Red/Near‐Infrared Emissive Metalloporphyrin‐Based Nanodots for Magnetic Resonance Imaging‐Guided Photodynamic Therapy In Vivo

Near‐infrared emissive (NIR) porphyrin‐implanted carbon nanodots (PCNDs or MPCNDs) are prepared by selectively carbonization of free base or metal complexes [M = Zn(II) or Mn(III)] of tetra‐(meso‐aminophenyl)porphyrin in the presence of citric acid. The as‐prepared nanodots exhibit spontaneously NIR emission, small size, good aqueous dispersibility, and favorable biocompatibility characteristic of both porphyrins and pristine carbon nanodots. The subcellular localization experiment of nanodots indicates a lysosome‐targeting feature. And the in vitro photodynamic therapy (PDT) results on HeLa cells indicate the nanodots alone have no adverse effect on tumor cells, but display remarkable photodynamic efficacy upon irradiation. Moreover, MnPCNDs containing paramagnetic Mn(III) ions, which possesses good biocompatibility, NIR luminescence, and magnetic resonance imaging and efficient singlet oxygen production, are further studied in magnetic resonance imaging‐guided photodynamic therapy in vivo.     

In Vivo Targeted Cancer Theranostics by Core/Shell‐Structured Multifunctional Prussian Blue/PLGA “Nanococktails”

The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy.     

Boosting Postsurgical Outcomes of Orthotopic Hepatocellular Carcinoma via an EpCAM‐Targeting Theranostic Nanoparticle

Hepatectomy is one of the main treatments for hepatocellular carcinoma (HCC). However, because microscopic tumor residues are often present after surgery, the recurrence rate of HCC remains extremely high. A multimodality imaging‐guided multifunctional nanoparticle, indocyanine‐green–gadolinium–copper sulfide@bovine‐serum‐albumin–epithelial‐cell‐adhesion molecule (EpCAM), is developed for HCC treatment based on a novel theranostic strategy. After intravenous injection of these nanoparticles into HCC‐bearing mice, remarkably selective accumulation and highly efficient retention of the nanoparticles in tumor sites are observed. This is due to the EpCAM's specific targeting ability, which also results in enhanced HCC contrast in a tri‐modal visualization, which unites magnetic resonance, photoacoustic, and fluorescence imaging. Moreover, nanoparticle uptake into the HCC allows photothermal therapy (PTT) as an interoperative adjuvant strategy for further eliminating possible microscopic residues and boosting HCC surgery outcomes. This theranostic strategy not only helps with precise diagnosis of HCC but enables intraoperatively imaging guidance for accurate tumor resection. Moreover, postoperation longitudinal observation demonstrates that intraoperative imaging‐guided resection alongside a PTT‐integrated treatment strategy can result in a significant improvement of overall survival rate. These multifunctional EpCAM‐targeting nanoparticles may respresent a novel theranostic strategy to improve postsurgical HCC treatment.     

Highly Ligand‐Directed and Size‐Dependent Photothermal Properties of Magnetite Particles

The development of cancer photothermal therapies, many of which rely on photothermal agents, has received significant attention in recent years. In this work, various ligands‐stabilized magnetite (Fe₃O₄) particles are fabricated and utilized as a photothermal agents for in vivo tumor‐imaging‐guided photothermal therapy. Fe₃O₄ particles stabilized by macromolecular ligands as, e.g. polyethylene glycol (PEG), exhibit a superior and more stable photothermal effect compared to Fe₃O₄ particles stabilized by small molecules like citrate, due to their stronger ability of antioxidation. In addition, the photothermal effect of Fe₃O₄ particles is revealed to increase with size, which is attributed to the redshift of Vis‐NIR spectra. Fe₃O₄ particles injected intravenously into mice can be accumulated in the tumor by the application of an external magnetic field, as revealed by magnetic resonance imaging. In vivo photothermal therapy test of PEG‐stabilized Fe₃O₄ further achieves better tumor ablation effect. Overall, this study demonstrates efficient imaging‐guided photothermal therapy of cancer that is based on Fe₃O₄ particles of optimized size and with optimized ligands. It is expected that the ligand‐directed and size‐dependent photothermal effect will provide more approaches in the design of novel materials.     

Photothermal/Photodynamic Therapy with Immune‐Adjuvant Liposomal Complexes for Effective Gastric Cancer Therapy

A diagnosis and therapeutic strategy for gastric cancer is developed herein by combining thermosensitive liposomal (TSL)‐based photothermal/photodynamics therapy (PTT/PDT) with chemotherapy and adjuvant immunotherapy. IR820, a photothermal agent, paclitaxel (PTX), an antitumor drug, and imiquimod (R837), a Toll‐like‐receptor‐7 agonist, are coencapsulated into a TSL drug delivery system. These formed PTX‐R837‐IR820@TSL complexes exhibit excellent optical properties, good dispersibility, and stability. Under NIR light irradiation, the measurement of singlet oxygen production and thermal efficiency indicate promising potential of PTX‐R837‐IR820@TSL complexes for PTT and PDT. Confocal microscopy and small animal NIR imaging demonstrate tumor targeting ability of the liposomal complexes to gastric cancer cells. In vitro cell viability assays and in vivo animal experiments show prominent antitumor efficiency of PTX‐R837‐IR820@TSL complexes upon NIR light irradiation. This excellent therapeutic efficacy is attributed to the simultaneous chemotherapy and PTT/PDT. Furthermore, the liposomal complexes under NIR irradiation would ablate tumors to generate a pool of tumor‐associated antigens, which is able to promote strong antitumor immune responses in the presence of those R837‐containing liposomal complexes acted as adjuvant. These results indicate that the multifunctional liposomal complexes could realize a remarkable synergistic therapeutic outcome in gastric carcinoma.     

Tumor‐Targeting W18O49 Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W₁₈O₄₉‐17AAG) comprising carboxyl‐group‐functionalized W₁₈O₄₉ nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W₁₈O₄₉ nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W₁₈O₄₉ nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W₁₈O₄₉‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted.     

Upconverting nanoparticles for pre‐clinical diffuse optical imaging,microscopy and sensing: Current trends and future challenges

Upconverting nanoparticles (UCNPs) are a class of recently developed luminescent biomarkers that – in several aspects – are superior to organic dyes and quantum dots. UCNPs can emit spectrally narrow anti‐Stokes shifted light with quantum yields which greatly exceed those of two‐photon dyes for fluence rates relevant for deep tissue imaging. Compared with conventionally used Stokes‐shifting fluorophores, UCNP‐based imaging systems can acquire completely autofluorescence‐free data with superb contrast. For diffuse optical imaging, the multi‐photon process involved in the upconversion process can be used to obtain images with unprecedented resolution. These unique properties make UCNPs extremely attractive in the field of biophotonics. UCNPs have already been applied in microscopy, small‐animal imaging, multi‐modal imaging, highly sensitive bioassays, temperature sensing and photodynamic therapy. In this review, the current state‐of‐the‐art UCNPs and their applications for diffuse imaging, microscopy and sensing targeted towards solving essential biological issues are discussed.     

Carbon Dots‐Cluster‐DOX Nanocomposites Fabricated by a Co‐Self‐Assembly Strategy for Tumor‐Targeted Bioimaging and Therapy

Carbon‐based nanomaterials could afford versatile potential applications in biomedical optical imaging and as nanoparticle drug carriers, owing to their promising optical and biocompatible capabilities. In this paper, it is first found that amphipathic cetylpyridinium chloride (CPC)‐stabilized oil‐soluble carbon dots (CDs) could self‐assemble into hydrophilic CDs clusters with hydrophobic core under ultrasound, in which CPC acts as carbon source, stabilizer, and phase transfer agent. Next, the size‐control (for size‐dependent passive tumor targeting) and doxorubicin (DOX) uploading of aqueous CDs clusters, and subsequent surface charge modification via overcoating with cRGD‐ and octylamine‐modified polyacrylic acid (cRGD‐PAA‐OA) (reversing their surface charges into negative and introducing active tumor‐targeting ability) are explored systematically. Based on this sequential administration mode, CDs‐cluster‐DOX/cRGD‐PAA‐OA nanocomposites exhibit selective human malignant glioma cell line (U87MG) tumor targeting. In in vitro drug release experiments, the nanocomposites could release DOX timely. Owning to the dual tumor targeting effects and seasonable drug release, CDs‐cluster‐DOX/cRGD‐PAA‐OA show remarkably tumor targetability and enhanced antitumor efficacy (and reduced adverse reaction), comparing to free DOX in animal models. These results indicate that fabricating nanocomposite via co‐self‐assembly strategy is efficient toward drug delivery system for tumor‐targeting theranostic.     

Synergistic Effect of Thermo‐Radiotherapy Using Au@FeS Core–Shell Nanoparticles as Multifunctional Therapeutic Nanoagents

Imaging guided combined therapy has attracted great attention in recent years. This study develops core–shell Au@FeS nanoparticles with polyethylene glycol (PEG) coating as multifunctional nanotheranostic agent for tumor imaging and combined photothermal therapy (PTT) and radiotherapy (RT). In this Au@FeS nanostructure, the gold core can act as a radiosensitizer for enhanced RT, while FeS shell offers contrast for T2‐weighted magnetic resonance imaging and endows the nanoparticles with strong high near‐infrared (NIR) for photoacoustic imaging and PTT. As demonstrated by both in vitro and in vivo experiments, Au@FeS‐PEG can act as excellent therapeutic agent for cancer synergistic treatment. More importantly, mild PTT boosts the blood flow into tumor and increases oxygenation to overcome the tumor hypoxia microenvironment, further enhancing the efficacy of RT. Moreover, Au@FeS‐PEG induces on obvious toxicity at a high dose (20 mg kg^?1) to the treated mice as evidenced by blood biochemistry. Therefore, this study brings an excellent strategy for cancer enhanced RT through NIR‐triggered mild PTT to overcome hypoxia‐associated radioresistance.     

Peptide‐Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer

Targeted drug delivery using epidermal growth factor peptide‐targeted gold nanoparticles (EGF_pep‐Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGF_pep‐Au NP‐Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGF_pep‐Au NP‐Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGF_pep‐Au NP‐Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGF_pep‐Au NP‐Pc 4 results in interrupted tumor growth when compared with EGF_pep‐Au NP control mice when selectively activated with light. These data demonstrate that EGF_pep‐Au NP‐Pc 4 utilizes cancer‐specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery.     

Multivalent Sorbitol Probes for Near-Infrared Photothermal Cancer Therapy

Photothermal therapy (PTT) is a targeted and non-invasive therapeutic strategy for effective cancer treatment. Image-guided PTT based on bifunctional near-infrared (NIR) fluorophores has received significant attention recently and the development of NIR fluorophores is advised for targeted imaging and precise cancer therapy. In this study, a multivalent sorbitol-conjugated NIR fluorophore (4Sorbitol-800) is used as a photothermal therapeutic agent for in vivo cancer imaging and therapy because of the high tumor-targetability of the sorbitol moieties and excellent photothermal properties of the NIR heptamethine cyanine core. This NIR fluorophore demonstrates an excellent photothermal effect, which increases the temperature of the tumor by 57.4 °C upon NIR laser irradiation (1.1 W cm⁻²) for 5 min. The volumes of HT-29 tumors targeted by 4Sorbitol-800 significantly decrease over 7 days after photothermal treatment. The 4Sorbitol-800 developed in this study exhibits good in vivo safety and a highly efficient antitumor capability. Therefore, 4Sorbitol-800 in combination with NIR laser irradiation has promising potential for future clinical applications with targeted photothermal cancer therapy.     

Recent Advancements in Ln‐Ion‐Based Upconverting Nanomaterials and Their Biological Applications

Upconversion nanoparticles (UCNPs) convert low‐energy infrared (IR) or near‐infrared (NIR) photons into high‐energy emission radiation ranging from ultraviolet to visible through a photon upconversion process. In comparison to conventional fluorophores, such as organic dyes or semiconductor quantum dots, lanthanide‐ion‐doped UCNPs exhibit high photostability, no photoblinking, no photobleaching, low cytotoxicity, sharp emission lines, and long luminescent lifetimes. Additionally, the use of IR or NIR for excitation in such UCNPs reduces the autofluorescence background and enables deeper penetration into biological samples due to reduced light scattering with negligible damage to the samples. Because of these attributes, UCNPs have found numerous potential applications in biological and medicinal fields as novel fluorescent materials. Different upconversion mechanisms commonly observed in UCNPs, various methods that are used in their synthesis, and surface modification processes are discussed. Recent applications of Ln‐UCNPs in the biological and medicinal fields, including in vivo and in vitro biological imaging, multimodal imaging, photodynamic therapy, drug delivery, and antibacterial activity, are also presented.     

Self‐Assemble Polymeric Nanoparticle with GSH Exhaustion for SPECT Imaging–Guided Enhanced Radioisotope Therapy

Exploiting biocompatible nanomaterials for cancer theranostics has attracted great attention in recent years. Herein, a multifunctional self‐assembled nanoparticle based on a biocompatible polymer that contains 3‐(4‐hydroxyphenyl) propionic acid N‐hydroxysuccinimide ester (HOPA) for radiolabeling and piperlongumine (PL) for exhausting endogenous glutathione (GSH) (HOPA‐C18PMH‐PEG/PL) is successfully synthesized. With radionuclide ¹²⁵I labeling, SPECT imaging shows high tumor uptake of HOPA‐C18PMH‐PEG/PL after intravenous injection. The in vitro and in vivo combined radioisotope therapy (RIT) and chemotherapy using ¹³¹I‐labeled HOPA‐C18PMH‐PEG/PL is then carried out, achieving synergistic antitumor effect. This is because the reactive oxygen species (ROS) level in the tumor sites of mice treated with ¹³¹I‐labeled HOPA‐C18PMH‐PEG/PL is increased after the exhaustion of GSH by PL. Additionally, such a strategy (exhausting GSH and increasing ROS) induces no obvious toxicity to normal tissue. Therefore, as‐made polymeric nanoparticles exhibit multifunctional properties for SPECT imaging–guided combined RIT and chemotherapy in one system. This finding will further promote polymeric nanoparticle–based RIT of cancer and is expected to be used for future clinical transformation.     

Human‐Serum‐Albumin‐Coated Prussian Blue Nanoparticles as pH‐/Thermotriggered Drug‐Delivery Vehicles for Cancer Thermochemotherapy

Constructing novel multimodal antitumor therapeutic nanoagents has attracted tremendous recent attention. In this work, a new drug‐delivery vehicle based on human‐serum‐albumin (HSA)‐coated Prussian blue nanoparticles (PB NPs) is synthesized. It is demonstrated that doxorubicin (DOX)/HSA is successfully loaded after in situ polymerization of dopamine onto PB NPs, and the PB@PDA/DOX/HSA NPs are highly compatible and stable in various physiological solutions. The NPs possess strong near‐infrared (NIR) absorbance, and excellent capability and stability of photothermal conversion for highly efficient photothermal therapy applications. Furthermore, a bimodal on‐demand drug release sensitively triggered by pH or NIR irradiation has been realized, resulting in a significant chemotherapeutic effect due to the preferential uptake and internalization of the NPs by cancer cells. Importantly, the thermochemotherapy efficacy of the NPs has been examined by a cell viability assay, revealing a remarkably superior synergistic anticancer effect over either monotherapy. Such multifunctional drug‐delivery systems composed of approved materials may have promising biomedical applications for antitumor therapy.     

Synchrotron X‐ray microbeam dosimetry with a 20 micrometre resolution scintillator fibre‐optic dosimeter

Cancer is one of the leading causes of death worldwide. External beam radiation therapy is one of the most important modalities for the treatment of cancers. Synchrotron microbeam radiation therapy (MRT) is a novel pre‐clinical therapy that uses highly spatially fractionated X‐ray beams to target tumours, allowing doses much higher than conventional radiotherapies to be delivered. A dosimeter with a high spatial resolution is required to provide the appropriate quality assurance for MRT. This work presents a plastic scintillator fibre optic dosimeter with a one‐dimensional spatial resolution of 20 µm, an improvement on the dosimeter with a resolution of 50 µm that was demonstrated in previous work. The ability of this probe to resolve microbeams of width 50 µm has been demonstrated. The major limitations of this method were identified, most notably the low‐light signal resulting from the small sensitive volume, which made valley dose measurements very challenging. A titanium‐based reflective paint was used as a coating on the probe to improve the light collection, but a possible effect of the high‐Z material on the probes water‐equivalence has been identified. The effect of the reflective paint was a 28.5 ± 4.6% increase in the total light collected; it did not affect the shape of the depth‐dose profile, nor did it explain an over‐response observed when used to probe at low depths, when compared with an ionization chamber. With improvements to the data acquisition, this probe design has the potential to provide a water‐equivalent, inexpensive dosimetry tool for MRT.     

A Functionalized Hollow Mesoporous Silica Nanoparticles‐Based Controlled Dual‐Drug Delivery System for Improved Tumor Cell Cytotoxicity

Multifunctional nanoparticles for selectively targeting tumor cells and effectively delivering multiple drugs are urgently needed in cancer therapy. Here, a dual‐drug delivery system is prepared, based on functionalized hollow mesoporous silica nanoparticles (HMSNs). Doxorubicin (DOX) hydrochloride is loaded into the hollow core, and dichloro(1,2‐diaminocyclohexane)platinum (II) (DACHPt) is stored in the pores of the shell by the coordination interaction with the carboxyl groups modified on the pore walls, which also serves as barriers to control the DOX release. Detailed studies in vitro indicate that the DACHPt release is triggered by Cl^? through the cleavage of the coordination interaction, and the DOX release depends on the release rate of DACHPt and the environmental pH value. The surface of the mechanized nanoparticles is also modified by transferrin (Tf) to achieve the tumor specificity. Compared with individual drug delivery systems, the dual‐drug delivery system shows synergistic efficacy on the cell cytotoxicity (combination index = 0.30), resulting in improved tumor cell killing. The present dual‐drug delivery system provides a promising strategy to develop controlled and targeted combination therapies for efficient cancer treatment.     

Silicon quantum dots delivered phthalocyanine for fluorescence guided photodynamic therapy of tumor

Imaging-guided cancer therapy provides a simultaneous tumor imaging and treatment, which helps to eliminate the excessive toxicity to the healthy tissues. For this purpose, multifunctional probes capable of both imaging and curing are needed. In this work, we synthesize water-soluble silicon quantum dots(Si QDs) smaller than 5 nm. Such Si QDs are used for delivering the hydrophobic drug phthalocyanine(Pc). The as-prepared Si/Pc nanocomposite particles show efficient transmembrane delivery into cells and feasible biocompatibility. Moreover, these composite particles emit dualchannel fluorescence signals even after cellular internalization and demonstrate robust photostability in the Si channel.More interestingly, the Si/Pc composite particles show efficient photodynamic therapy effects against tumors both in vitro and in vivo.     

Development of a Liver‐Targeting Gold–PEG–Galactose Nanoparticle Platform and a Structure–Function Study

For the specific liver parenchymal cell delivery, a series of short heterobifunctional poly(ethylene glycol) (PEG) derivatives containing dimercapto and galactose (Gal) terminals is synthesized for the preparation of gold conjugates. The Gal density on the surface of all gold conjugates can be well controlled and the prepared gold conjugates are stable in various media, even in the presence of serum. For the liver targeting and reflectance imaging applications, the structure–function relationships of this platform, including the influence of the PEG molecular weight and the Gal ligand coverage of hybrid particles on the cytotoxicity and cellular recognition of tumor cells in vitro and on their liver‐targeting ability in small animals, are studied. Biocompatibility results show that HepG2 cells are more sensitive than HeLa cells to gold conjugates. Cellular uptake studies demonstrate that a lower PEG molecular weight, a higher Gal density, or a higher gold concentration can increase the cellular uptake efficiency of these hybrid particles in HepG2 cells when the other parameters are constant. The results reveal the importance of parameter modulation for the design and control of nanoprobes and the gold conjugates with short PEG chains and a high Gal density are a potential vector for active‐targeting therapy.     

Synergistic Effect of Photothermal Therapy and Chemotherapy Using Camptothecin‐Conjugated Gold Nanorods

A combinatorial treatment comprising thermal therapy and chemotherapy offers synergistic effects by inducing localized heat to targeted tumor sites and simultaneously delivering anticancer drugs to minimize systemic side effects and enhance the cytotoxic effect. In this study, a novel platform is developed for combining photothermal therapy and chemotherapy using drug‐conjugated gold nanorods (GNRs). Camptothecin (CPT), a model anticancer drug, is chemically conjugated onto GNRs through hydrolytic ester bonding. Upon near‐infrared (NIR) irradiation, localized heat from GNRs in target areas starts to destroy tissues and cells via photothermal therapy, and the elevated temperature accelerates hydrolysis of ester linkage, rapidly releasing drugs for chemotherapy. This combined NIR triggered thermal therapy and chemotherapy with CPT‐functionalized GNRs (CPT‐GNRs) presents a synergistic effect that has high efficacy in in vitro tests, thus providing a robust platform for efficient cancer treatments.     

Core–Shell Bi2Se3@mSiO2‐PEG as a Multifunctional Drug‐Delivery Nanoplatform for Synergistic Thermo‐Chemotherapy with Infrared Thermal Imaging of Cancer Cells

Thermo‐chemotherapy combining photothermal therapy (PTT) with chemotherapy has become a potent approach for antitumor treatment. In this study, a multifunctional drug‐delivery nanoplatform based on polyethylene glycol (PEG)‐modified mesoporous silica‐coated bismuth selenide nanoparticles (referred to as Bi₂Se₃@mSiO₂‐PEG NPs) is developed for synergistic PTT and chemotherapy with infrared thermal (IRT) imaging of cancer cells. The product shows no/low cytotoxicity, strong near‐infrared (NIR) optical absorption, high photothermal conversion capacity, and stability. Utilizing the prominent photothermal effect, high‐contrast IRT imaging and efficient photothermal killing effect on cancer cells are achieved upon NIR laser irradiation. Moreover, the successful mesoporous silica coating of the Bi₂Se₃@mSiO₂‐PEG NPs cannot only largely improve the stability but also endow the NPs high drug loading capacity. As a proof‐of‐concept model, doxorubicin (DOX) is successfully loaded into the NPs with rather high loading capacity (≈50.0%) via the nanoprecipitation method. It is found that the DOX‐loaded NPs exhibit a bimodal on‐demand pH‐ and NIR‐responsive drug release property, and can realize effective intracellular drug delivery for chemotherapy. The synergistic thermo‐chemotherapy results in a significantly higher antitumor efficacy than either PTT or chemotherapy alone. The work reveals the great potential of such core–shell NPs as a multifunctional drug‐delivery nanosystem for thermo‐chemotherapy.