Biphotonic photosensitizers, nanoparticles containing the same and their use as drugs

A method for preparing a silica nanoparticle composition comprising at least one silica nanoparticle comprising at least one compound used as a photosensitizer according to formula (I):

• wherein at least one of the Z1, Z2, Z3 or Z4 groups represents a group V, said group V being a molecular clip constituted by -α-β-δ wherein:
• α is a functional linking group and
• β is an alkyl chain, linear or branched, containing from 1 to 9 carbon atoms, and
• δ is a Si(OR′)3 group, wherein R′ is an alkyl chain, linear or branched, from 1 to 9 carbon atoms,
• said method comprising preparing a reaction mixture comprising at least one compound according to formula (I):
• wherein
• the groups A and B represent independently from each other —CH═CH—, or —C≡C—,
• the terms t, u, v, and w represent, independently from each other, values ranging from 0 to 9,
• the groups Y1 and Y2 represent independently from each other:
• a hydrogen atom, or
• an alkyl group linear, branched or substituted, carrying from 1 to 9 carbon atoms, or
• a polyethylene glycol chain of formula:
• —(CH2)n—O—(CH2CH2O)mCH3, wherein n<4 and m varies from 1 to 6, or
• an ammonium group of formula:
• —(CH2)p—NR3+X−, wherein X− is selec from the group consisting of halogens, tosylate, sulphate, phosphate, NTf2, and PF6 anions, provided said anion does not quench the fluorescence of the compound of formula (I), p varies from 1 to 6, and R is an alkyl chain linear or branched, from 1 to 9 carbon atoms,
• the groups Z1, Z2, Z3, and Z4 represent independently from each other:
• a hydrogen atom, or
• a group W, said group W being a chemically reactive group, or
• an aryl, aryloxy, aralkyl, aralkyloxy, heteroaryl, or heteroaryloxy group, ranging from 1 to 10 carbon atoms, containing a chemically reactive group W as above defined, or
• an alkyl chain possibly unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, or
• an alkyl chain possibly unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, and containing said chemically reactive group W, or
• a polyethylene glycol chain of formula —(CH2)q—O—(CH2CH2O)r—CH2CH2—W, wherein q<4 and r varies from 1 to 6, and W is said chemically reactive group,
• provided at least one of the Z1, Z2, Z3 or Z4 groups represents:
• said chemically reactive group W, or
• an aryl, aryloxy, aralkyl, aralkyloxy, heteroaryl, or heteroaryloxy group, ranging from 1 to 10 carbon atoms, containing said chemically reactive group W, or
• an alkyl chain possibly unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, and containing said chemically reactive group W, or
• a polyethylene glycol chain of formula —(CH2)q—O—(CH2CH2O)r—CH2CH2—W, wherein q<4 and r varies from 1 to 6, and W is said chemically reactive group,
• the groups Z5 and Z6 represent independently from each other:
• a hydrogen atom, or
• an alkyl chain possibly unsaturated, linear, branched or substituted, ranging from 1 to 9 carbon atoms, or
• an alkoxy group, a carbocyclic group, a heterocyclic group, an aromatic group, ranging from 1 to 9 carbon atoms, or
• Z5 and Z6 are linked together through an ethylene glycol group, thus providing a 3,4-ethylenedioxythiophene group (EDOT) with the thiophene group they are linked to,

A probe enabling the imaging of cancer cells comprising:

• (i) one compound of formula (I):
• wherein
• the groups A and B represent independently from each other —CH═CH—, or —C≡C—,
• the terms t, u, v, and w represent, independently from each other, values ranging from 0 to 9,
• the groups Y1 and Y2 represent independently from each other:
• a hydrogen atom, or
• an alkyl group linear, branched or substituted, carrying from 1 to 9 carbon atoms, or
• a polyethylene glycol chain of formula:
• —(CH2)n—O—(CH2CH2O)mCH3, wherein n<4 and m varies from 1 to 6, or
• an ammonium group of formula:
• —(CH2)p—NR3+X−, wherein X− is selected from the group consisting of halogens, tosylate, sulphate, phosphate, NTf2, and PF6 anions, provided said anion does not quench the fluorescence of the compound of formula (I), p varies from 1 to 6, and R is an alkyl chain linear or branched, from 1 to 9 carbon atoms,
• the groups Z1, Z2, Z3, and Z4 represent independently from each other:
• a hydrogen atom, or
• a group W, said group W being a chemically reactive group, or
• a group V, said group V being used as a molecular clip constituted by -α-β-δ, wherein:
• α is a functional linking group, and
• β is an alkyl chain, linear or branched, containing from 1 to 9 carbon atoms, and
• δ is a Si(OR′)3 group, wherein R′ is an alkyl chain, linear or branched, from 1 to 9 carbon atoms, or
• an aryl, aryloxy, aralkyl, aralkyloxy, heteroaryl, or heteroaryloxy group, ranging from 1 to 10 carbon atoms, containing said chemically reactive group W, or
• an alkyl chain optionally unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, or
• an alkyl chain optionally unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, and containing said chemically reactive group W, or
• a polyethylene glycol chain of formula —(CH2)q—O—(CH2CH2O)r—CH2CH2—W, wherein q<4 and r varies from 1 to 6, and W is said chemically reactive group,
• provided at least one of the Z1, Z2, Z3 or Z4 groups represents:
• said chemically reactive group W, or
• said group V being a molecular clip constituted by -α-β-δ, wherein:
• α is a functional linking group, and
• β is an alkyl chain, linear or branched, containing from 1 to 9 carbon atoms, and
• δ is a Si(OR′)3 group, wherein R′ is an alkyl chain, linear or branched, from 1 to 9 carbon atoms, or
• an aryl, aryloxy, aralkyl, aralkyloxy, heteroaryl, or heteroaryloxy group, ranging from 1 to 10 carbon atoms, containing said chemically reactive group W, or
• an alkyl chain optionally unsaturated, linear, branched or substituted, ranging from 1 to 10 carbon atoms, and containing said chemically reactive group W, or
• a polyethylene glycol chain of formula —(CH2)q—O—(CH2CH2O)r—CH2CH2—W, wherein q<4 and r varies from 1 to 6, and W is said chemically reactive chemically reactive group,
• the groups Z5 and Z6 represent independently from each other:
• a hydrogen atom, or
• an alkyl chain optionally unsaturated, linear, branched or substituted, ranging from 1 to 9 carbon atoms, or
• an alkoxy group, a carbocyclic group, a heterocyclic group, or an aromatic group, ranging from 1 to 9 carbon atoms, or
• Z5 and Z6 are linked together through an ethylene glycol group, thus providing a 3,4-ethylenedioxythiophene group (EDOT) with the thiophene group they are linked to,
• or
• (ii) at least one silica nanoparticle comprising at least one of said compound of formula (I).