During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

The return of a forgotten polymer : Polycaprolactone in the 21st century

Recent progress of chemodynamic therapy-induced combination cancer therapy

Afterglow imaging with long-lasting luminescence after cessation of light excitation provides opportunities for ultrasensitive molecular imaging; however, the lack of biologically compatible afterglow agents has impeded exploitation in clinical settings. This study presents a generic approach to transforming ordinary optical agents (including fluorescent polymers, dyes, and inorganic semiconductors) into afterglow luminescent nanoparticles (ALNPs). This approach integrates a cascade photoreaction into a single-particle entity, enabling ALNPs to chemically store photoenergy and spontaneously decay it in an energy-relay process. Not only can the afterglow profiles of ALNPs be finetuned to afford emission from visible to near-infrared (NIR) region, but also their intensities can be predicted by a mathematical model. The representative NIR ALNPs permit rapid detection of tumors in living mice with a signal-to-background ratio that is more than three orders of magnitude higher than that of NIR fluorescence. The biodegradability of the ALNPs further heightens their potential for ultrasensitive in vivo imaging. Afterglow luminescence is used to reduce background noise and increase sensitivity; however, biocompatible afterglow materials are limited. Here, the authors report on an approach to turn standard optical agents into afterglow nanoparticles and demonstrate the application in tumour imagining in vivo.

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A generic approach towards afterglow luminescent nanoparticles for ultrasensitive in vivo imaging.

Nanotheranostic agents of gold nanomaterials in the second near-infrared (NIR-II) window have attracted significant attention in cancer management, owing to the reduced background signal and deeper penetration depth in tissues. However, it is still challenging to modulate the localized surface plasmon resonance (LSPR) of gold nanomaterials from the first near-infrared (NIR-I) to NIR-II region. Herein, a plasmonic modulation strategy of gold nanorods (GNRs) through manganese dioxide coating is developed for NIR-II photoacoustic/magnetic resonance (MR) duplex-imaging-guided NIR-II photothermal chemodynamic therapy. GNRs are coated with silica dioxide (SiO2 ) and then covered with magnesium dioxide (MnO2 ) to obtain the final product of GNR@SiO2 @MnO2 (denoted as GSM). The LSPR peak of GNRs could be tuned by adjusting the thickness of the MnO2 layer. Theoretical simulations reveal that this plasmonic modulation is mainly due to the change of refraction index around the GNRs after coating with the MnO2 layer. Additionally, the MnO2 layer is demonstrated to degrade into Mn2+ ions in response to peroxide and acidic protons in the tumor microenvironment, which allows for MR imaging and chemodynamic therapy. This plasmonic modulation strategy can be adapted to other metal nanomaterials and the construction of a new class of NIR-II nanotheranostics.

Manganese‐Dioxide‐Coating‐Instructed Plasmonic Modulation of Gold Nanorods for Activatable Duplex‐Imaging‐Guided NIR‐II Photothermal‐Chemodynamic Therapy

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co-workers in 2016. Recently, with the rapid development of Fenton and Fenton-like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe-involved CDT strategies, the Fenton-like reaction-mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials-involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances.

Manganese-based nanomaterials have piqued great interest in cancer nanotheranostics, owing to their excellent physicochemical properties. Here we report a facile wet-chemical synthesis of size-controllable, biodegradable, and metastable γ-phase manganese sulfide nanotheranostics, which is employed for tumor pH-responsive traceable gas therapy primed chemodynamic therapy (CDT), using bovine serum albumin (BSA) as a biological template (The final product was denoted as MnS@BSA). The as-prepared MnS@BSA can be degraded in response to the mildly acidic tumor microenvironment, releasing hydrogen sulfide (H2S) for gas therapy and manganese ions for magnetic resonance imaging (MRI) and CDT. In vitro experiments validated the pH-responsiveness of MnS@BSA at pH 6.8 and both H2S gas and •OH radicals were detected during its degradation. In vivo experiments showed efficiently tumor turn-on T1-weighted MRI, significantly suppressed tumor growth and greatly prolonged survival of tumor-bearing mice following intravenous administration of MnS@BSA. Our findings indicated that MnS@BSA nanotheranostics hold great potential for traceable H2S gas therapy primed CDT of cancer.

Tumor pH-responsive metastable-phase manganese sulfide nanotheranostics for traceable hydrogen sulfide gas therapy primed chemodynamic therapy.

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy. 

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In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy

Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to abundant reactive oxygen species (ROS). Owing to the multi-enzymatic activity and broad-spectrum ROS scavenging capacity of ceria nanoparticles (ceria NPs), herein, we report ultrasmall citric acid modified ceria nanozymes (3-4 nm) as antioxidants to alleviate rhabdomyolysis-induced AKI through removing excessive ROS. The as-prepared ceria NPs exhibited multi-enzymatic properties such as peroxidase, catalase, and superoxide dismutase, offering efficient protection of renal cells against H2O2 stimulation in vitro. Moreover, due to their ultrasmall size, ceria NPs could efficiently accumulate in the kidneys, thus protecting renal cells against ROS in vivo. Our results present ultrasmall ceria nanozymes as antioxidants for rhabdomyolysis-induced AKI alleviation, which shows great potential in clinic.

Shan Lei

Papers

Tumor pH-responsive metastable-phase manganese sulfide nanotheranostics for traceable hydrogen sulfide gas therapy primed chemodynamic therapy.

In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy

Ceria Nanozymes with Preferential Renal Uptake for Acute Kidney Injury Alleviation.

Multi-enzyme mimetic ultrasmall iridium nanozymes as reactive oxygen/nitrogen species scavengers for acute kidney injury management.

Ultrasmall platinum nanozymes as broad-spectrum antioxidants for theranostic application in acute kidney injury