Table 2.

Advantages and Disadvantages of Major Classes of Nano-Based Drug Delivery Systems and Their Current Clinical Status for Breast Cancer Treatment

	Advantages	Disadvantages	Clinically Evaluated Examples for Breast Cancer Treatment	References
Organic Nano-based Drug Delivery Systems
Carbon-based Nanocarriers	-Electrical and thermal conductivity -Mechanical strength -Optical properties -Structural diversity -Large surface area -High chemical stability -Preferential tumour accumulation -High cellular entry	-Inherent toxicities	-Activated carbon nanoparticle-epirubicin suspension ●N/A	[46–49]
Dendrimers	-Precise molecular weight -Biocompatibility -Monodispersity -High aqueous solubility -High biological barrier penetrability -Polyvalency for versatile functionalisation	-Cationic dendrimers ●Toxicities	-PEGylated PLL dendrimer-based nanoformulation of docetaxel (DEP® docetaxel) ●Phase II -PEGylated PLL dendrimer-based nanoformulation of SN-38 (DEP® irinotecan) ●Phase II	[50,52,56–58]
Lipid-based Nanocarriers	-Ease of preparation -Large-scale and low-cost production -Biocompatibility -Biodegradability -Targetability -High stability -High drug loading capacity -Capability to incorporate both hydrophobic and hydrophilic drugs	-Liposomes ●Difficulties with large-scale manufacturing, sterilisation and stability -Niosomes ●Polydispersity of currently commercially available non-ionic surfactants -Solid lipid nanoparticles ●Low drug loading capacity and risk of drug expulsion	-PEGylated liposomal doxorubicin (Doxil®) ●Approved -Liposomal cytarabine (Depocyt®) ●Approved; Phase III for leptomeningeal metastasis from breast cancer	[59–61,63–69,78]
Polymer-based Nanocarriers	-Natural polymers ●Better biocompatibility and biodegradability -Synthetic polymers ●Abundantly present ●Better thermal stability and mechanical properties ●Can be more easily processed to achieve desired pore size and scaffold geometry	-Natural polymers ●Poor thermal stability and mechanical properties -Synthetic polymers ●Impurities that can affect biocompatibility	-mPEG-PDLLA micellar formulation of paclitaxel (Genexol-PM®) ●Approved -PGA-paclitaxel (Opaxio™) ●Phase III; Phase II for metastatic breast cancer	[81,82,87–90]
Protein-based Nanocarriers	-Biocompatibility -Biodegradability -Easy synthesis and nanoparticle size control -Cost-effectiveness -High stability -Amenability to surface modification	-Albumin ●High cost -Collagen ●Risk of prion transmission from animal sources -Ferritin ●High cost -Gelatin ●Risk of prion transmission from animal sources ●Low mechanical strength ●Fast degradation -Gliadin ●Fast degradation ●Large nanoparticle size -Legumin ●Low yield -Protamine ●Low yield -Silk protein fibroin ●Slow degradation -Silk protein sericin ●Low yield	-Nanoparticle albumin-bound paclitaxel (Abraxane®) ●Approved -Nanoparticle albumin-bound rapamycin (ABI-009) ●Phase II; Phase I for advanced breast cancer	[93,94,96–100]
Inorganic Nano-based Drug Delivery Systems
Metallic Nanoparticles	-Unique catalytic, electrical, magnetic, optical and thermal properties -Simple surface chemistry and functionalisation -Easy synthesis -High drug loading capacity -Large surface area-to-volume ratio	-Toxicities -Low stability -Low biocompatibility	-Colloidal gold-bound tumour necrosis factor (Aurimune™) ●Phase I	[39,102,107,109–111]
Mesoporous Silica Nanoparticles	-Simple fabrication -Tunable particle size and shape -Large internal pore volume and surface area -High drug loading capacity -Good stability -Good biocompatibility -Easy surface modification and functionalisation -Capability to incorporate both hydrophilic and hydrophobic drugs	-Toxicities	-N/A	[112–115,121–123]

Abbreviation: mPEG-PDLLA, monomethoxy-poly(ethylene glycol)-block-poly(D,L-lactide).