Long-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment.

The role of tumor-resident intracellular microbiota (TRIM) in carcinogenesis has sparked enormous interest. Nevertheless, the impact of TRIM-targeted antibacteria on tumor inhibition and immune regulation in the tumor microenvironment (TME) remains unexplored. Herein, we report long-term relapse-free survival by coordinating antibacteria with antitumor treatment, addressing the aggravated immunosuppression and tumor overgrowth induced by TRIM using breast and prostate cancer models. Combining Ag+ release with a Fenton-like reaction and photothermal conversion, simultaneous bacteria killing and multimodal antitumor therapy are enabled by a single agent. Free of immune-stimulating drugs, the agent restores antitumor immune surveillance and activates immunological responses. Secondary inoculation and distal tumor analysis confirm lasting immunological memory and systemic immune responses. A relapse-free survival of >700 days is achieved. This work unravels the crucial role of TRIM-targeted antibacteria in tumor inhibition and unlocks an unconventional route for immune regulation in TME and a complete cure for cancer.

Au@MnSe2 Core-Shell Nanoagent Enabling Immediate Generation of Hydroxyl Radicals and Simultaneous Glutathione Deletion Free of Pre-Reaction for Chemodynamic-Photothermo-Photocatalytic Therapy with Significant Immune Response.

As a typical tumor microenvironment-responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (• OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: • OH generated from endogenous H2 O2 is usually insufficient; the CDT effect is strongly dependent on the pre-reaction with glutathione. Addressing the challenges, Au@MnSe2 core-shell nanoagent for synergetic chemodynamic-photothermo-photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione-depleting agents, Mn2+ in MnSe2 allows immediate generation of • OH, independent of pre-reaction. Meanwhile, Mn3+ consumes glutathione by its conversion to Mn2+ . The Au-MnSe2 combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced • OH generation from endogenous H2 O2 and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death-1 and proinflammatory cytokines increase to 4-7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5-folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly-integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high-performance theranostic nanoagents.

Photothermal conversion-coordinated Fenton-like and photocatalytic reactions of Cu2-xSe-Au Janus nanoparticles for tri-combination antitumor therapy.

In vivo chemical reactions activated by the tumor microenvironment (TME) are particularly promising for antitumor treatments. Herein, employing Cu2-xSe-Au Janus nanoparticles (NPs), photothermal conversion-coordinated Fenton-like and photocatalytic reactions are demonstrated in vitro/vivo. The amorphous form of Cu2-xSe and the catalytic effect of Au benefit the OH generation, and the photo-induced electron‒hole separation of the Janus NPs produces additional OH. The plasmonic electrons of Au facilitate the conversion from Cu2+ to Cu+. Both Cu2-xSe and Au contributes to the efficient photothermal conversion, further promoting the reactions. As a result, the H2O2 utilization rate is largely increased, and remarkable generation of reactive oxygen species is achieved by cell endogenous H2O2in vitro/vivo. A competent tumor inhibition effect is afforded, with high-contrast multimodal imaging. This work opens up the route synergistically integrating photothermal therapy with chemodynamic therapy and photocatalytic therapy into tri-combination antitumor therapy, simply by heterojunction of semiconductor and noble metal.

Carbon dots-fed Shewanella oneidensis MR-1 for bioelectricity enhancement.

Bioelectricity generation, by Shewanella oneidensis (S. oneidensis) MR-1, has become particularly alluring, thanks to its extraordinary prospects for energy production, pollution treatment, and biosynthesis. Attempts to improve its technological output by modification of S. oneidensis MR-1 remains complicated, expensive and inefficient. Herein, we report on the augmentation of S. oneidensis MR-1 with carbon dots (CDs). The CDs-fed cells show accelerated extracellular electron transfer and metabolic rate, with increased intracellular charge, higher adenosine triphosphate level, quicker substrate consumption and more abundant extracellular secretion. Meanwhile, the CDs promote cellular adhesion, electronegativity, and biofilm formation. In bioelectrical systems the CDs-fed cells increase the maximum current value, 7.34 fold, and power output, 6.46 fold. The enhancement efficacy is found to be strongly dependent on the surface charge of the CDs. This work demonstrates a simple, cost-effective and efficient route to improve bioelectricity generation of S. oneidensis MR-1, holding promise in all relevant technologies.

Porous Ultrathin NiSe Nanosheet Networks on Nickel Foam for High-Performance Hybrid Supercapacitors.

Transition metal selenides (TMSs) with excellent electrochemical activity and high intrinsic electrical conductivity have attracted considerable attention owing to their potential use in energy storage devices. However, the low energy densities of the reported TMSs, which originate from the small active surface area and poor electrolyte ion mobility, substantially restrict their application potential. In this work, porous ultrathin nickel selenide nanosheet networks (NiSe NNs) on nickel foam are fabricated by using a novel, facile method, that is, selenylation/pickling of the pre-formed manganese-doped α-Ni(OH)2 . Removal of Mn resulted in NNs with a highly porous structure. The 3D framework of the NNs and the inherent nature of the NiSe affords high ion mobility, abundant accessible activated sites, vigorous electrochemical activity, and low resistance. One of the highest specific capacities of TMSs ever reported, that is, 443 mA h g-1 (807 µAh cm-2 ) at 3.0 A g-1 , is achieved with the NNs as electrodes. The assembled NiSe NNs//porous carbon hybrid supercapacitor delivers a high energy density of 66.6 Wh kg-1 at a power density of 425 W kg-1 , with excellent cycling stability. This work provides a new strategy for the production of novel electrode materials that can be applied in high-performance hybrid supercapacitors, and a fresh pathway towards commercial applications of hybrid supercapacitors based on TMS electrodes.

Diameter-optimized high-order waveguide nanorods for fluorescence enhancement applied in ultrasensitive bioassays.

Development of fluorescence enhancement (FE) platforms based on ZnO nanorods (NRs) has sparked considerable interest, thanks to their well-demonstrated potential in chemical and biological detection. Among the multiple factors determining the FE performance, high-order waveguide modes are specifically promising in boosting the sensitivity and realizing selective detection. However, quantitative experimental studies on the influence of the NR diameter, substrate, and surrounding medium, on the waveguide-based FE properties remain lacking. In this work, we have designed and fabricated a FE platform based on patterned and well-defined arrays of vertical, hexagonal prism ZnO NRs with six distinct diameters. Both direct experimental evidence and theoretical simulations demonstrate that high-order waveguide modes play a crucial role in FE, and are strongly dependent on the NR diameter, substrate, and surrounding medium. Using the optimized FE platform, a significant limit of detection (LOD) of 10-16 mol L-1 for Rhodamine-6G probe detection is achieved. Especially, a LOD as low as 10-14 g mL-1 is demonstrated for a prototype biomarker of carcinoembryonic antigen, which is improved by one order compared with the best LOD ever reported using fluorescence-based detection. This work provides an efficient path to design waveguiding NRs-based biochips for ultrasensitive and highly-selective biosensing.

Dual-Stimuli Responsive Bismuth Nanoraspberries for Multimodal Imaging and Combined Cancer Therapy.

Development of stimuli-responsive theranostics is of great importance for precise cancer diagnosis and treatment. Herein, bovine serum albumin (BSA) modified bismuth nanoraspberries (Bi-BSA NRs) are developed as cancer theranostic agents for multimodal imaging and chemo-photothermal combination therapy. The Bi-BSA NRs are synthesized in aqueous phase via a facile reduction method using Bi2O3 nanospheres as the sacrificial template. The morphology, biocompatibility, photothermal effect, drug loading/releasing abilities, chemotherapy effect, synergistic chemo-photothermal therapy efficacy, and multimodal imaging capacities of Bi-BSA NRs have been investigated. The results show that the NRs possess multiple unique features including (i) raspberry-like morphology with high specific surface area (∼52.24 m2·g-1) and large cavity (total pore volume ∼0.30 cm3·g-1), promising high drug loading capacity (∼69 wt %); (ii) dual-stimuli responsive drug release, triggered by acidic pH and NIR laser irradiation; (iii) infrared thermal (IRT), photoacoustic (PA) and X-ray computed tomography (CT) trimodality imaging with the CT contrast enhanced efficiency as high as ∼66.7 HU·mL·mg-1; (iv) 100% tumor elimination through the combination chemo-photothermal therapy. Our work highlights the great potentials of Bi-BSA NRs as a versatile theranostics for multimodal imaging and combination therapy.

Phase-Transition Induced Conversion into a Photothermal Material: Quasi-Metallic WO2.9 Nanorods for Solar Water Evaporation and Anticancer Photothermal Therapy.

Phase transition from WO3 to sub-stoichiometric WO2.9 by a facile method has varied the typical semiconductor to be quasi-metallic with a narrowed band gap and a shifted Femi energy to the conduction band, while maintaining a high crystallinity. The resultant WO2.9 nanorods possess a high total absorption capacity (ca. 90.6 %) over the whole solar spectrum as well as significant photothermal conversion capability, affording a conversion efficiency as high as around 86.9 % and a water evaporation efficiency of about 81 % upon solar light irradiation. Meanwhile, the promising potential of the nanorods for anticancer photothermal therapy have been also demonstrated, with a high photothermal conversion efficiency (ca. 44.9 %) upon single wavelength near-infrared irradiation and a high tumor inhibition rate (ca. 98.5 %). This study may have opened up a feasible route to produce high-performance photothermal materials from well-developed oxides.

Xanthine Quartets on Au(111).

The quartet of xanthine (X), a purine base ubiquitously distributed in most human body tissues and fluids, has been for the first time fabricated and visualized, as the first alternative purine quartet besides the known guanine (G)-quartet. The X-quartet network is demonstrated to be the most stable phase on Au(111). Unlike guanine, the fabrication of the X-quartets is not dependent on the presence of metal atoms, which makes it the first metal-free purine quartet. The X-quartet holds great promise to potentially construct artificial new DNA quadruplexes for genetic regulation and antitumor therapy. Moreover, both the X-quartet itself and the quartet networks favor homochirality, suggesting homochiral xanthine oligomers and the networks may have been formed as the precursors of the pristine oligonucleotides on primitive Earth.

Multifunctional Bi@PPy-PEG Core-Shell Nanohybrids for Dual-Modal Imaging and Photothermal Therapy.

High-performance theranostic nanoagents, which integrate multimodal imaging and photothermal therapy for clinical anticancer treatment, are highly desired. Herein, we report the synthesis and bioapplication of a multifunctional theranostic nanoagent based on polyethylene glycol (PEG)-modified polypyrrole (PPy)-coated bismuth (Bi) nanohybrids (referred to as Bi@PPy-PEG NHs) for X-ray computed tomography/photoacoustic (CT/PA) dual-modal imaging and photothermal therapy (PTT). The obtained Bi@PPy-PEG NHs have a distinct core-shell structure with the metallic Bi nanoparticle as the inner core and the PPy-PEG layer as the shell. The Bi@PPy-PEG NHs show excellent physiological stability and compatibility, without noticeable cytotoxicity. Importantly, the NHs exhibit strong NIR absorbance and remarkable photothermal conversion capability and conversion stability, with the photothermal conversion efficiency as high as ∼46.3%. Thanks to the strong PTT effect, highly effective photothermal ablation on cancer cells has been achieved both in vitro and in vivo. Furthermore, a high-contrast in vitro and in vivo CT/PA dual-modal imaging has been realized, showing great potential to provide comprehensive diagnosis information for antitumor treatment. In particular, the CT enhancement efficiency of the NHs is of ∼14.4 HU mM-1, which is ∼3.7-fold that of clinically used iohexol. Therefore, our work highlights the potential of using such core-shell Bi@PPy-PEG NHs as a versatile theranostic nanoplatform for cancer imaging and therapy.

Design and mechanism of core-shell TiO2 nanoparticles as a high-performance photothermal agent.

Photothermal agents (PTAs) with high biocompatibility and therapeutic efficacy have become particularly fascinating, however, knowledge of their photothermal performance is rather limited. Herein, rationally designed core-shell TiO2 nanoparticles have been fabricated using a mild hydrogenation method, where NaBH4 was used as the H2 source. The resultant TiO2 possesses strong optical absorption in the NIR region and remarkable photothermal conversion capability and stability, leading to a high inhibition rate on cancer cells. In particular, its photothermal conversion efficiency is as high as 55.2%, which is 204% that of the fully hydrogenated amorphous TiO2. More importantly, the underlying mechanism is proposed. It is revealed that while the oxygen vacancies induced by the hydrogenation can introduce defect levels in the band gap and enhance the optical absorption, the superfluous oxygen vacancies and defects reduce the photothermal conversion capability and thermal conductivity to a large extent. Controlling the hydrogenation degree and maintaining a certain extent of crystallization are, therefore, crucial to the photothermal properties. This new understanding of the photothermal conversion mechanism may have provided a fresh route to design and optimize PTAs and inspire considerable interest to turn a large variety of semiconductor metal oxides into competent PTAs by appropriate hydrogenation.

Dual-delivery of FGF-2/CTGF from Silk Fibroin/PLCL-PEO Coaxial Fibers Enhances MSC Proliferation and Fibrogenesis.

The success of mesenchymal stem cell transplantation is highly dependent on their survival and controlled fate regulation. This study demonstrates that dual-delivery of connective tissue growth factor (CTGF) and fibroblast growth factor 2 (FGF-2) from a core-shell fiber of Silk Fibroin/poly(L-lactic acid-co-ε-caprolactone)-polyethylene oxide (SF/PLCL-PEO) enhanced fibrogenic lineage differentiation of MSCs. The core-shell structure was confirmed by transmission electron microscopy (TEM), fluorescence microscopy and attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy. A sequential release of FGF-2 and CTGF was successfully achieved in this manner. FGF-2 plays an important role in stem cell proliferation and, meanwhile when accompanied with CTGF, has a slightly additive effect on fibrogenic differentiation of MSCs, whereas CTGF promotes fibrogenesis and alleviates osteogenesis, chondrogenesis and adipogenesis.

Biocompatible PEGylated bismuth nanocrystals: "All-in-one" theranostic agent with triple-modal imaging and efficient in vivo photothermal ablation of tumors.

Biocompatible single-component theranostic agents integrating multimodal imaging and therapeutic functions (namely, "all-in one" agents) are highly desired for clinical cancer treatments. Herein, PEGylated pure metallic bismuth nanocrystals (Bi-PEG NCs) have been developed to be a competent theranostic agent for in vivo high-performance multimodal bio-imaging and photothermal ablation of tumors. The resultant Bi-PEG NCs show excellent physiological stability, biocompatibility, prolonged blood circulation half-life and preferential tumor accumulation. Thanking to the strong near-infrared (NIR) absorbance as well as the high photothermal conversion efficiency and conversion stability, highly effective in vivo photothermal ablation on tumors has been realized upon NIR irradiation, without noticeable toxicity. Impressively, the Bi-PEG NCs show ultrahigh X-ray computed topography (CT) enhancement efficiency (∼60.3 HU mL mg-1), overwhelming all CT contrast agents reported so far. Combining the strong CT contrast ability and photoacoustic/photothermal effect, high-contrast CT, photoacoustic (PA) and infrared thermal (IRT) triple-modal imaging have been demonstrated both in vitro and in vivo. This work highlights the potentials of such NCs as a powerful "all-in-one" theranostic nanoplatform for bioimaging and antitumor therapy, and may have provided a rather promising candidate for clinically-applied antitumor treatments based on single-component agents.

Light responsive hybrid nanofibres for on-demand therapeutic drug and cell delivery.

Smart materials for on-demand delivery of therapeutically active agents are challenging in pharmaceutical and biomaterials science. In the present study, we report hybrid nanofibres capable of being reversibly controlled to pulsatile deliver both therapeutic drugs and cells on-demand of near-infrared (NIR) light. The nanofibres, fabricated by co-electrospinning of poly (N-isopropylacrylamide), silica-coated gold nanorods and polyhedral oligomeric silsesquinoxanes have, for the first time, demonstrated rapid, reversible large-volume changes of 83% on-demand with NIR stimulation, with retained nanofibrous morphology. Combining with the extracellular matrix-mimicking fibrillary properties, the nanofibres achieved accelerated release of model drug or cells on demand with NIR triggering. The release of the model drug doxorubicin demonstrated normal anti-cancer efficacy by reducing the viability of human cervical cancer HeLa cells by 97% in 48 h. In parallel, the fibres allowed model cell NIH3T3 fibroblast entrapment, adhesion, proliferation, differentiation and, upon NIR irradiation, cell release with undisturbed cellular function. Copyright © 2016 John Wiley & Sons, Ltd.

Multimodal Imaging-Guided Antitumor Photothermal Therapy and Drug Delivery Using Bismuth Selenide Spherical Sponge.

Elaborately designed biocompatible nanoplatforms simultaneously having diverse therapeutic and imaging functions are highly desired for biomedical applications. Herein, a Bi2Se3 nanoagent with a special morphology as a nanoscale spherical sponge (NSS) has been fabricated and investigated in vitro and in vivo. The highly porous NSS exhibits strong, steady, and broad-band absorbance in the near-infrared range as well as high efficiency and stability of photothermal conversion, resulting in high antitumor efficacy for photothermal therapy (PTT). Together with a high X-ray attenuation coefficient (218% that of the clinically used iopromide), the NSS shows excellent performance on triple-modal high-contrast imaging, including X-ray-computed tomography, multispectral optoacoustic tomography, and infrared thermal imaging. Furthermore, the high surface area and porous structure impart the NSS a competent drug loading capability as high as 600% of that on Bi2Se3 nanoplates, showing a bimodal pH/photothermal sensitive drug release and pronounced synergetic effects of thermo-chemotherapy with a tumor inhibition ratio even higher than that of PTT alone (∼94.4% vs ∼66.0%). Meanwhile, the NSS is highly biocompatible with rather low in vitro/in vivo toxicity and high stability, at variance with easily oxidized Bi2Se3 nanoagents reported previously. Such biocompatible single-component theranostic nanoagents produced by a facile synthesis and highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials for clinical antitumor applications. This highly porous nanostructure with a large fraction of void space may allow versatile use of the NSS, for example, in catalysis, gas sensing, and energy storage, in addition to accommodating drugs and other biomolecules.

Highly porous PEGylated Bi2S3 nano-urchins as a versatile platform for in vivo triple-modal imaging, photothermal therapy and drug delivery.

Biocompatible single-component nanoplatforms simultaneously integrating multiple therapeutic functions with multiple imaging modes are desirable for anticancer treatments. Herein, elaborately-designed highly porous PEGylated bismuth sulfide nano-urchins (Bi2S3-PEG NUs) have been successfully synthesized by using Bi2O3 nanospheres as the sacrificial template via the hydrothermal process. It is demonstrated that the Bi2S3-PEG NUs possess high compatibility, stability, X-ray attenuation ability, near-infrared (NIR) absorbance and photothermal conversion capability, without noticeable toxicity. Based on both in vitro and in vivo results, the product shows excellent performance in highly effective photothermal therapy (PTT) guided by triple-modal imaging, including X-ray computed tomography (CT), and photoacoustic (PA) and infrared thermal (IRT) imaging, without noticeable toxicity in vivo. Importantly, the NUs are highly porous with a high specific surface area and copious mesopores, providing high loading capacity to accommodate drugs (or guest biomolecules) for further applications in chemotherapy and other additional functions. Doxorubicin is loaded as an example, showing a rather high loading capacity (∼37.9%) together with a bimodal on-demand pH/photothermal-sensitive drug release property. Such fascinating multifunctional nanoagents may have considerable applications in antitumor diagnosis and therapy in the clinic.

Three-Dimensional Polydopamine Functionalized Coiled Microfibrous Scaffolds Enhance Human Mesenchymal Stem Cells Colonization and Mild Myofibroblastic Differentiation.

Electrospinning has been widely applied for tissue engineering due to its versatility of fabricating extracellular matrix (ECM) mimicking fibrillar scaffolds. Yet there are still challenges such as that these two-dimensional (2D) tightly packed, hydrophobic fibers often hinder cell infiltration and cell-scaffold integration. In this study, polycaprolactone (PCL) was electrospun into a grounded coagulation bath collector, resulting in 3D coiled microfibers with in situ surface functionalization with hydrophilic, catecholic polydopamine (pDA). The 3D scaffolds showed biocompatibility and were well-integrated with human bone marrow derived human mesenchymal stem cells (hMSCs), with significantly higher cell penetration depth compared to that of the 2D PCL microfibers from traditional electrospinning. Further differentiation of human mesenchymal stem cells (hMSCs) into fibroblast phenotype in vitro indicates that, compared to the stiff, tightly packed, 2D scaffolds which aggravated myofibroblasts related activities, such as upregulated gene and protein expression of α-smooth muscle actin (α-SMA), 3D scaffolds induced milder myofibroblastic differentiation. The flexible 3D fibers further allowed contraction with the well-integrated, mechanically active myofibroblasts, monitored under live-cell imaging, whereas the stiff 2D scaffolds restricted that.

Synergistic effect of topography, surface chemistry and conductivity of the electrospun nanofibrous scaffold on cellular response of PC12 cells.

Electrospun nanofibrous nerve implants is a promising therapy for peripheral nerve injury, and its performance can be tailored by chemical cues, topographical features as well as electrical properties. In this paper, a surface modified, electrically conductive, aligned nanofibrous scaffold composed of poly (lactic acid) (PLA) and polypyrrole (Ppy), referred to as o-PLAPpy_A, was fabricated for nerve regeneration. The morphology, surface chemistry and hydrophilicity of nanofibers were characterized by Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle, respectively. The effects of these nanofibers on neuronal differentiation using PC12 cells were evaluated. A hydrophilic surface was created by Poly-ornithine coating, which was able to provide a better environment for cell attachment, and furthermore aligned fibers were proved to be able to guide PC12 cells grow along the fiber direction and be beneficial for neurite outgrowth. The cellular response of PC12 cells to pulsed electrical stimulation was evaluated by NF 200 and alpha tubulin expression, indicating that electrical stimulation with a voltage of 40mV could enhance the neurite outgrowth. The PC12 cells stimulated with electrical shock showed greater level of neurite outgrowth and smaller cell body size. Moreover, the PC12 cells under electrical stimulation showed better viability. In summary, the o-PLAPpy_A nanofibrous scaffold supported the attachment, proliferation and differentiation of PC12 cells in the absence of electrical stimulation, which could be potential candidate for nerve regeneration applications.

Synergistic Inhibitory Effect of Peptide-Organic Coassemblies on Amyloid Aggregation.

Inhibition of amyloid aggregation is important for developing potential therapeutic strategies of amyloid-related diseases. Herein, we report that the inhibition effect of a pristine peptide motif (KLVFF) can be significantly improved by introducing a terminal regulatory moiety (terpyridine). The molecular-level observations by using scanning tunneling microscopy reveal stoichiometry-dependent polymorphism of the coassembly structures, which originates from the terminal interactions of peptide with organic modulator moieties and can be attributed to the secondary structures of peptides and conformations of the organic molecules. Furthermore, the polymorphism of the peptide-organic coassemblies is shown to be correlated to distinctively different inhibition effects on amyloid-ß 42 (Aß42) aggregations and cytotoxicity.

Multifunctional Bismuth Selenide Nanocomposites for Antitumor Thermo-Chemotherapy and Imaging.

To integrate real-time monitoring and therapeutic functions into a single nanoagent, we have designed and synthesized a drug-delivery platform based on a polydopamine(PDA)/human serum albumin (HSA)/doxorubicin (DOX) coated bismuth selenide (Bi2Se3) nanoparticle (NP). The resultant product exhibits high stability and biocompatibility both in vitro and in vivo. In addition to the excellent capability for both X-ray computed tomography (CT) and infrared thermal imaging, the NPs possess strong near-infrared (NIR) absorbance, and high capability and stability of photothermal conversion for efficient photothermal therapy (PTT) applications. Furthermore, a bimodal on-demand pH/photothermal-sensitive drug release has been achieved, resulting in a significant chemotherapeutic effect. Most importantly, the tumor-growth inhibition ratio achieved from thermo-chemotherapy of the Bi2Se3@PDA/DOX/HSA NPs was 92.6%, in comparison to the chemotherapy (27.8%) or PTT (73.6%) alone, showing a superior synergistic therapeutic effect. In addition, there is no noticeable toxicity induced by the NPs in vivo. This multifunctional platform is, therefore, promising for effective, safe and precise antitumor treatment and may stimulate interest in further exploration of drug loading on Bi2Se3 and other competent PTT agents combined with in situ imaging for biomedical applications.