Table 1.
Summary of physical strategies for EPR-adaptive delivery
Technique | Physiological Effect | Strengths | Weaknesses |
---|---|---|---|
Radiation | Decreased intratumoral and interstitial fluid pressure, reduced perfusion, alteration of ECM and vessel growth | Established therapeutic benefit, fits clinical workflow, high penetration depth, utilizes existing clinical resources | Radiation dose and fractionation schedule must be optimized for different tumor types to prevent delivery impairment, damage to surrounding tissue |
Ultrasound | Transient disruption of endothelium increases vascular permeability | High penetration depth, non-invasive, localized, minimal damage to surrounding tissue, amenable to repeated treatments, can use existing clinically-approved microbubbles | Some strategies require image guidance, some techniques are not compatible with current clinical ultrasound systems |
Hyperthermia | Vasodilation, increased vessel permeability | Versatile modes of delivery, potentially non-invasive, localized, exploitable side-effect of other external stimuli | Delivery resistance after repeat sessions, size limitations on eligible sensitizing agents |
Photodynamic Therapy | Damage to vessels causes transient vascular leakiness | Co-registration of photosensitizer and applied light gives high specificity to area of illumination, potentially non-invasive | Low penetration depth of light necessitates superficial targets or invasive light delivery probes, delay required for photosensitizer build-up before light administration extends clinical burden |