Aminopeptidase‐N‐activated Theranostic Prodrug for NIR Tracking of Local Tumor Chemotherapy

Abstract

The development of molecular theranostic prodrugs for in vivo cancer diagnosis and targeted chemotherapy is urgently required. Enzyme-activated prodrugs display superior selectivity as a result of cancer-specific enzymes which serve as cancer biomarkers. Herein, an aminopeptidase N (APN)activated theranostic prodrug Nile blue-C 6 -amide-p-fluorophenylalanyl-lmelphalanyl (NBFMel) is reported for fluorescence cancer diagnosis and local tumor treatment. NBFMel demonstrates negligible cytotoxicity and very weak fluorescence due to the photoinduced electron transfer (PET) between melphalan and Nile blue fluorophore. After activation caused by APN, the prodrug releases free melphalan that inhibits tumor cell growth. Simultaneously, the reaction blocks the PET process and switches on the fluorescence, which can be used for cancer diagnosis. NBFMel is successfully utilized to report the presence of tumor and for in situ tracking of drug release in tumor-bearing mouse models. Moreover, NBFMel demonstrates efficient tumor inhibition when intravenously injected into mice. Therefore, the APN-activated theranostic prodrug provides a new platform for in vivo cancer diagnosis and targeted anticancer chemotherapy.

Hypoxia-activated NIR photosensitizer anchoring in the mitochondria for photodynamic therapy

“…In recent decades, cancer has gradually become the major cause of death in both developed and less developed countries due to the growth and aging of the population and the incidence rate is increasing every year. 1,2 Therefore, multiple treatments including radiotherapy, 3,4 chemotherapy, 5,6 immunotherapy, 7,8 photothermal therapy (PTT), 9,10 photodynamic therapy (PDT) [11][12][13][14] and so on have been developed for treating cancer. Among them, photodynamic therapy has attracted great interest due to its minimal invasiveness, negligible drug resistance, controllable treatment area selection and excellent therapeutic effects.…”

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…However, some tissues, such as inflammatory tissues, also feature low‐pH environments, and BODIPY nano‐photosensitizers may generate phototoxicity toward nontumor tissues. Thus, BODIPY nano‐photosensitizers that are responsive to more specific tumor microenvironment markers such as enzymes are expected to be designed for highly specific cancer phototherapy …”

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

“…The drug administration at high doses causes several problems, such as low therapeutic efficiency and acute side effect to normally tissues . To address these challenges, some of molecular prodrugs are recently developed to enhance the selectivity for diseased cells and tissues and improve the therapeutic efficacy . Despite several advantages of this strategy, complicated process of prodrug design and preparation is required .…”

“…To address these challenges, some of molecular prodrugs are recently developed to enhance the selectivity for diseased cells and tissues and improve the therapeutic efficacy . Despite several advantages of this strategy, complicated process of prodrug design and preparation is required . More importantly, special drug modification is necessary for an individual drug and different diseases, which makes it hard to obtain a uniform procedure for the development of the prodrug strategy.…”