Table 6.
Distinguished achievements and drawbacks of the BPs-functionalized drug delivery systems
| Drug delivery system type | Distinguished achievements | Unignorable drawbacks | Ref. |
|---|---|---|---|
| BP-Drug Conjugate (12b80/DOX) | Outstandingly sustained release profile, which improved therapeutic efficiency of the drug, successful modulation of linker degradation rate | Unsuccessful in decreasing tumour volume in vivo | [23] |
| BP-Drug Conjugate (BP15/ Pt(NO3)2(en)) | Selective accumulation in bone with higher metabolic activity | Limited worldwide availability of raw materials | [17] |
| BP-Drug Conjugate (BP22/BTZ) | Successful modulation of linker degradation rate, Serum stability, Delayed clearance from well-perfused bone marrow | - | [24] |
| Ca-based System (HAp/ALN/IBF) | Very high encapsulation efficiency despite the opposite nature of drug and carrier (hydrophobic/hydrophilic), which is achieved because of ALN | Huge burst release due to opposite nature of drug and carrier | [28] |
| Ca-based System (BG/HA/ALN/DOX) | Controlled degradation rate by addition of HA-ALN ligand and consequent control over release pattern | Despite the acid-sensitivity of BG NPs, around 50% of the drug was released in physiological pH as well | [30] |
| Inorganic Carbon-based Systems (GON/ALN/DOX) | Outstandingly high loading and encapsulation efficiency, Selective accumulation in tumour-bearing bone, High release sensitivity to pH | Similar in vitro cytotoxicity of free DOX and DOX@GON-ALN | [33] |
| Inorganic Carbon-based Systems (C60/HA/RGD/ALN/Ce6) | Capable of including multiple ligands with various functions, Significant therapeutic results in vivo and tumour volume reduction, successful circumvention of biocompatibility concerns of CQDs | Complex preparation procedure due to the presence of multiple ligands | [36] |
| Dendrimer (PAMAM/HA/ALN/DTX) | Sequential targeting of bone mineral matrix and cancerous cell receptor by a single ligand using a pH-sensitive linker | Significant burst release is anticipated in vivo due to the parallel sensitivity of nanostructure to reducing agents and pH | [54] |
| Albumin NP (Albumin/ALN/DOX) | Size stability in fetal bovine serum over time, Selective accumulation in tumour-bearing bone and clearance from other organs, Tumour-targeting functionality of albumin | Unsuccessful in decreasing tumour volume in vivo | [55] |
| Self-assembling System (PEG/ALN/PTX) | Biological half-life improved 4-fold compared with free drug | Significant accumulation in the kidney due to renal excretion | [56] |
| Self-assembling System (DOPE/CHEMS/DSPE/ALN/DOX) | Modifying NPs with ALN reduced nonspecific accumulation in the spleen and liver and doubled accumulation in the tumour | Increased accumulation in liver and spleen compared with free DOX | [57] |
| Self-assembling System (SPC/Cholesterol/HA/ALN/DOX) | Sequential targeting of bone mineral matrix and cancerous cell receptor by a single ligand using a redox-sensitive linker, Minimal systemic side effects are anticipated | Unsuccessful in decreasing tumour volume in vivo | [44] |
| Self-assembling System (HA/C18/ALN/CUR) | Very low CMC value and consequently high in vivo stability | Unsuccessful in decreasing tumour volume in vivo | [45] |
| Self-assembling System (DOPA/ZnPc/ALN/BTZ) | Successful inhibition of tumour growth in vivo | Unsuccessful in decreasing tumour volume in vivo | [47] |
| Multimodal System (BaTiO3 / Fe3O4/RIS) | Engineered to execute various modes of cancer therapy | Complex synthesis protocol | [58] |
| Metal-organic Frameworks (ZIF-8/ZOL) | Simple synthesis protocol with mild conditions enabling delivery of sensitive biological molecules | High burst release associated with the pH-sensitive nature of the ZIF-8 structure | [59] |
| PLGA NP (PLGA/ALN/ZOL/EPB/GCB/DOX/CXB) | High loading efficiency, Preservation of drug molecules from intracellular degradation, Prevention of quick efflux, Inhibition of burst release by the nanocarrier even under acidic conditions, Promising therapeutic results in vivo and reduced tumour volume | - | [51-53] |
| Self-assembling System (PIP-BP ionizable lipids) | An extensive library of piperazine-based bisphosphonate ionizable lipids were prepared which enabled targeted delivery to the bone microenvironment in vivo following systemic administration | The ring structure formed through cyclization may result in the random orientation of the bisphosphonate group on the surface of nanoparticles either outward or inward | [60] |
| BP-Drug Conjugate (Cy5.5-ALN) | In vitro and in vivo studies demonstrated that Cy5.5-ALN targets mineralized components of bone-forming tumours | No report of therapeutic efficiency evaluation with a small molecule drug | [61] |
| BP-Drug Conjugate () | The reactivity of the complexes with 5'-GMP, B- and G-quadruplex DNA models, and their cytotoxicity against a panel of human tumour cell lines was explored | No in vivo experiments were reported | [62] |
PAMAM: Polyamidoamine; DTX: Docetaxel; PTX: Paclitaxel; DOPE: Cholesteryl hemisuccinate; CHEMS: Dioleoyl phosphatidylethanolamine; DSPE: 1,2-distearoyl-sn-glycero-3- phosphoethanolamine; SPC: Soybean phosphatidylcholine; C18: Octadecanoic Acid; DOPA: Dioleoyl phosphatidic acid; RIS: Risedronate; ZIF-8: A metal-organic framework composed of Zn2+ ions and imidazolate ligands