Table 4.

Simplified core performance comparison of EVs’ engineering strategies

Engineering strategy	Targeting efficiency	Payload capacity	Release characteristics	Stability	Core advantages	Key limitations	Ref.
Surface-targeting modifications (e.g., peptide modification)	High (active targeting; 5–20x efficiency boost vs. unmodified EVs)	Moderate (additional drug-loading step required)	Rapid release (> 70% released in 1–6 h)	Moderate (in vivo half-life extended by 2–3x)	Precise targeting; suitable for systemic therapy	High modification difficulty; potential membrane damage	[162, 163]
Composite biomaterial carriers (e.g., hydrogel loading)	Moderate (strong local retention; poor systemic targeting)	High (3–10x payload increase; compatible with multiple drugs)	Controlled sustained release (> 7 days, two-phase release)	High (in vivo retention extended by 5–7x)	High payload; tunable release; safe for local long-term therapy	Unsuitable for systemic delivery; variable degradation rates	[164, 165]
Functionalized loading	Moderate (requires combination with targeting modifications)	High (supports synergistic multi-drug loading)	Controlled release (stimulus-responsive; leakage < 5%)	Moderate (enhanced membrane stability; potential immunogenicity)	High loading efficiency; synergistic/responsive delivery	Complex synthesis; higher cost	[166, 167]
Lyophilization	Moderate (> 90% retention with proper protectants)	Moderate (protects pre-loaded drugs; no direct loading function)	Consistent with fresh EVs (no inherent controlled release)	High (stable for 6–12 months at 4 °C/−20 °C)	Improves storage stability; facilitates clinical translation	Needs protectant optimization; high energy cost; requires combination with other strategies	[159, 161]