Dual‐Targeted Selenium Nanoparticles for Synergistic Photothermal Therapy and Chemotherapy of Tumors

A combination of chemo‐ and photothermal therapy has emerged as a promising tactic for cancer therapy. However, the intricacy of accurate delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Hence, to assure that the chemotherapeutic drug and photothermal agent are synchronously delivered to a tumor area for their synergistic effect, dual‐target (RC‐12 and PG‐6 peptides) functionalized selenium nanoparticles loaded with both doxorubicin (DOX) and indocyanine green (ICG) were designed and successfully synthesized. The as‐synthesized nanoparticles exhibited good monodispersity, size stability, and consistent spectral characteristics compared with those of ICG or DOX alone. The nanoparticles underwent self‐immolated cleavage under irradiation from a near‐IR laser and released the loaded drug owing to sufficient hyperthermia. Moreover, the internalized nanoparticles triggered the overproduction of intracellular reactive oxygen species to induce cell apoptosis. Taken together, this study provides a sequentially triggered nanosystem to achieve precise drug delivery by chemo‐photothermal combination.     

Platelet‐Facilitated Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Here, we present a platelet‐facilitated photothermal tumor therapy (PLT‐PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR‐loaded PLTs (PLT‐AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene‐knockout mouse model, we demonstrate that the administration of PLT‐AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT‐AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self‐reinforcing characteristic of PLT‐PTT in cancer therapy.     

Supramolecular Phthalocyanine Assemblies for Improved Photoacoustic Imaging and Photothermal Therapy

Phototheranostic nanoplatforms are of particular interest for cancer diagnosis and imaging‐guided therapy. Herein, we develop a supramolecular approach to fabricate a nanostructured phototheranostic agent through the direct self‐assembly of two water‐soluble phthalocyanine derivatives, PcS4 and PcN4. The nature of the molecular recognition between PcS4 and PcN4 facilitates the formation of nanostructure (PcS4‐PcN4) and consequently enables the fabrication of PcS4‐PcN4 with completely quenched fluorescence and reduced singlet oxygen generation, leading to the high photoacoustic and photothermal activity of PcS4‐PcN4. In vivo evaluations suggest that PcS4‐PcN4 could not only efficiently visualize a tumor with high contrast through whole‐body photoacoustic imaging but also enable excellent photothermal therapy for cancer.     

Tailored Synthesis of Octopus‐type Janus Nanoparticles for Synergistic Actively‐Targeted and Chemo‐Photothermal Therapy

A facile, reproducible, and scalable method was explored to construct uniform Au@poly(acrylic acid) (PAA) Janus nanoparticles (JNPs). The as‐prepared JNPs were used as templates to preferentially grow a mesoporous silica (mSiO₂) shell and Au branches separately modified with methoxy‐poly(ethylene glycol)‐thiol (PEG) to improve their stability, and lactobionic acid (LA) for tumor‐specific targeting. The obtained octopus‐type PEG‐Au‐PAA/mSiO₂‐LA Janus NPs (PEG‐OJNP‐LA) possess pH and NIR dual‐responsive release properties. Moreover, DOX‐loaded PEG‐OJNP‐LA, upon 808 nm NIR light irradiation, exhibit obviously higher toxicity at the cellular and animal levels compared with chemotherapy or photothermal therapy alone, indicating the PEG‐OJNP‐LA could be utilized as a multifunctional nanoplatform for in vitro and in vivo actively‐targeted and chemo‐photothermal cancer therapy.     

A Water‐Soluble,NIR‐Absorbing Quaterrylenediimide Chromophore for Photoacoustic Imaging and Efficient Photothermal Cancer Therapy

Precision phototheranostics, including photoacoustic imaging and photothermal therapy, requires stable photothermal agents. Developing such agents with high stability and high photothermal conversion efficiency (PTCE) remains a considerable challenge. Herein, we introduce a new photothermal agent based on water‐soluble quaterrylenediimide (QDI) that can self‐assemble into nanoparticles (QDI‐NPs) in aqueous solution. Incorporating polyethylene glycol (PEG) into the QDI core significantly enhances both physiological stability and biocompatibility of QDI‐NPs. The highly photostable QDI‐NPs offer advantages including intense absorption in the near‐infrared (NIR) and high PTCE of up to 64.7±4 %. This is higher than that of commercial indocyanine green (ICG). Their small size (ca. 10 nm) enables sustained retention in deep tumor sites and also proper clearance from the body. QDI‐NPs allow high‐resolution photoacoustic imaging and efficient 808 nm laser‐triggered photothermal therapy of cancer in vivo.     

A Water‐Soluble,NIR‐Absorbing Quaterrylenediimide Chromophore for Photoacoustic Imaging and Efficient Photothermal Cancer Therapy

Precision phototheranostics, including photoacoustic imaging and photothermal therapy, requires stable photothermal agents. Developing such agents with high stability and high photothermal conversion efficiency (PTCE) remains a considerable challenge. Herein, we introduce a new photothermal agent based on water‐soluble quaterrylenediimide (QDI) that can self‐assemble into nanoparticles (QDI‐NPs) in aqueous solution. Incorporating polyethylene glycol (PEG) into the QDI core significantly enhances both physiological stability and biocompatibility of QDI‐NPs. The highly photostable QDI‐NPs offer advantages including intense absorption in the near‐infrared (NIR) and high PTCE of up to 64.7±4 %. This is higher than that of commercial indocyanine green (ICG). Their small size (ca. 10 nm) enables sustained retention in deep tumor sites and also proper clearance from the body. QDI‐NPs allow high‐resolution photoacoustic imaging and efficient 808 nm laser‐triggered photothermal therapy of cancer in vivo.     

Ag@TiO2 Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

Melanoma is a primary reason of death from skin cancer and associated with high lethality. Photothermal therapy (PTT) has been developed into a powerful cancer treatment technique in recent years. Here, we created a low‐cost and high‐performance PTT agent, Ag@TiO₂ NPs, which possesses a high photothermal conversion efficiency of ≈65 % and strong near‐infrared (NIR) absorption about 808 nm. Ag NPs were synthesized using a two‐step method and coated with TiO₂ to obtain Ag@TiO₂ NPs by a facile sol‐gel method. Because of the oxide, Ag@TiO₂ NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO₂ NPs were tested in B16‐F10 cells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs‐treated (100 μg mL^?1) cells in vitro (both p<0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO₂ NPs (100 μg mL^?1) were injected into the tumor and irradiated with a 808 nm laser of 2 W cm^?2 for 1 minute. As a consequence, the tumor volume gradually decreased by NIR laser irradiation with only a single treatment. The results demonstrate that Ag@TiO₂ NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.     

Near‐Infrared Light and pH‐Responsive Polypyrrole@Polyacrylic acid/Fluorescent Mesoporous Silica Nanoparticles for Imaging and Chemo‐Photothermal Cancer Therapy

We have rationally designed a new theranostic agent by coating near‐infrared (NIR) light‐absorbing polypyrrole (PPY) with poly(acrylic acid) (PAA), in which PAA acts as a nanoreactor and template, followed by growing small fluorescent silica nanoparticles (fSiO₂ NPs) inside the PAA networks, resulting in the formation of polypyrrole@polyacrylic acid/fluorescent mesoporous silica (PPY@PAA/fmSiO₂) core–shell NPs. Meanwhile, DOX‐loaded PPY@PAA/fmSiO₂ NPs as pH and NIR dual‐sensitive drug delivery vehicles were employed for fluorescence imaging and chemo‐photothermal synergetic therapy in vitro and in vivo. The results demonstrate that the PPY@PAA/fmSiO₂ NPs show high in vivo tumor uptake by the enhanced permeability and retention (EPR) effect after intravenous injection as revealed by in vivo fluorescence imaging, which is very helpful for visualizing the location of the tumor. Moreover, the obtained NPs inhibit tumor growth (95.6 % of tumors were eliminated) because of the combination of chemo‐photothermal therapy, which offers a synergistically improved therapeutic outcome compared with the use of either therapy alone. Therefore, the present study provides new insights into developing NIR and pH‐stimuli responsive PPY‐based multifunctional platform for cancer theranostics.     

Synthesis of a Near‐Infrared BODIPY Dye for Bioimaging and Photothermal Therapy

The development of robust photothermal agents for near‐infrared (NIR) imaging is a great challenge. Herein, we report the design and synthesis of a new photothermal agent, based on the aza‐boron‐dipyrromethene framework (azaBDP). This compound possessed excellent photostability and high photothermal‐conversion efficiency (50 %) under NIR laser irradiation. When the photothermal properties of this compound were utilized for tumor inhibition, stable long‐term fluorescence was observed in living animals. Photothermal treatment efficiently suppressed tumor growth, as evidenced by in vitro and in vivo experiments. Furthermore, NIR emission could be detected by using an imaging system and therapeutic self‐monitoring was achieved by using NIR imaging.     

Semiconducting Polycomplex Nanoparticles for Photothermal Ferrotherapy of Cancer

This study reports the development of iron‐chelated semiconducting polycomplex nanoparticles (SPFeN) for photoacoustic (PA) imaging‐guided photothermal ferrotherapy of cancer. The hybrid polymeric nanoagent comprises a ferroptosis initiator (Fe³⁺) and an amphiphilic semiconducting polycomplex (SP_C) serving as both the photothermal nanotransducer and iron ion chelator. By virtue of poly(ethylene glycol) (PEG) grafting and its small size, SPFeN accumulates in the tumor of living mice after systemic administration, which can be monitored by PA imaging. In the acidic tumor microenvironment, SPFeN generates hydroxyl radicals, leading to ferroptosis; meanwhile, under NIR laser irradiation, it generates localized heat to not only accelerate the Fenton reaction but also implement photothermal therapy. Such a combined photothermal ferrotherapeutic effect of SPFeN leads to minimized dosage of iron compared to previous studies and effectively inhibits the tumor growth in living mice, which is not possible for the controls.     

Simultaneous Application of Photothermal Therapy and an Anti‐inflammatory Prodrug using Pyrene–Aspirin‐Loaded Gold Nanorod Graphitic Nanocapsules

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT‐induced inflammatory response. 1‐Pyrene methanol was utilize to synthesize the anti‐inflammatory prodrug pyrene–aspirin (P‐aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)‐encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π–π interactions. Such AuNR@G‐P‐aspirin complexes were used for near‐infrared laser‐triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT‐induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.     

Spindle‐Like Polypyrrole Hollow Nanocapsules as Multifunctional Platforms for Highly Effective Chemo–Photothermal Combination Therapy of Cancer Cells in Vivo

The monodispersed spindle‐like polypyrrole hollow nanocapsules (PPy HNCs) as the multifunctional platforms for combining chemotherapy with photothermal therapy for cancer cells are reported. Whereas the hollow cavity of nanocapsules can be used to load the anticancer drug (i.e., doxorubicin) for chemotherapy, the PPy shells can convert NIR light into heat for photothermal therapy. The release of the drug from the spindle‐like PPy HNCs is pH‐sensitive and near‐infrared (NIR) light‐enhanced. More importantly, the spindle‐like PPy HNCs can penetrate cells more rapidly and efficiently in comparison with the spherical PPy HNCs. Both in vitro and in vivo experiments demonstrated that the combination of DOX‐loaded spindle‐like PPy HNCs and NIR light provide a highly effective and feasible chemo‐photothermal therapy cancer method with a synergistic effect. Owing to their high photothermal conversion efficiency, large hollow cavity, and good biocompatibility, the spindle‐like PPy HNCs could be used as a promising new cancer drug‐nanocarrier and photothermal agent for localized tumorous chemo‐photothermal therapy.     

Macrotheranostic Probe with Disease‐Activated Near‐Infrared Fluorescence,Photoacoustic, and Photothermal Signals for Imaging‐Guided Therapy

Theranostics provides opportunities for precision cancer therapy. However, theranostic probes that simultaneously turn on their diagnostic signal and pharmacological action only in respond to a targeted biomarker have been less exploited. We herein report the synthesis of a macrotheranostic probe that specifically activates its near‐infrared fluorescence (NIRF), photoacoustic (PA), and photothermal signals in the presence of a cancer‐overexpressed enzyme for imaging‐guided cancer therapy. Superior to the small‐molecule counterpart probe, the macrotheranostic probe has ideal biodistribution and renal clearance, permitting passive targeting of tumors, in situ activation of multimodal signals, and effective photothermal ablation. Our study thus provides a macromolecular approach towards activatable multimodal phototheranostics.     

Thermohydrogel Containing Melanin for Photothermal Cancer Therapy

Melanin is an effective absorber of light and can extend to near infrared (NIR) regions. In this study, a natural melanin is presented as a photothermal therapeutic agent (PTA) because it provides a good photothermal conversion efficiency, shows biodegradability, and does not induce long‐term toxicity during retention in vivo. Poloxamer solution containing melanin (Pol–Mel) does not show any precipitation and shows sol–gel transition at body temperature. After irradiation from 808 nm NIR laser at 1.5 W cm⁻² for 3 min, the photothermal conversion efficiency of Pol–Mel is enough to kill cancer cells in vitro and in vivo. The tumor growth of mice bearing CT26 tumors treated with Pol–Mel injection and laser irradiation is suppressed completely without recurrence postirradiation. All these results indicate that Pol–Mel can become an attractive PTA for photothermal cancer therapy.

     

Macrotheranostic Probe with Disease‐Activated Near‐Infrared Fluorescence,Photoacoustic, and Photothermal Signals for Imaging‐Guided Therapy

Theranostics provides opportunities for precision cancer therapy. However, theranostic probes that simultaneously turn on their diagnostic signal and pharmacological action only in respond to a targeted biomarker have been less exploited. We herein report the synthesis of a macrotheranostic probe that specifically activates its near‐infrared fluorescence (NIRF), photoacoustic (PA), and photothermal signals in the presence of a cancer‐overexpressed enzyme for imaging‐guided cancer therapy. Superior to the small‐molecule counterpart probe, the macrotheranostic probe has ideal biodistribution and renal clearance, permitting passive targeting of tumors, in situ activation of multimodal signals, and effective photothermal ablation. Our study thus provides a macromolecular approach towards activatable multimodal phototheranostics.     

Multifunctional Uniform Core–Shell Fe3O4@mSiO2 Mesoporous Nanoparticles for Bimodal Imaging and Photothermal Therapy

Multimodal imaging and simultaneous therapy is highly desirable because it can provide complementary information from each imaging modality for accurate diagnosis and, at the same time, afford an imaging‐guided focused tumor therapy. In this study, indocyanine green (ICG), a near‐infrared (NIR) imaging agent and perfect NIR light absorber for laser‐mediated photothermal therapy, was successfully incorporated into superparamagnetic Fe₃O₄@mSiO₂ core–shell nanoparticles to combine the merit of NIR/magnetic resonance (MR) bimodal imaging properties with NIR photothermal therapy. The resultant nanoparticles were homogenously coated with poly(allylamine hydrochloride) (PAH) to make the surface of the composite nanoparticles positively charged, which would enhance cellular uptake driven by electrostatic interactions between the positive surface of the nanoparticles and the negative surface of the cancer cell. A high biocompatibility of the achieved nanoparticles was demonstrated by using a cell cytotoxicity assay. Moreover, confocal laser scanning microscopy (CLSM) observations indicated excellent NIR fluorescent imaging properties of the ICG‐loaded nanoparticles. The relatively high r₂ value (171.6 mM ^?1 s^?1) of the nanoparticles implies its excellent capability as a contrast agent for MRI. More importantly, the ICG‐loaded nanoparticles showed perfect NIR photothermal therapy properties, thus indicating their potential for simultaneous cancer diagnosis as highly effective NIR/MR bimodal imaging probes and for NIR photothermal therapy of cancerous cells.     

Deep‐Level Defect Enhanced Photothermal Performance of Bismuth Sulfide–Gold Heterojunction Nanorods for Photothermal Therapy of Cancer Guided by Computed Tomography Imaging

Bismuth sulfide (Bi₂S₃) nanomaterials are emerging as a promising theranostic platform for computed tomography imaging and photothermal therapy of cancer. Herein, the photothermal properties of Bi₂S₃ nanorods (NRs) were unveiled to intensely correlate to their intrinsic deep‐level defects (DLDs) that potentially could work as electron–hole nonradiative recombination centers to promote phonon production, ultimately leading to photothermal performance. Bi₂S₃‐Au heterojunction NRs were designed to hold more significant DLD properties, exhibiting more potent photothermal performance than Bi₂S₃ NRs. Under 808 nm laser irradiation, Bi₂S₃‐Au NRs could trigger higher cellular heat shock protein 70 expression and more apoptotic cells than Bi₂S₃ NRs, and caused severe cell death and tumor growth inhibition, showing great potential for photothermal therapy of cancer guided by computed tomography imaging.     

Dual‐Mode Antibacterial Conjugated Polymer Nanoparticles for Photothermal and Photodynamic Therapy

In this work, dual‐mode antibacterial conjugated polymer nanoparticles (DMCPNs) combined with photothermal therapy (PTT) and photodynamic therapy (PDT) are designed and explored for efficient killing of ampicillin‐resistant Escherichia coli (Amp^r E. coli). The DMCPNs are self‐assembled into nanoparticles with a size of 50.4 ± 0.6 nm by co‐precipitation method using the photothermal agent poly(diketopyrrolopyrrole‐thienothiophene) (PDPPTT) and the photosensitizer poly[2‐methoxy‐5‐((2‐ethylhexyl)oxy)‐p‐phenylenevinylene] (MEH‐PPV) in the presence of poly(styrene‐co‐maleic anhydride) which makes nanoparticles disperse well in water via hydrophobic interactions. Thus, DMCPNs simultaneously possess photothermal effect and the ability of sensitizing oxygen in the surrounding to generate reactive oxygen species upon the illumination of light, which could easily damage resistant bacteria. Under combined irradiation of near‐infrared light (550 mW cm^?2, 5 min) and white light (65 mW cm^?2, 5 min), DMCPNs with a concentration of 9.6 × 10^?4 µm could reach a 93% inhibition rate against Amp^r E. coli, which is higher than the efficiency treated by PTT or PDT alone. The dual‐mode nanoparticles provide potential for treating pathogenic infections induced by resistant microorganisms in clinic.     

Copper Sulfide Nanoparticles with Phospholipid‐PEG Coating for In Vivo Near‐Infrared Photothermal Cancer Therapy

In this work, small sizes of hydrophobic copper sulfide nanoparticles (CuS NPs, ～3.8 nm in diameter) have been successfully prepared from the reaction of copper chloride with sodium diethyldithiocarbamate (SDEDTC) inside a heated oleylamine solution. These CuS NPs displayed strong absorption in the 700–1100 nm near‐infrared (NIR) region. By coating CuS NPs with DSPE‐PEG2000 on the surface, the as‐synthesized CuS@DSPE‐PEG NPs exhibited good water solubility, significant stability and biocompatibility, as well as excellent photothermal conversion effects upon exposure to an 808 nm laser. After intravenous administration to mice, the CuS@DSPE‐PEG NPs were found to passively target to the tumor site, and tumor tissues could be ablated efficiency under laser irradiation. In addition, CuS@DSPE‐PEG NPs do not show significant toxicity by histological and blood chemistry analysis, and can be effectively excreted via metabolism. Our results indicated that CuS@DSPE‐PEG NPs can act as an ideal photothermal agent for cancer photothermal therapy.     

Black Pigment Gallstone Inspired Platinum‐Chelated Bilirubin Nanoparticles for Combined Photoacoustic Imaging and Photothermal Therapy of Cancers

Bilirubin (BR), a bile pigment that exerts potent antioxidant and anti‐inflammatory effects, is also a major constituent of black pigment gallstones found in bile ducts under certain pathological conditions. Inspired by the intrinsic metal‐chelating power of BR found in gallstones, herein we report a cisplatin‐chelated BR‐based nanoparticle (cisPt@BRNP) for use as a new photonic nanomedicine for combined photoacoustic imaging and photothermal therapy of cancers. The cisPt@BRNPs were prepared by simply mixing cisplatin with BRNPs, yielding ca. 150‐nm‐size NPs. Upon near‐IR laser irradiation at 808 nm, cisPt@BRNPs generated considerable heat and induced clear death of cancer cells in vitro. Following intravenous injection into human colon cancer‐bearing mice, cisPt@BRNPs allowed effective tumor visualization by photoacoustic imaging and remarkable antitumor efficacy by photothermal therapy, suggesting their potential for use as a new photonic nanomedicine for cancer therapy.