Table 3.
Structural details and targeting efficiency of BP-drug conjugate systems
| Drug name | Bisphosphonate name | Type of conjugation | BPs position**** | Outcome | Ref. |
|---|---|---|---|---|---|
| Doxorubicin (DOX) | Alendronate | Hydrazone bond | Outside | Highly efficient bone targeting in vitro and in vivo | [20] |
| 5-Fluorodeoxyuridine (5F) | Alendronate | Non-cleavable covalent bond | Outside | Low therapeutic impact due to non-cleavable linker | [21] |
| Platinum isopropyl amine (PtC3) | Alendronate / Pamidronate | Chelation by P=O arms | Outside | PMD targeting function maintained after conjugation | [22] |
| Palladium II | Alendronate | Ionic conjugation | Within | More than 95 % binding to HAp in vitro | [19] |
| Pt(NO3)2(en) | BP-15* | Ionic conjugation | Within | Selective accumulation in hard tissues over soft tissues | [17] |
| Pt(NO3)2(en) | BP-15 | Ionic conjugation | Within | Selective accumulation in hard tissues over soft tissues | [18] |
| DOX | 12b80** | Hydrazone bond | Outside | Highly efficient bone targeting in vitro and in vivo | [23] |
| Bortezomib (BTZ) | BP-22*** | Boronate ester bond | Outside | No direct bone affinity assay, biological tests support effective bone targeting | [24] |
* (BP15): 2-amino-1-hydroxyethane-1,1-diyl-bisphosphonate
** (12b80): DOX-conjugated BP-21
*** (BP-22): 2-(bis(2-hydroxyethyl)amino)ethyl(bis(diethoxyphosphoryl)methyl)carbamate
**** (BPs Position): the position of the BPs in the bisphosphonate-drug complex has been reported as either ‘outside network’ or ‘within network’