Engineered bacterial outer membrane vesicles enhance efficacy of phototreatment for skin cancer

On July 3, the research team led by Assoc. Prof. PENG Lihua and Prof. GAO Jianqing from the Zhejiang University College of Pharmaceutical Sciences published an open-access research article titled “Engineering bacterial outer membrane vesicles as transdermal nanoplatforms for photo-TRAIL-programmed therapy against melanoma” in the Science Advances.

Melanoma is a malignant tumor located at the interface of epidermis and dermis and marked by rapid progression, fast relapse, and high metastasis. Phototreatment, which is induced by the interaction of near-infrared (NIR) light and photosensitizer (PTS), such as indocyanine green (ICG) to ablate tumor spheroids, has been widely employed to treat skin melanoma. However, due to the finite penetration of NIR light and the poor specificity of PTS, the tumor masses at skin deep site and phototreatment margins frequently result in fast relapse and metastasis of melanoma. 

ZJU researchers engineer bacterial outer membrane vesicles (OMVs), which are derived from TRAIL gene transformed E. coli, modified by αvβ3 integrin targeting peptide and ICG into nanoplatforms (I-P-OMVs) for the transdermal TRAIL- and ICG-programmed delivery to skin melanoma. I-P-OMVs display remarkable SC penetration, reaching more than 400 μm beneath the skin surface and the superior targeting and infiltration in melanoma spheroids. Photo-TRAIL treatment induced by the topical application of I-P-OMVs+NIR delays the progression, relapse, and metastasis of skin melanoma with high efficiency. OMVs detoxified by lysozyme treatment are featured by superb biocompatibility without inducing any side effect or toxicity in mice.

This study provides a proof-of-concept design in engineering bacterial-derived OMVs into transdermal nanoplatforms for photo-TRAIL–programmed therapy, thereby circumventing the susceptibilities of proteins and PTS in conventional delivery strategies. Transdermal photo-TRAIL–programmed therapy not only performs remarkably in treating superficial cancers but also shows considerable potential for treating dermatological diseases, such as acne and nonmelanoma skin tumors that tend to cover a large area on the face, the head, or the neck, for which current delivery strategies are neither clinically justifiable nor effective. In addition, various proteins can be incorporated within OMVs as a cocktail therapy.