Differential Diagnosis and Precision Therapy of Two Typical Malignant Cutaneous Tumors Leveraging Their Tumor Microenvironment: A Photomedicine Strategy

Abstract

Elevated hydrogen peroxide (H2O2) in biological tissues is generally recognized to be relevant to the carcinogenesis process that regulates the proliferative activity of cancer cells and the transformation of malignant features. Inspired by this observation, it can be hypothesized that imaging H2O2 in the tumor microenvironment (TME) could help diagnose tumor types and malignancy, and even guide precise therapy. Thus, in this study, a noninvasive photomedicine strategy is demonstrated that leverages the different levels of H2O2 in the TME, and two representative skin cancers, malignant melanoma (MM, clinically higher incidence of metastasis and recurrence) and cutaneous squamous cell carcinoma (cSCC, relatively less dangerous), are differentially diagnosed. The working probe used here is one we previously developed, namely, intelligent H2O2 responsive ABTS-loaded HRP@Gd nanoprobes (iHRANPs). In this study, iHRANPs have advantages over ratiometric imaging due to their bimodal imaging elements, in which the inherent magnetic resonance imaging (MR) mode can be used as the internal imaging reference and the H2O2 responsive photoacoustic (PA) imaging modality can be used for differential diagnosis. Results showed that after intravenous injection of iHRANPs, the tumor signals on both MM and cSCC are obviously enhanced without significant difference under the MR modality. However, under the PA modality, MM and cSCC can be easily distinguished with obvious variations in signal enhancement. Particularly, guided by PA imaging, photothermal therapy (PTT) can be precisely applied on MM, and a strong antitumor effect was achieved owing to the excessive H2O2 in the TME of MM. Furthermore, exogenous H2O2 was injected into cSCC to remedy H2O2 deficiency in the TME of cSCC, and an evident therapeutic efficacy on cSCC can also be realized. This study demonstrated that MM can be differentially diagnosed from cSCC by noninvasive imaging of H2O2 in the TME with iHRANPs; meanwhile, it further enabled imaging-guided precision PTT ablation, even for those unsatisfactory tumor types (cSCC) through exogenously delivering H2O2.

Dissolving Microneedles with Spatiotemporally controlled pulsatile release Nanosystem for Synergistic Chemo-photothermal Therapy of Melanoma

“…Skin cancers represent a growing proportion of all human cancers and are associated with high mortality 1 . Although it only accounts for 4% of all skin cancer cases, malignant melanoma is the main cause of death in superficial skin tumors 2 , 3 .…”

Dual Ratiometric SERS and Photoacoustic Core–Satellite Nanoprobe for Quantitatively Visualizing Hydrogen Peroxide in Inflammation and Cancer

“…Moreover, the ratio SERS intensity of I 2228 /I 1418 in the tumor was much lower than that of the ratio SERS intensity in the normal (Figure 3 e), suggesting a higher level of H 2 O 2 in the tumor. The concentration of H 2 O 2 was determined to be 44.13±3.04 μ m in the tumors [26] . When PA and SERS imaging were performed at the same time point after intratumoral injection of nanoprobe, the nanoprobe responded quickly to the H 2 O 2 and the ratiometric PA and SERS intensity reached the plateau at 2 h (Figure S17 and Movies 1 and 2).…”

“…Thec oncentration of H 2 O 2 was determined to be 44.13 AE 3.04 mm in the tumors. [26] When PA and SERS imaging Figure 3. Schematic illustration of a) using ratiometric PA imaging and b) ratiometric SERS mapping to detect H 2 O 2 in the subcutaneous tumors of mice.…”

Nano-Medicine for Thrombosis: A Precise Diagnosis and Treatment Strategy

“…However, most of the nano-agents accumulate in liver and other organs, and the strategies might be limited to a specific type of thrombosis. Many efforts have been made to microenvironment-responsive contrast agents for cancer detection [ 54 – 56 ], and the effects are also appropriate for thrombosis diagnosis. Thrombin-activatable peptide, which can only be cleaved by thrombin, is a good choice for a thrombosis-responsive imaging system.…”