ELCA provides safe and effective adjunctive therapy in contemporary PCI to treat lesions associated with balloon failure due to an inability either to cross the lesion or to expand a balloon sufficiently to permit stenting. ELCA was successful in the majority of these selected cases when used independently with further effectiveness achieved when combined with RA or after RA failure.

These results suggest that despite conventional therapy, endogenous aldosterone can be an arrhythmogenic influence in patients with CAD, but without heart failure. The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure.

Desmoplasia is characteristic of pancreatic ductal adenocarcinoma (PDAC), which exhibits 5‐year survival rates of 3%. Desmoplasia presents physical and biochemical barriers that contribute to treatment resistance, yet depleting the stroma alone is unsuccessful and even detrimental to patient outcomes. This study is the first demonstration of targeted photoactivable multi‐inhibitor liposomes (TPMILs) that induce both photodynamic and chemotherapeutic tumor insult, while simultaneously remediating desmoplasia in orthotopic PDAC. TPMILs targeted with cetuximab (anti‐EGFR mAb) contain lipidated benzoporphyrin derivative (BPD‐PC) photosensitizer and irinotecan. The desmoplastic tumors comprise human PDAC cells and patient‐derived cancer‐associated fibroblasts. Upon photoactivation, the TPMILs induce 90% tumor growth inhibition at only 8.1% of the patient equivalent dose of nanoliposomal irinotecan (nal‐IRI). Without EGFR targeting, PMIL photoactivation is ineffective. TPMIL photoactivation is also sixfold more effective at inhibiting tumor growth than a cocktail of Visudyne‐photodynamic therapy (PDT) and nal‐IRI, and also doubles survival and extends progression‐free survival by greater than fivefold. Second harmonic generation imaging reveals that TPMIL photoactivation reduces collagen density by >90% and increases collagen nonalignment by >103‐fold. Collagen nonalignment correlates with a reduction in tumor burden and survival. This single‐construct phototoxic, chemotherapeutic, and desmoplasia‐remediating regimen offers unprecedented opportunities to substantially extend survival in patients with otherwise dismal prognoses.

With the continued development of nanomaterials over the past two decades, specialized photonanomedicines (light-activable nanomedicines, PNMs) have evolved to become excitable by alternative energy sources that typically penetrate tissue deeper than visible light. These sources include electromagnetic radiation lying outside the visible near-infrared spectrum, high energy particles, and acoustic waves, amongst others. Various direct activation mechanisms have leveraged unique facets of specialized nanomaterials, such as upconversion, scintillation, and radiosensitization, as well as several others, in order to activate PNMs. Other indirect activation mechanisms have leveraged the effect of the interaction of deeply penetrating energy sources with tissue in order to activate proximal PNMs. These indirect mechanisms include sonoluminescence and Cerenkov radiation. Such direct and indirect deep-tissue activation has been explored extensively in the preclinical setting to facilitate deep-tissue anticancer photodynamic therapy (PDT); however, clinical translation of these approaches is yet to be explored. This review provides a summary of the state of the art in deep-tissue excitation of PNMs and explores the translatability of such excitation mechanisms towards their clinical adoption. A special emphasis is placed on how current clinical instrumentation can be repurposed to achieve deep-tissue PDT with the mechanisms discussed in this review, thereby further expediting the translation of these highly promising strategies.

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