Prostate specific membrane antigen (PSMA) targeted nanoparticles for therapy of prostate cancer

A nanoparticle composition of formula I:

• (X)m—(Y)n—Z (I);
• wherein
• X is an organic small molecule PSMA inhibitor having a formula:
• wherein:
• R1 is optionally substituted alkylene, optionally substituted alkenylene, or optionally substituted alkynylene, each containing 0, 1, 2, or 3 heteroatoms selected from O or N;
• optionally substituted arylene, optionally substituted arylalkylene, optionally substituted heteroarylene, optionally substituted heterocyclic, or optionally substituted carbocyclic;
• R2 is optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl, optionally substituted arylalkyl, optionally substituted alkoxy, optionally substituted heteroaryl, optionally substituted heterocyclic, optionally substituted alkylcarboxy, or optionally substituted carbocyclic;
• R′ and R″ are each independently —OR4, —SR4, —SOR4, —SO2R4, N(R3)S(O)2—R4, —N(R3)(SO2)NR3R4, —NR3R4, —C(O)—O—R4, —C(O)R4, —C(O)NR3R4, or —N(R3)C(O)R4;
• R3 and R4 are each independently selected at each occurrence from the following:
• H, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• optionally substituted heterocyclic;
• or optionally substituted carbocyclic;
• Y is an organic linker having a formula
• wherein A is O, S, NH, N(alkyl) or N(aryl);
• and
• RA is —(CH2)r-Q-;
• Q is CO, C(O)O, C(O)NH, C(O)NRB, OCO, OC(O)O, OC(O)NH, OC(O)NRB, NHCO, NHC(O)O, NHC(O)NH, NHC(O)NRB, NRBCO, NRBC(O)O, NRBC(O)NH, NRBC(O)NRB, CS, C(S)O, C(S)NH, C(S)NRB, OCS, OC(S)O, OC(S)NH, OC(S)NRB, NHCS, NHC(S)O, NHC(S)NH, NHC(S)NRB, NRBCS, NRBC(S)O, NRBC(S)NH, NRBC(S)NRB;
• each RB is independently optionally substituted alkyl or optionally substituted aryl;
• and
• r is 3-20;
• Z is a nanoparticle comprising a biologically active agent and a fluorescein;
• m is 1-1000 and
• n is 1-1000.