An NIR Discrete Metallacycle Constructed from Perylene Bisimide and Tetraphenylethylene Fluorophores for Imaging‐Guided Cancer Radio‐Chemotherapy

Abstract

To promote the clinical theranostic performances of platinum‐based anticancer drugs, imaging capability is urgently desired, and their chemotherapeutic efficacy needs to be upgraded. Herein, a theranostic metallacycle (M) is developed for imaging‐guided cancer radio‐chemotherapy using perylene bisimide fluorophore (PPy) and tetraphenylethylene‐based di‐Pt(II) organometallic precursor (TPE‐Pt) as building blocks. The formation of this discrete supramolecular coordination complex facilitates the encapsulation of M by a glutathione (GSH)‐responsive amphiphilic block copolymer to prepare M‐loaded nanoparticles (MNPs). TPE‐Pt acts as a chemotherapeutic drug and also an excellent radiosensitizer, thus incorporating radiotherapy into the nanomedicine to accelerate the therapeutic efficacy and overcome drug resistance. The NIR‐emission of PPy is employed to detect the intracellular delivery and tissue distribution of MNPs in real time. In vitro and in vivo investigations demonstrate the excellent anticancer efficacy combining chemotherapy and radiotherapy; the administration of this nanomedicine effectively inhibits the tumor growth and greatly extends the survival rate of cisplatin‐resistant A2780CIS‐tumor‐bearing mice. Guided by in vivo fluorescence imaging, radio‐chemotherapy is precisely carried out, which facilitates boosting of the therapeutic outcomes and minimizing undesired side effects. The success of this theranostic system brings new hope to supramolecular nanomedicines for their potential clinical translations.

Tumor Microenvironment—A Short Review of Cellular and Interaction Diversity

“…These include, inter alia, avoidance of recognition through the lack of expression of MHC class I (major histocompatibility complex) molecules, loss of antigenic epitopes, inactivation of immunological cells through the production of immunosuppressive factors, expression of anti-apoptotic proteins on cancer cells and a reduction in pro-apoptotic protein expression. A number of these mechanisms are conducive to progression, creation of their own environment for the development and closure of cells in their own favorable environment [ 3 , 4 , 5 ]. Therefore, understanding what happens within the tumor microenvironment and which mechanisms are responsible for tumor development and progression will let us know how cancer could protect itself against the immune system.…”

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

“…An example of a nanotheranostic concept is the use of tetraphenylethylene-based di-Pt(II) organometallic precursor (TPE-Pt), which is a chemotherapeutic with additional properties of a radiosensitizer, sensitizing cancer cells to radiotherapy. In vitro and in vivo studies in mice showed effective inhibition of tumor growth and prolonged survival of mice with cisplatin-resistant cancer [ 103 ]. In the context of CC treatment, there are promising reports using nanoparticles and small interfering RNA (siRNA), showing the ability to inhibit genes responsible for CC invasion and development [ 104 ].…”

Activatable “Matryoshka” nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer

“…Due to the complexity and heterogeneity of tumors, personalized treatment is a trend. A potential way to achieve it is theranostics, which combines treatment with real-time diagnosis to provide an opportunity to monitor the effectiveness of treatment and adjust the treatment window over time [ [74] , [75] , [76] ]. Due to its high depth penetration and spatial/temporal resolution, photoacoustic (PA) imaging can guide drug release, localization, and diagnosis [ 77 , 78 ].…”