Single-walled carbon nanohorns-based smart nanotheranostic: From phototherapy to enzyme-activated fluorescence imaging-guided photodynamic therapy.

Phototheranostics, a local non-invasive approach that integrates light-based diagnostics and therapeutics, enables precise treatment using nanotheranostic agents with minimal damage to normal tissues. However, ensuring high-efficiency ablation of cancer cells using phototheranostics for one time irradiation is highly challenging. Herein, we designed and synthesized a single-walled carbon nanohorns-based nanotheranostic agent, HA-IR808-SWNHs, by loading IR808, a photosensitizer, conjugated hyaluronic acid (HA) with an amide bond on the surface of single-walled carbon nanohorns (SWNHs) through noncovalent π-π interaction by the sonication method. The HA in HA-IR808-SWNHs improves the water dispersibility of SWNHs and endows SWNHs with targeting capabilities. Importantly, overexpressed endogenous hyaluronidase in cancer cells actively disassembles HA-IR808-SWNHs, forming small HA-IR808 fragments. The fragments exhibit a strong fluorescence signal and can be used to guide programmed photodynamic therapy for sequentially eliminating the residual living cancer cells. The current study confirms that HA-IR808-SWNHs is an endogenous enzyme-responsive nanotheranostic agent that can be employed to precisely track and ablate residual cancer cells in a spatiotemporal manner. The results strengthen the understanding of SWNH functionalization and expand its potential biomedical application, especially in cancer theranostics.

Covalent Organic Framework-Based Nanocomposite for Synergetic Photo-, Chemodynamic-, and Immunotherapies.

Cancer deaths are mainly caused by tumor metastases. However, tumor ablation therapies can only target the primary tumor but not inhibit tumor metastasis. Herein, a multifunctional covalent organic framework (COF)-based nanocomposite is designed for synergetic photo-, chemodynamic- and immunotherapies. Specifically, the synthesized COF possesses the ability to produce singlet oxygen under the 650 nm laser irradiation. After being metallized with FeCl3, p-phenylenediamine is polymerized on the surface of COF with Fe3+ as the oxidant. The obtained poly(p-phenylenediamine) can be used for photothermal therapy. Meanwhile, the overexpressed H2O2 in the tumor would be further catalyzed and decomposed into hydroxyl radicals (•OH) by the Fe3+/Fe2+ redox couple via Fenton reaction. Intriguingly, the increase of temperature caused by photothermal therapy can accelerate the production of •OH. Moreover, the tumor-associated antigen induced a robust antitumor immune response and effectively inhibited tumor metastasis in the presence of anti-PD-L1 checkpoint blockade. Such a COF-based multifunctional nanoplatform provides an efficacious treatment strategy for both the primary tumor and tumor metastasis.

A covalent organic framework as a nanocarrier for synergistic phototherapy and immunotherapy.

As traditional cancer treatment methods, photodynamic therapy (PDT) and photothermal therapy (PTT) can eliminate primary tumors, but they cannot inhibit extensive tumor metastasis and local recurrence. Herein, in order to prevent intermolecular accumulation and improve photostability, indocyanine green (ICG) is spontaneously adsorbed onto a covalent organic framework (COF) with high affinity through π-π conjugation, and then chicken ovalbumin (OVA) is coated on the surface of COF@ICG via an electrostatic interaction force. The resultant COF@ICG@OVA can ablate primary tumors under 650 nm and 808 nm laser irradiation due to its high photothermal conversion efficiency (η = 35.75%) and ability to produce reactive oxygen species (ROS). Tumor-associated antigens are also produced after combinational PTT/PDT therapy. By further combining with anti-PD-L1 checkpoint blockade therapy, it can effectively eliminate primary tumors and inhibit the metastasis of cancer cells by generating strong immune responses. Taken together, COF@ICG@OVA nanoparticles offer an efficient synergistic therapeutic modality for the treatment of tumor metastasis.

A Multifunctional Cascade Bioreactor Based on Hollow-Structured Cu2 MoS4 for Synergetic Cancer Chemo-Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy.

The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2 MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+ , Mo4+/6+ ) exhibit Fenton-like, glutathione (GSH) peroxidase-like and catalase-like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton-like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase-like CMS could react with endogenous H2 O2 to generate O2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2 O2 . The regenerated H2 O2 can devote to Fenton-like reaction for realizing GOx-catalysis-enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor-killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O2 - ) generation performance. More importantly, the PEGylated CMS@GOx-based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.

Facile synthesis of Fe-p-aminophenol nanoparticles for photothermal therapy.

Fe-p-aminophenol (Fe-PAP) nanoparticles, a newly developed photothermal agent (PTA), were successfully synthesized via a one-pot method at room temperature. The resultant product exhibited good photothermal effect with a photothermal conversion efficiency of 36%. In vitro and in vivo evaluation demonstrated that Fe-PAP was an effective PTA for photothermal therapy (PTT).

Template-free synthesis and metalation of hierarchical covalent organic framework spheres for photothermal therapy.

Uniform micron sized hierarchical COF (HCOF) spheres were fabricated by a template-free solution-based aging method at room temperature for the first time. The postsynthetic metalation of HCOF with Fe3+ makes the metalated HCOF an excellent photothermal agent (PTA) for photothermal therapy (PTT).

Yolk-Shell Structured Au Nanostar@Metal-Organic Framework for Synergistic Chemo-photothermal Therapy in the Second Near-Infrared Window.

Light-sensitive yolk-shell nanoparticles (YSNs) as remote-controlled and stimuli-responsive theranostic platforms provide an attractive method for synergistic cancer therapy. Herein, a kind of novel stimuli-responsive multifunctional YSNs has been successfully constructed by integrating star-shaped gold (Au star) nanoparticles as the second near-infrared (NIR-II) photothermal yolks and biodegradable crystalline zeolitic imidazolate framework-8 (ZIF-8) as the shells. In this platform, a chemotherapeutic drug (doxorubicin hydrochloride, DOX) was encapsulated into the cavity, which can show the behavior of controlled release due to the degradation process of ZIF-8 in the mildly acidic tumor microenvironment. Upon the 1064 nm (NIR-II biowindow) laser irradiation, gold nanostar@ZIF-8 (Au@MOF) nanoparticles exhibited outstanding synergistic anticancer effect based on their photothermal and promoted cargo release properties. Moreover, the strong NIR region absorbance endows the Au@MOF of NIR thermal imaging and photoacoustic (PA) imaging properties. This work contributes to design a stimuli-responsive "all-in-one" nanocarrier that realizes bimodal imaging diagnosis and chemo-photothermal synergistic therapy.

Integration of a highly monodisperse covalent organic framework photosensitizer with cation exchange synthesized Ag2Se nanoparticles for enhanced phototherapy.

COF-Ag2Se nanoparticles were successfully synthesized under mild conditions via a cation exchange approach using COF and CuSe as templates. The in vitro and in vivo experiments verified the excellent cancer cell killing effect and antitumor efficacy of COF-Ag2Se nanoparticles via combined photodynamic and photothermal therapy.

Monodispersed CuSe Sensitized Covalent Organic Framework Photosensitizer with an Enhanced Photodynamic and Photothermal Effect for Cancer Therapy.

Attributed to its simplicity, noninvasive features, and excellent therapeutic effect, phototherapy has recently received considerable interest. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) holds great promise in the treatment of tumors, and in order to achieve satisfactory antitumor efficacy, suitable photosensitizers are a prerequisite. In this paper, highly monodispersed covalent organic framework (COF) nanoparticles were first prepared by a mild solution-phase synthesis method at room temperature. The as-synthesized nonporphyrin containing COF nanoparticle was employed as a novel photosensitizer for PDT, which exhibited an excellent photodynamic effect under 650 or 808 nm laser irradiation. Then, CuSe nanoparticles, an ideal photothermal agent, were successfully conjugated with COF to form a dual functional photosensitizer for phototherapy. The resultant COF-CuSe platform possesses an excellent synergistic photothermal and photodynamic effect. The in vitro and in vivo experiments indicated an enhanced therapeutic effect on killing cancer cells and inhibiting the tumor growth. This work demonstrates the great potential of nonporphyrin containing COF as a photosensitizer for photodynamic cancer therapy and provides a facile and efficient approach to construct COF-based multifunctional theranostic agents for cancer diagnosis and treatment by combining COFs with other functional materials.

Boosting the antitumor efficacy over a nanoscale porphyrin-based covalent organic polymer via synergistic photodynamic and photothermal therapy.

Porphyrin-based covalent organic polymer nanoparticles were synthesized via a Schiff base reaction at room temperature. The resulting product showed a good photodynamic effect and a high photothermal conversion efficiency (34.88%). Both in vitro and in vivo experiments demonstrated the enhanced antitumor efficacy via synergistic photodynamic and photothermal therapy.

Facile Fabrication of Nanoscale Porphyrinic Covalent Organic Polymers for Combined Photodynamic and Photothermal Cancer Therapy.

Photodynamic therapy (PDT) of cancers is usually inefficient due to the relatively low level of oxygen in cancer cells; therefore, it needs to combine with other treatment strategies such as chemotherapy or photothermal therapy (PTT) to achieve the best anticancer efficacy. Although porphyrin-containing materials have been widely studied for PDT, the photothermal effect is rarely reported. Herein, nanoscale porphyrin-containing covalent organic polymers (PCOPs) were produced via a room temperature solution-based aging method. The resulting nanoparticles possess high photothermal conversion efficiency (21.7%) and excellent photodynamic effect. For the first time, the in vitro and in vivo tests indicated an enhanced antitumor efficacy for PCOP with combined PDT and PTT. This study provides an efficient approach to fabricate nanoCOP and also demonstrates the great potential of porphyrin-containing COP for biomedical applications.

Interfacially synthesized Fe-soc-MOF nanoparticles combined with ICG for photothermal/photodynamic therapy.

Recently, fabrication of nanoscale MOFs (NMOFs) has attracted great attention for biomedical applications. NMOFs not only maintain the structural diversity and physicochemical properties of bulk MOFs, but also possess suitable dimensions, making them potential nanocarriers for imaging agents and drug molecules. In this work, highly monodispersed Fe-soc-MOF nanoparticles (about 100 nm) were fabricated through the liquid-solid-solution (LSS) method. Indocyanine green (ICG) was conjugated to the surface-modified Fe-soc-MOF to construct a multifunctional theranostic platform. The Fe-soc-MOF@PEG-NH2-ICG nanoparticles (FPINs) were tested for photothermal therapy (PTT)/photodynamic therapy (PDT) both in vitro and in vivo. Due to their low toxicity, good biocompatibility and excellent photothermal/photodynamic effect, the as-synthesized FPINs could be used to inhibit and kill cancer cells efficiently under the 808 nm laser irradiation.

Self-Templated Stepwise Synthesis of Monodispersed Nanoscale Metalated Covalent Organic Polymers for In Vivo Bioimaging and Photothermal Therapy.

Size- and shape-controlled growth of nanoscale microporous organic polymers (MOPs) is a big challenge scientists are confronted with; meanwhile, rendering these materials for in vivo biomedical applications is still scarce. In this study, a monodispersed nanometalated covalent organic polymer (MCOP, M=Fe, Gd) with sizes around 120 nm was prepared by a self-templated two-step solution-phase synthesis method. The metal ions (Fe3+ , Gd3+ ) played important roles in generating a small particle size and in the functionalization of the products during the reaction with p-phenylenediamine (Pa). The resultant Fe-Pa complex was used as a template for the subsequent formation of MCOP following the Schiff base reaction with 1,3,5-triformylphloroglucinol (Tp). A high tumor suppression efficiency for this Pa-based COP is reported for the first time. This study demonstrates the potential use of MCOP as a photothermal agent for photothermal therapy (PTT) and also provides an alternative route to fabricate nano-sized MCOPs.