Table 3 Factors affecting nanocarrier biodistribution

Size and shape

Blood flow rate and vessel permeability

Half-life and clearance rate

Tumor perfusion and oxygenation

Intravenous, intratumoral, intraperitoneal, etc

[105]

Surface charge and coating

Lymphatic drainage and lymph node accumulation

Protein binding and opsonization

Extracellular matrix and cell adhesion molecules

Oral, nasal, pulmonary, transdermal, etc

[106]

Surface functionalization

Plasma protein corona and immune system response

Blood–brain barrier penetration

pH and redox gradients

Local, regional, systemic, etc

[106]

Drug payload and release mechanism

Renal and hepatic function

Tissue-specific accumulation and clearance

Cellular uptake and trafficking

Active targeting, passive targeting, etc

[106, 107]

Biodegradability and toxicity

Interstitial fluid pressure and flow

Cellular metabolism and excretion

Tumor heterogeneity and evolution

Single dose, repeated dose, etc

[56, 108]

Shape stability

Inflammatory response and cytokine release

Vascular permeability and leakiness

Stromal cells and immune cells

Direct injection, inhalation, etc

[109]

Aggregation and stability

Oxygen and carbon dioxide transport

Extravasation and interstitial diffusion

Hypoxia and acidity

Local hyperthermia, phototherapy, etc

[84]

Magnetism and targeting

Enzyme activity and expression

Receptor density and internalization

Angiogenesis and lymphangiogenesis

Ultrasound, magnetic, etc

[110]

Encapsulation and surface modification

Protease activity and inhibition

Immune checkpoint expression and regulation

Immunosuppression and immunostimulation

Combination, alternating, etc

[109]

Controlled release and activation

Nutrient and oxygen deprivation

Apoptosis and necrosis

Resistance and tolerance

Adjuvant therapy, radiation, etc

[45]