In this work, a nanoscale reduced graphene oxide-iron oxide nanoparticle (RGO-IONP) complex is noncovalently functionalized with polyethylene glycol (PEG), obtaining a RGO-IONP-PEG nanocomposite with excellent physiological stability, strong NIR optical absorbance, and superparamagnetic properties. Using this theranostic nanoprobe, in-vivo triple modal fluorescence, photoacoustic, and magnetic resonance imaging are carried out, uncovering high passive tumor targeting, which is further used for effective photothermal ablation of tumors in mice.

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Enhanced near-field at noble metal nanoparticle surfaces due to localized surface plasmon resonance (LSPR) has been researched in fields ranging from biomedical to photoelectrical applications. However, it is rarely explored on nonmetallic nanomaterials discovered in recent years, which can also support LSPR by doping-induced free charge carriers, let alone the investigation of an intricate system involving both. Here we construct a dual plasmonic hybrid nanosystem Au-Cu9S5 with well controlled interfaces to study the coupling effect of LSPR originating from the collective electron and hole oscillations. Cu9S5 LSPR is enhanced by 50% in the presence of Au, and the simulation results confirm the coupling effect and the enhanced local field as well as the optical power absorption on Cu9S5 surface. This enhanced optical absorption cross section, high photothermal transduction efficiency (37%), large light penetration depth at 1064 nm, excellent X-ray attenuation ability, and low cytotoxicity enable Au-Cu9S5 hybrids for robust photothermal therapy in the second near-infrared (NIR) window with low nanomaterial dose and laser flux, making them potential theranostic nanomaterials with X-ray CT imaging capability. This study will benefit future design and optimization of photoabsorbers and photothermal nanoheaters utilizing surface plasmon resonance enhancement phenomena for a broad range of applications.

Jack of all trades: A multifunctional nanoparticle (MFNP) integrates an upconversion nanoparticle (see picture, green), a layer of iron oxide nanoparticles (black), and a gold shell (red). The system can be used for in vitro targeted upconversion luminescence, magnetic resonance, and light scattering multimodal imaging of cells. The near‐infrared optical absorption of MFNPs also enables photothermal destruction of cancer cells.

Multifunctional nanoplatforms that are safe and have multiple therapeutic functions together with imaging capabilities are highly demanded in the development of new cancer theranostic approaches. A number of near-infrared (NIR)-absorbing inorganic nanomaterials, although having shown great promise not only to photothermally ablate tumors but also to enhance the efficacy of other types of therapies, are not biodegradable and would be retained in the body for a long time. Herein, we develop a multifunctional nanocomposite by coating magnetic iron oxide nanoclusters with a near-infrared light-absorbing polymer polypyrrole (PPy), obtaining Fe3O4@PPy core-shell nanoparticles, which after functionalization with polyethylene glycol could be used for imaging-guided, remotely controlled cancer combination therapy. In this system, the Fe3O4 core, which could be gradually decomposed in physiological environments, is useful for magnetically controlled drug delivery as well as a magnetic resonance imaging contrast. The PPy shell, as an organic polymer, is able to load therapeutic molecules with aromatic structures and also exhibits a strong photothermal effect, which can be used to enhance the chemotherapeutic efficacy, showing an outstanding in vivo synergistic antitumor effect. Our work encourages further exploration of light-absorbing polymer-based nanocomposites for cancer combination therapy under remote physical controls.

Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO2) nanoparticles toward endogenous hydrogen peroxide (H2O2) within the tumor microenvironment to generate O2, multifunctional chlorine e6 (Ce6) loaded MnO2 nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO2‐PEG) are formulated to achieve enhanced tumor‐specific PDT. In vitro studies under an oxygen‐deficient atmosphere uncover that Ce6@MnO2‐PEG nanoparticles could effectively enhance the efficacy of light‐induced PDT due to the increased intracellular O2 level benefited from the reaction between MnO2 and H2O2, the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO2‐PEG nanoparticles upon intravenous injection as revealed by T1‐weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO2‐PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.

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Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue‐penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen‐deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging‐guided enhanced SDT against cancer. As‐made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX‐PEG nanoparticles exhibit highly efficient US‐triggered production of 1O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen‐deficient structure of MnWOX serves as an electron trap site to prevent electron–hole recombination. The glutathione depletion capability of MnWOX‐PEG can also further favor SDT‐triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX‐PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX‐PEG can be metabolized by the mouse body without any long‐term toxicity. Herein, a new type of sono‐sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.