Porphyrin modified telodendrimers
AssigneeThe Regents of the University of California
InventorsKit S. Lam, Yuanpei Li, Chong-Xian Pan
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Abstract
The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics.
Claims21
A nanocarrier having an interior and an exterior, the nanocarrier comprising a plurality of first conjugates wherein each conjugate is a compound of formula (I):
- wherein:
- each PEG is a polyethyleneglycol (PEG) polymer having a molecular weight of 1-100 kDa;
- A comprises at least one branched monomer unit X and is linked to at least one PEG group;
- X is independently selected from the group consisting of 2,3-diamino propanoic acid, 2,4-diaminobutanoic acid, 2,5-diaminopentanoic acid (ornithine), 2,6-diaminohexanoic acid (lysine), (2-Aminoethyl)-cysteine, 3-amino-2-aminomethyl propanoic acid, 3-amino-2-aminomethyl-2-methyl propanoic acid, 4-amino-2-(2-aminoethyl) butyric acid and 5-amino-2-(3-aminopropyl) pentanoic acid;
- each Y2 is absent or a crosslinking group independently selected from the group consisting of boronic acid, dihydroxybenzene and a thiol, wherein at least two crosslinking groups are present:
- each L2 is independently a bond or a linker;
- and
- each R is independently selected from the group consisting of cholic acid, (3α, 5β, 7α, 12α)-7,12-dihydroxy-3-(2,3-dihydroxy-1-propoxy)-cholic acid (CA-4OH), (3α, 5β, 7α, 12α)-7-hydroxy-3,12-di(2,3-dihydroxy-1-propoxy)-cholic acid (CA-5OH), (3α, 5β, 7α, 12α)-7,12-dihydroxy-3-(3-amino-2-hydroxy-1-propoxy)-cholic acid (CA-3OH—NH2), cholesterol formate, doxorubicin, rhein, and porphyrin,
- wherein at least one R group is a porphyrin,
- wherein each conjugate self-assembles in an aqueous solvent to form the nanocarrier such that a hydrophobic pocket is formed in the interior of the nanocarrier by the orientation of the hydrophobic face of each amphiphilic compound towards each other, wherein the PEG of each conjugate self-assembles on the exterior of the nanocarrier.
Dependencies are inferred from the claim text.