Cutaneous squamous cell carcinoma and malignant melanoma are two most typical malignant tumors in dermatology, of which the latter one has a lower incidence but higher malignancy. These cutaneous tumors usually occur at exposed skin, which usually requires non-invasive diagnosis and therapy, whereas conventional pathological diagnosis and surgical therapy are both invasive. With improvement of people's living standards, the need of an integrated and intelligent solution to non-invasive diagnosis and precision therapy is rising and the integration of medicine and engineering may provide the solution.

Recently, a research by Prof. Wang Xiuli from Shanghai Skin Disease Hospital affiliated to Tongji University and Prof. Zhang Binbo from Tongji University School of Medicine shows that, intelligent nanoprobes（iHRANPs）responsive to H₂O₂ can discriminate tumors of different types based on the H₂O₂ concentration difference inside tumors and therefore precisely guide subsequent therapy, achieving intelligent theranostics integrating photoacoustic diagnosis and photothermal therapy. This research was recently published in internationally renowned journal ACS Nano. 

On the basis of previous research, Prof. Wang Xiuli and her team applied theranostics nanoprobes to diagnosis and therapy of cutaneous squamous cell carcinoma and melanoma. Clinically, melanoma and cutaneous squamous cell carcinoma have different biological features, differing greatly in malignancy, which is closely associated with tumor microenvironment. H₂O₂ in tumor microenvironment are associated with occurrence, development and metastasis of tumor so that there might be difference of H₂O₂ concentration in different tumors. How to conduct precision therapy that is responsive to microenvironment？ Prof. Zhang Binbo's team synthesized a highly sensitive iHRANPs responsive to H₂O₂ by enzyme-mediated bionics. H₂O₂ triggers HRP to catalyze oxidation of ABTS to ABTS•+ that has a strong absorption of near infrared light and therefore the probe shows good photoacoustic and photothermal properties.

Figure 1 schematic of precision theranostics of cutaneous tumors by iHRANPs.

Prof. Wang Xiuli's team studied iHRANPs in cutaneous squamous cell carcinoma mice and melanoma mice contrastively. Results showed that after intravenous injection of iHRANPs through tail veins, photoacoustic signal in melanoma is stronger than that in cutaneous squamous cell carcinoma while magnetic resonance signal in both tumors increased but has no significant difference. These results indicate that H₂O₂ concentration is higher in melanoma than in cutaneous squamous cell carcinoma, as is also validated by both in vivo and in vitro quantitative test. iHRANPs show different responsiveness to different cutaneous tumors, as is verified by photoacoustic signals, laying the foundation of differential diagnosis of the two tumors. Subsequent photothermal experiments showed results consistent with above conclusion, in which tumor suppression in melanoma mice is stronger than that in cutaneous squamous cell carcinoma mice after intravenous injection of iHRANPs through tail veins and illumination of 808 nm light. In addition, topical injection of H₂O₂ in cutaneous squamous cell carcinoma increased photothermal tumor suppression of iHRANPs. Based on these results, we can use iHRANPs-mediated photothermal anti-tumor effect in precise therapy of melanoma and cutaneous squamous cell carcinoma and achieve magnetic resonance imaging of iHRANPs. This research preliminarily practiced the concept of non-invasive, precision therapy and integrated theranostics at the animal level and laid the foundation for further clinical translation of intelligent medicine.

This research received supports from Tongji University Interdisciplinary Project of Medicine and Engineering and National Natural Science Funds. The co-correspondence authors are Prof. Wang Xiuli and Prof. Zhang Binbo. The co-first authors are Dr. Wang Peiru from Department of Photomedicine Therapy, Dr. Yang Weitao and graduate student Shen Shuzhan from Tongji University School of Medicine.

Authors：Peiru Wang^#, Weitao Yang^#, Shuzhan Shen^#, Chao Wu, Long Wen, Qian Cheng, Bingbo Zhang^* and Xiuli Wang^*.

Link: Differential Diagnosis and Precision Therapy of Two Typical Malignant Cutaneous Tumors Leveraging Their Tumor Microenvironment: A Photomedicine Strategy. https://pubs.acs.org/doi/pdf/10.1021/acsnano.9b04070