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Integrating the ultralong excitation wavelength, high extinction coefficient, and prominent photothermal conversion ability into a single photothermal agent is an appealing yet significantly challenging task. Herein, a precise dual‐acceptor engineering strategy is exploited for this attempt based on donor‐acceptor (D‐A) type semiconductor polymers by subtly regulating the molar proportions of the two employed electron acceptor moieties featuring different electronic affinity and π‐conjugation degrees, and making full use of the active intramolecular motion‐induced photothermal effect. The optimal polymer SP4 synchronously shows desirable second near‐infrared (NIR‐II) absorption, an extremely high extinction coefficient, and satisfactory photothermal conversion behavior. Consequently, the unprecedented performance of SP4 NPs on 1064 nm laser‐excited photoacoustic imaging (PAI)‐guided photothermal therapy (PTT) is demonstrated by the precise tumor diagnosis and complete tumor elimination. [ABSTRACT FROM AUTHOR]

Synergistic photothermal immunotherapy has captured great attention owing to the mutually strengthening therapeutic outcomes towards both original tumors and abscopal tumors. Herein, a versatile theranostic agent displaying aggregation‐induced emission, namely TPA‐BT‐DPTQ, was designed and prepared based on benzo[c]thiophene unit as a building block; it can be used for simultaneous fluorescence imaging (FLI) in the second near‐infrared (NIR‐II) window, photoacoustic imaging (PAI), photothermal imaging (PTI), and thermal eradication of tumors. Further experiments validate that photothermal therapy (PTT) mediated by TPA‐BT‐DPTQ nanoparticles not only destroys the primary tumor but also enhances immunogenicity for further suppressing the growth of tumors at distant sites. Furthermore, PTT combining a programmed death‐ligand 1 (PD‐L1) antibody prevents the metastasis and recurrence of cancer by potentiating the effect of immunotherapy. [ABSTRACT FROM AUTHOR]

Supramolecular approaches have opened up vast possibilities to construct versatile materials, especially those with stimuli‐responsiveness and integrated functionalities of multi‐modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY‐Py⊂CP5@AuNR is constructed via facile host–guest interactions, where TTPY‐Py is a photosensitizer with aggregation‐induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)‐modified Au nanorods. TTPY‐Py⊂CP5@AuNR integrates the respective advantages of TTPY‐Py and CP5@AuNR such as the high performance of reactive oxygen species generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY‐Py for further theranostic applications. Significantly, in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potential for FLI‐PAI imaging‐guided synergistic PDT‐PTT therapy. Moreover, TTPY‐Py can be released upon activation by the acidic environment of lysosomes and then specifically light up mitochondria. This study demonstrates a new strategy for the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies. [ABSTRACT FROM AUTHOR]

Graphical abstract AuNCs-HA exhibited PA imaging guided combined radiotherapy, PDT and PTT trimodalites, leading to effectively synergistic anticancer efficacy. Abstract In this work, we developed a novel multifunctional nanoplatform based on hyaluronic acid modified Au nanocages (AuNCs-HA). The rational design of AuNCs-HA renders the nanoplatform three functionalities: (1) AuNCs-HA with excellent LSPR peak in the NIR region act as contrast agent for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT); (2) the nanoplatform with high-energy rays (X-ray) absorption and auger electrons generation acts as a radiosensitizer for radiotherapy; (3) good photocatalytic property and large surface area make AuNCs-HA a photosensitive agent for photodynamic therapy (PDT). In vivo results demonstrated that AuNCs-HA presented excellent PA imaging performance after intravenous injection, which provided contour, size, and location information of the tumor. Moreover, because AuNCs-HA could combine radiotherapy and phototherapy together, the tumors treated with AuNCs-HA showed complete growth inhibition, comparing to that with each therapy alone. Taken together, our present study demonstrates that AuNCs-HA is of great potential as a multifunctional nanoplatform for PA imaging-guided radio- and photo-therapy of tumor. Statement of Significance In this study, a commendable theranostic nanoplatform based on hyaluronic acid modified AuNCs (AuNCs-HA) was developed. In our approach, the dilute solution of Gold(III) chloride is slowly dripped into Ag nanocubes solution, then the Au nanocages were obtained by redox reaction, and followed by HA modification. We explored them, simultaneously, as radiosensitizers for RT, photosensitizers for PDT, and therapeutic agents for PTT. Compared to that of each therapies alone, the combination of radio-therapy and photo-therapy results in a considerably improved tumor eliminating effect and efficiently inhibited tumor growth. In addition, AuNCs-HA exhibited remarkably strong PA signals for precise identification of the location, size, and boundary of the tumor, thereby facilitating imaging-guided therapy. In brief, our design of AuNCs-HA represents a general and versatile strategy for building up cancer-targeted nanotheranostics with desired synergistic imaging and therapy functionalities. [ABSTRACT FROM AUTHOR]