Recent advances in near-infrared-II hollow nanoplatforms for photothermal-based cancer treatment.

Near-infrared-II (NIR-II, 1000-1700 nm) light-triggered photothermal therapy (PTT) has been regarded as a promising candidate for cancer treatment, but PTT alone often fails to achieve satisfactory curative outcomes. Hollow nanoplatforms prove to be attractive in the biomedical field owing to the merits including good biocompatibility, intrinsic physical-chemical nature and unique hollow structures, etc. On one hand, hollow nanoplatforms themselves can be NIR-II photothermal agents (PTAs), the cavities of which are able to carry diverse therapeutic units to realize multi-modal therapies. On the other hand, NIR-II PTAs are capable of decorating on the surface to combine with the functions of components encapsulated inside the hollow nanoplatforms for synergistic cancer treatment. Notably, PTAs generally can serve as good photoacoustic imaging (PAI) contrast agents (CAs), which means such kind of hollow nanoplatforms are also expected to be multifunctional all-in-one nanotheranostics. In this review, the recent advances of NIR-II hollow nanoplatforms for single-modal PTT, dual-modal PTT/photodynamic therapy (PDT), PTT/chemotherapy, PTT/catalytic therapy and PTT/gas therapy as well as multi-modal PTT/chemodynamic therapy (CDT)/chemotherapy, PTT/chemo/gene therapy and PTT/PDT/CDT/starvation therapy (ST)/immunotherapy are summarized for the first time. Before these, the typical synthetic strategies for hollow structures are presented, and lastly, potential challenges and perspectives related to these novel paradigms for future research and clinical translation are discussed.

MOF(Fe)-derived composites as a unique nanoplatform for chemo-photodynamic tumor therapy.

Fe-based metal-organic frameworks (MOFs) can be used for chemodynamic therapy (CDT) for tumors due to their unique Fenton-like effects and porous and biodegradable nature. The adsorption and transport of small molecule drugs by their structure has attracted much attention. Herein, MnO2@NH2-MIL101(Fe)@Ce6-F127 nanoparticles (MNMCF NPs) were synthesized using a facile solvothermal strategy. The small molecule photosensitizer Ce6 was adsorbed by MOFs to improve the biocompatibility of Ce6 and give it high bioavailability when injected intravenously. When the MNMCF NPs reached the tumor site, Fe-based MOFs exhibited Fenton-like properties, producing ˙OH and showing CDT effects. MnO2 could specifically respond to produce O2 in a tumor microenvironment, thereby improving the tumor hypoxia state and enhancing the efficacy of photodynamic therapy (PDT) by Ce6. Both the in vitro and in vivo experiments showed that the MNMCF-guided CDT/PDT combination therapy could effectively ablate tumors without the drawbacks of poor tolerability and potential long-term side effects. Therefore, the prepared MNMCF NPs can be used as promising candidates for synergistic CDT/PDT tumor therapy.

Manganese-based hollow nanoplatforms for MR imaging-guided cancer therapies.

Theranostic nanoplatforms integrating diagnostic and therapeutic functions have received considerable attention in the past decade. Among them, hollow manganese (Mn)-based nanoplatforms are superior since they combine the advantages of hollow structures and the intrinsic theranostic features of Mn2+. Specifically, the hollow cavity can encapsulate a variety of small-molecule drugs, such as chemotherapeutic agents, photosensitizers and photothermal agents, for chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), respectively. After degradation in the tumor microenvironment (TME), the released Mn2+ is able to act simultaneously as a magnetic resonance (MR) imaging contrast agent (CA) and as a Fenton-like agent for chemodynamic therapy (CDT). More importantly, synergistic treatment outcomes can be realized by reasonable and optimized design of the hollow nanosystems. This review summarizes various Mn-based hollow nanoplatforms, including hollow MnxOy, hollow matrix-supported MnxOy, hollow Mn-doped nanoparticles, hollow Mn complex-based nanoparticles, hollow Mn-cobalt (Co)-based nanoparticles, and hollow Mn-iron (Fe)-based nanoparticles, for MR imaging-guided cancer therapies. Finally, we discuss the potential obstacles and perspectives of these hollow Mn-based nanotheranostics for translational applications. Mn-based hollow nanoplatforms such as hollow MnxOy nanoparticles, hollow matrix-supported MnxOy nanoparticles, Mn-doped hollow nanoparticles, Mn complex-based hollow nanoparticles, hollow Mn-Co-based nanoparticles and hollow Mn-Fe-based nanoparticles show great promise in cancer theranostics.

A Nanoarchitectonic Approach Enables Triple Modal Synergistic Therapies To Enhance Antitumor Effects.

Improvement of antitumor effects relies on the development of biocompatible nanomaterials and combination of various therapies to produce synergistic effects and avoid resistance. In this work, we developed GBD-Fe, a nanoformulation that effectively integrated chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT). GBD-Fe used gold nanorods as photothermal agents and encapsulated doxorubicin to amplify Fe3+-guided CDT effects by producing H2O2 and reducing the intracellular glutathione levels. In vitro and in vivo experiments were conducted to demonstrate the enhanced accumulation and antitumor effects of this tripronged therapy under magnetic resonance imaging (MRI) guidance. This tripronged approach of CT/CDT/PTT effectively induced tumor cytotoxicity and inhibited tumor growth in tumor-bearing mice and therefore represents a promising strategy to effectively treat tumors.

Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.

Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.

Development of copper vacancy defects in a silver-doped CuS nanoplatform for high-efficiency photothermal-chemodynamic synergistic antitumor therapy.

The combination of chemodynamic and photothermal materials can not only improve the therapeutic effect of chemodynamic therapy (CDT) by thermal stimulation, but also play a synergistic therapeutic role. Benefitting from the strong near-infrared absorption ability, copper sulfide (CuS) nanomaterials are widely used in photothermal therapy. However, due to the harsh preparation conditions, low photothermal efficiency and poor biocompatibility, further biomedical application is limited. In this work, silver-doped copper sulfide nanoparticles (BSA-Ag:CuS) were synthesized using a biomineralization strategy using bovine serum albumin (BSA) as a template and stabilizer. Silver doping greatly improved the near-infrared absorption and photothermal efficiency of CuS nanoparticles, which can be used for 1064 nm laser-guided photothermal therapy (PTT). Meanwhile, BSA-Ag:CuS nanoparticles had a synergistic therapeutic effect with CDT and thus showed excellent antitumor performance. In vivo and in vitro biological experiments have shown that BSA-Ag:CuS nanoparticles have good stability, low toxicity, good biocompatibility and strong antitumor ability, and are promising as antitumor agents for future clinical cancer treatment.

Polydopamine-Based Tumor-Targeted Multifunctional Reagents for Computer Tomography/Fluorescence Dual-Mode Bioimaging-Guided Photothermal Therapy.

Development of multifunctional diagnosis and treatment reagents is very meaningful in clinical application. Herein, we developed a polydopamine-based (PDA-based) tumor targeted multifunctional reagent by surface-initiated atom transfer radical polymerization (ATRP) strategy. First, the targeted PDA nanoparticles were prepared via combining with folic acid (FA) and dopamine. Then ATRP technology was used to graft the europium(III) complexes onto PDA surface (defined as FEDA). A series of detections revealed that the FEDA nanoparticles had been successfully prepared and exhibited a bright X-ray computer tomography (CT) and photoluminescence (PL) dual-mode imaging efficiency and an excellent photothermal therapy (PTT) effect in vivo/in vitro.

Green Preparation of Straw Fiber Reinforced Hydrolyzed Soy Protein Isolate/Urea/Formaldehyde Composites for Biocomposite Flower Pots Application.

The effects of soil burial on the biodegradation of biocomposite flower pots (BFP) made from straw fiber (SF) and hydrolyzed soy protein isolate/urea/formaldehyde (HSPI/U/F) copolymer resin were studied in detail. The microstructure, crystallinity, functional groups, mechanical, degradation and thermal property of the prepared SF with HSPI/U/F copolymer resin have been studied, and the degradation mechanism was also elucidated. XRD results showed that the bond breakage between SF and HSPI/U/F copolymer resin induced a decrease in relative degradation-resistant crystal structures. FTIR spectra showed that the methylolated HSPI units could form a cross-linking network with U/F and SF. The BFP degradation after soil burial was mainly attributed to the effects of microorganisms. The degradation products were environmentally friendly, because they were degradable and could fertilize the soil. In addition, the U/F adhesives were slightly degraded by the microorganisms due to the HSPI in the pots. The TG and DSC results showed that the molecular motion of the BFP matrix could be restricted by the degradation action and the content of HSPI, resulting in decreased crystallization enthalpy and showing good thermal property. The tensile strength of different reinforced samples was not significantly reduced in comparison to U/F resin, and still kept good mechanical performance. Thus, the prepared SF reinforced HSPI/U/F copolymer resins could have good potential for use in the field of biodegradable flower pots because of their good thermal property, mechanical property, biodegradability, and relatively low cost.

A Novel Fluorescent Biosensor for Adenosine Triphosphate Detection Based on a Metal⁻Organic Framework Coating Polydopamine Layer.

In this work, a novel and sensitive fluorescent biosensor based on polydopamine coated Zr-based metal⁻organic framework (PDA/UiO-66) is presented for adenosine triphosphate (ATP) detection. This PDA/UiO-66 nanoparticle which holds a great potential to be excellent fluorescence quencher can protect the 6-carboxyfluorescein (FAM)-labeled probe from cleaved by DNase I dispersed in solution and the flurescence of labeled FAM is quenched. When ATP molecules exist, aptamers on the PDA/UiO-66 nanoparticles can hybridize with ATP molecule to form complex structure that will be desorbed from the PDA/UiO-66 and digested by DNase I. After that, the released ATP molecule can react with another aptamer on the PDA/UiO-66 complexes, then restarts a new cycle. Herein, the excellent strong fluorescence quenching ability and uploading more amount of aptamer probes of PDA/UiO-66 composites make them efficient biosensors, leading to a high sensitivity with detection limit of 35 nM. Compared with ATP detection directly by UiO-66-based method, the LOD is about 5.7 times higher with PDA/UiO-66 nanoparticle. Moreover, the enhanced biocompatibility and bioactivity with PDA layer of the composites render a proposed strategy for clinical diagnosis field of detecting small biological molecules in vivo in the future.