The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.

Conjugates comprising a drug, cell or biological molecule bound to a photoluminescent polymer nanoparticle, in particular a cross-linked polyfluorene nanoparticle, are described herein, as well as their methods of manufacture and their uses in biological imaging and sensing applications.

A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:

##STR00001##

wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO.sub.3H, —PO.sub.3H, —OH, —NH.sub.2, and -halogen; wherein Y.sub.1 and Y.sub.2 is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH.sub.2, SH and OH; and R.sub.3 and R.sub.4 are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.

A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:

##STR00001##

wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO.sub.3H, —PO.sub.3H, —OH, —NH.sub.2, and -halogen; wherein Y.sub.1 and Y.sub.2 is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH.sub.2, SH and OH; and R.sub.3 and R.sub.4 are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.

The present invention describes novel 7-alkylamino-3-(thienyl) coumarin fluorescent dyes of formula (I)

##STR00001##

These dyes are water soluble, can be excited by the 405 nm excitation source and exhibit a large Stokes shift (≧80 nm). Furthermore, the dyes possess a reactive group for the labeling of biomolecules or other analytes.

The disclosure relates to carrier particle-drug conjugates, including nanoparticle drug conjugates (NDC), that can be used in the delivery of a drug to a biological target (e.g., for targeted delivery of a cytotoxic drug to a cancer cell or tumor). Also disclosed are self-immolative linkers and linker-payload conjugates suitable for use in a carrier particle drug conjugate, and methods of making the same, and methods for treating cancer.

The invention provides a novel class of materials that possess triplet-triplet annihilation upconversion, compositions and methods of preparation and use thereof. The invention also relates to use of such materials and nanoparticles, for example, in stimulus-responsive, in situ delivery of biologically active agents.

The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.

The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.

The disclosure relates to nanoparticle drug conjugates (NDC) that comprise ultrasmall nanoparticles, folate receptor (FR) targeting ligands, and linker-drug conjugates, and methods of making and using them to treat cancer.