Microneedle-Assisted Transdermal Delivery of 2D Bimetallic Metal-Organic Framework Nanosheet-Based Cascade Biocatalysts for Enhanced Catalytic Therapy of Melanoma.

Current conventional treatments for malignant melanoma still face limitations, especially low therapeutic efficacy and serious side effects, and more effective strategies are urgently needed to develop. Delivering biocatalysts into tumors to efficiently trigger in-situ cascade reactions has showed huge potential in producing more therapeutic species or generating stronger tumoricidal effects for augmented tumor therapy. Recently, ultrathin two-dimensional (2D) metal-organic framework (MOF) nanosheets have acquired great interests in biocatalysis owing to their large surface areas and abundant accessible active catalytic sites. Herein, we develop an enhanced catalytic therapeutic strategy against melanoma by biocompatible microneedle (MN)-assisted transdermal delivery of a 2D bimetallic MOF nanosheet-based cascade biocatalyst (Cu-TCPP(Fe)@GOD). Profiting from the constructed dissolving MN system, the loaded Cu-TCPP(Fe)@GOD hybrid nanosheets could be accurately delivered into the melanoma sites through skin barriers, and subsequently trigger the specific cascade catalytic reactions in response to the acidic tumor microenvironment (TME) to effectively generate highly toxic hydroxyl radical (•OH) and deplete glucose nutrient for inducing the death of melanoma cells. The ultimate results prove the high melanoma inhibition effect and biosafety of such therapeutic modality, exhibiting a new and promising strategy to conquer malignant melanoma. This article is protected by copyright. All rights reserved.