
- operating the instrument to monitor the amount or distribution of the phorphinato imaging agent within the organism or tissue.
An in vivo method of diagnostics or imaging comprising:
- contacting a polymersome with tissue within an organism, the polymersome comprising (a) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (b) at least one emissive agent that emits light at a wavelength between 700-1100 nm where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and (c) at least one targeting moiety associated with a surface of the polymersome;
- providing an instrument optically coupled to a light source, a light detector, or both, and
- using the instrument to monitor the amount of the polymersome at a situs within the tissue.
An in vitro diagnostic method comprising:
- contacting a polymersome with isolated cells, mixtures of cells, or specific cell lines, with the polymersome comprising (a) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (b) at least one emissive agent that is dispersed within the polymersome membrane, at least one that emits light at a wavelength between 700-1100 nm where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and (c) at least one targeting moiety associated with a surface of the polymersome;
- providing an instrument optically coupled to a light source, a light detector, or both, and
- using the instrument to monitor cell-surface-to-polymersome binding.
A method for histological labeling, molecular classification of cell surface markers, or guiding the development of novel directed therapeutic strategies, comprising
- contacting a polymersome with isolated cells, mixtures of cells, or specific cell lines, with the polymersome comprising (a) a membrane comprising a plurality of amphiphilic copolymers comprising amphiphilic block copolymers that comprise at least one hydrophilic polymer bonded to at least one hydrophobic polymer;
- (b) at least one emissive agent that is dispersed within the polymersome membrane, at least one that emits light at a wavelength between 700-1100 nm where said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, said compound exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- and (c) at least one targeting moiety associated with a surface of the polymersome;
- providing an instrument optically coupled to a light source, a light detector, or both, and
- using the instrument to monitor cell-surface-to-polymersome binding.
A method of modulating the emission properties of a visible- or near infrared-emissive agent, wherein said emissive agent emits light in the 700-1100 nm spectral regime and wherein said emissive agent is an emissive conjugated compound comprising at least two covalently bound moieties;
- whereby upon exposing said compound to an energy source for a time and under conditions effective to cause said compound to emit light that at a wavelength between 700-1100 nm, and exhibits an integral emission oscillator strength that is greater than the emission oscillator strength manifest by either one of the said moieties individually;
- wherein said emissive agent comprises at least two porphyrin moieties, said porphyrin moieties being linked by a hydrocarbon bridge comprising at least one unsaturated moiety;
- said emissive agent being within a polymeric material, wherein at least one of the bound moieties comprises an ancillary substituent, the size and chemical constitution of said substituent being selected to provide said modulation.
Dependencies are inferred from the claim text.