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Despite tremendous advances in gas therapy, there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug delivery. ...Second near-infrared (NIR-II) window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive nature. In this study, we engineered an NIR-II laser-activated theranostic agent (named CP-bF@PEG) that was composed of amphiphilic polymers (Pluronic F127, with polyethylene glycol, PEG, moieties) coated with an NIR-II-absorbing conjugated polymer (PTTBBT, CP) and nitric oxide (NO) donor (benzofuroxan, bF), which served as an NIR-II photothermal inducer and NO nanogenerator. Under deep tissue penetration of NIR-II laser irradiation, CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal effect. Moreover, CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable manner. This NIR-II-absorbing polymer for high-contrast NIR-II fluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy, as evidenced by pronounced tumor therapeutic efficacy and few side effects. This nanotheranostic agent is a highly promising candidate for high-contrast NIR-II imaging-guided precision photothermal therapy combined with gas therapy against cancer.
Polyphenols, the phenolic hydroxyl group‐containing organic molecules, are widely found in natural plants and have shown beneficial effects on human health. Recently, polyphenol‐containing ...nanoparticles have attracted extensive research attention due to their antioxidation property, anticancer activity, and universal adherent affinity, and thus have shown great promise in the preparation, stabilization, and modification of multifunctional nanoassemblies for bioimaging, therapeutic delivery, and other biomedical applications. Additionally, the metal−polyphenol networks, formed by the coordination interactions between polyphenols and metal ions, have been used to prepare an important class of polyphenol‐containing nanoparticles for surface modification, bioimaging, drug delivery, and disease treatments. By focusing on the interactions between polyphenols and different materials (e.g., metal ions, inorganic materials, polymers, proteins, and nucleic acids), a comprehensive review on the synthesis and properties of the polyphenol‐containing nanoparticles is provided. Moreover, the remarkable versatility of polyphenol‐containing nanoparticles in different biomedical applications, including biodetection, multimodal bioimaging, protein and gene delivery, bone repair, antibiosis, and cancer theranostics is also demonstrated. Finally, the challenges faced by future research regarding the polyphenol‐containing nanoparticles are discussed.
The synthesis, properties, and biomedical applications of polyphenol‐containing nanomaterials are comprehensively reviewed. The problems in the current polyphenol‐based nanosystems and the future research directions in this field are also discussed.
Recently, lanthanide nanoparticles have aroused widespread interest in cancer theranostics by virtue of their excellent photoresponsive performance in deep‐seated tumors. The abundant ladder‐like ...energy levels, controllable emission profiles, and unique photoluminescence properties make lanthanide nanoparticles highly efficient for deep skin‐penetration of near‐infrared (NIR) light, concentrating light energy in tumors with negligible scattering and minimal autofluorescence from biological tissues. High‐Z radio‐sensitization of lanthanide elements endows lanthanide nanoparticles with a high X‐ray attenuation coefficient, making them effective nanoprobes for X‐ray‐excited bioimaging and synchronous radiotherapy‐related treatments. In this review, comprehensive progressions including the synthesis, structural characteristics of lanthanide nanoparticles, and distinct optical excitation mechanisms with NIR and X‐ray triggers, are summarized. Advances in NIR‐excited and X‐ray‐triggered cancer imaging methods and therapies are described in detail, wherein NIR‐induced luminescence from upconversion nanoparticles and downconversion nanoparticles are introduced separately based on some typical sensitization. Finally, the challenges and opportunities of lanthanide nanoparticles as light‐triggered cancer theranostic candidates are discussed, whose translation from bench to bedside still has a long journey to go.
This review summarizes and discusses the on‐going efforts in optimizing lanthanide nanoparticles to respond to high skin‐penetration near‐infrared (NIR) and X‐ray stimuli, achieving high‐resolution imaging and precise spatiotemporal treatment of deep‐seated/untouchable tumors. Concurrently, orientations from basic concepts, distinct optical conversion mechanisms, to practical merits of NIR/X‐ray‐excited lanthanide nanoparticles have been introduced to facilitate the comprehensive understanding of deep‐seated tumor treatment.
Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) ...such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.
To integrate photodynamic therapy (PDT) with photothermal therapy (PTT) and chemotherapy for enhanced antitumor efficiency, we developed a mild and rational route to synthesize novel multifunctional ...GdOF:Ln@SiO2 (Ln = 10%Yb/1%Er/4%Mn) mesoporous capsules using strong up-conversion luminescent (UCL) GdOF:Ln as cores and mesoporous silica layer as shells, followed by modification with varied functional groups onto the framework. It was found that due to the codoped Yb/Er/Mn in GdOF, the markedly enhanced red emission can efficiently transfer energy to the conjugated PDT agent (ZnPc) which produces high singlet oxygen, and the incorporated carbon dots outside the shell can generate obvious thermal effect under 980 nm laser irradiation and also prevent the premature leaking of ZnPc. Simultaneously, the as-produced thermal effect can obviously enhance the doxorubicin (DOX) release, which greatly improves the chemotherapy, resulting in a synergistic therapeutic effect. The system exhibits drastically enhanced therapeutic efficiency against tumor growth, as demonstrated both in vitro and in vivo. Especially, the doped rare earth ions in the host endow the material with excellent UCL imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging properties, thus realizing the target of multimodal imaging guided multiple therapies.
Photothermal agents with absorption in the second near‐infrared (NIR‐II) biowindow have attracted increasing attention for photothermal therapy (PTT) on account of their deeper tissue penetration ...capacity. However, most of the current NIR‐II photothermal agents exhibit low photothermal conversion efficiency (PCE) and long‐term biotoxicity. To overcome these shortcomings, herein, nickel and nitrogen co‐doped carbon dots (Ni‐CDs, ≈4.6 nm) are prepared via a facile one‐pot hydrothermal approach for imaging‐guided PTT in the NIR‐II window. The Ni‐CDs exhibit significant absorption in the NIR‐II region with a distinguished PCE as high as 76.1% (1064 nm) and have excellent photostability and biocompatibility. Furthermore, the Ni‐CDs can be employed as photothermal, photoacoustic, and magnetic resonance imaging contrast agents because of their outstanding photothermal effect and instinctive paramagnetic feature. The Ni‐CDs demonstrate significant PTT efficacy of tumor upon 1064 nm irradiation with a low power density (0.5 W cm−2). The Ni‐CDs can be eliminated from the body via a renal filtration pathway, thereby minimizing their long‐term biotoxicity. Therefore, this work provides a simple and feasible approach to develop photothermal agents with remarkable PCE in the NIR‐II region, presenting good biosafety for multimodal imaging‐guided PTT of tumor.
Renal‐clearable nickel‐doped carbon dots (Ni‐CDs) with boosted photothermal conversion efficiency (76.1%) in the second near‐infrared region are developed using a facile one‐pot hydrothermal method. Benefiting from the outstanding photothermal effect, excellent solubility/dispersity in water, good biosafety, and instinctive paramagnetic feature, the Ni‐CDs could serve as a promising photothermal agent for multimodal imaging‐guided photothermal therapy for tumors.
Tumor-derived exosome can suppress dendritic cells (DCs) and T cells functions. Excessive secretion of exosomal programmed death-ligand 1 (PD-L1) results in therapeutic resistance to PD-1/PD-L1 ...immunotherapy and clinical failure. Restored T cells by antiexosomal PD-L1 tactic can intensify ferroptosis of tumor cells and vice versa. Diminishing exosomal suppression and establishing a nexus of antiexosomal PD-L1 and ferroptosis may rescue the discouraging antitumor immunity. Here, we engineered phototheranostic metal-phenolic networks (PFG MPNs) by an assembly of semiconductor polymers encapsulating ferroptosis inducer (Fe3+) and exosome inhibitor (GW4869). The PFG MPNs elicited superior near-infrared II fluorescence/photoacoustic imaging tracking performance for a precise photothermal therapy (PTT). PTT-augmented immunogenic cell death relieved exosomal silencing on DC maturation. GW4869 mediated PD-L1 based exosomal inhibition revitalized T cells and enhanced the ferroptosis. This novel synergy of PTT with antiexosomal PD-L1 enhanced ferroptosis evoked potent antitumor immunity in B16F10 tumors and immunological memory against metastatic tumors in lymph nodes.
Abstract To integrate biological imaging and multimodal therapies into one platform for enhanced anti-cancer efficacy, we have designed a novel core/shell structured nano-theranostic by conjugating ...photosensitive Au 25SR 18 – (SR refers to thiolate) clusters, pH/temperature-responsive polymer P(NIPAm-MAA), and anti-cancer drug ( doxorubicin, DOX ) onto the surface of mesoporous silica coated core–shell up-conversion nanoparticles (UCNPs). It is found that the photodynamic therapy (PDT) derived from the generated reactive oxygen species and the photothermal therapy (PTT) arising from the photothermal effect can be simultaneously triggered by a single 980 nm near infrared (NIR) light. Furthermore, the thermal effect can also stimulate the pH/temperature sensitive polymer in the cancer sites, thus realizing the targeted and controllable DOX release. The combined PDT, PTT and pH/temperature responsive chemo-therapy can markedly improve the therapeutic efficacy, which has been confirmed by both in intro and in vivo assays. Moreover, the doped rare earths endow the platform with dual-modal up-conversion luminescent (UCL) and computer tomography (CT) imaging properties, thus achieving the target of imaging-guided synergistic therapy under by a single NIR light.
Although chemotherapy has the potential to induce tumor immunotherapy via immunogenic cell death (ICD) effects, how to control the intensity of the immune responses still deserves further ...exploration. Herein, a controllable ultrasound (US)‐triggered chemo‐immunotherapy nanoagonist is successfully synthesized by utilizing the pH and reactive oxygen species (ROS) dual‐responsive PEG‐polyphenol to assemble sonosensitizer zinc oxide (ZnO) and doxorubicin (DOX). The PZnO@DOX nanoparticles have an intelligent disassembly to release DOX and zinc ions in acidic pH conditions. Notably, US irradiation generates ROS by sonodynamic therapy and accelerates the drug release process. Interestingly, after the PZnO@DOX+US treatment, the injured cells release double‐stranded DNA (dsDNA) from the nucleus and mitochondria into the cytosol. Subsequently, both the dsDNA and zinc ions bind with cyclic GMP‐AMP synthase and activate the stimulator of interferon genes (STING) pathway, resulting in the dendritic cell maturation, ultimately promoting DOX‐induced ICD effects and antigen‐specific T cell immunity. Therefore, chemotherapy‐induced immune responses can be modulated by non‐invasive control of US.
The PZnO@DOX nanoparticles can release zinc ions and doxorubicin in the tumor microenvironment with controllable ultrasound and demonstrate substantial antitumor capacity by enhancing immunogenic cell death effects through stimulation of the interferon genes pathway. This combination strategy involving chemotherapy, sonodynamic therapy, and immunotherapy significantly inhibits tumor growth, metastasis, and recurrence both in vitro and in vivo.
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