Differential
Diagnosis and Precision Therapy of Two
Typical Malignant Cutaneous Tumors Leveraging Their Tumor Microenvironment:
A Photomedicine Strategy
Peiru Wang
Weitao Yang
Shuzhan Shen
Chao Wu
Long Wen
Qian Cheng
Bingbo Zhang
Xiuli Wang
10.1021/acsnano.9b04070.s001
https://acs.figshare.com/articles/journal_contribution/Differential_Diagnosis_and_Precision_Therapy_of_Two_Typical_Malignant_Cutaneous_Tumors_Leveraging_Their_Tumor_Microenvironment_A_Photomedicine_Strategy/9963737
Elevated
hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in the TME of MM. Furthermore, exogenous H<sub>2</sub>O<sub>2</sub> was injected into cSCC to remedy H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in the TME with iHRANPs; meanwhile, it further enabled imaging-guided
precision PTT ablation, even for those unsatisfactory tumor types
(cSCC) through exogenously delivering H<sub>2</sub>O<sub>2</sub>.
2019-10-10 14:03:21
remedy H 2 O 2 deficiency
HRP
Photomedicine Strategy Elevated hydrogen peroxide
imaging-guided precision PTT ablation
representative skin cancers
PA
cSCC
H 2 O 2
MM
MR
bimodal imaging elements
TME
imaging H 2 O 2
tumor types
iHRANP
Typical Malignant Cutaneous Tumors Leveraging
exogenous H 2 O 2
modality
noninvasive photomedicine strategy