Magnetic Targeting Enhanced Theranostic Strategy Based on Multimodal Imaging for Selective Ablation of Cancer

The booming development of nanomedicine offers great opportunities for cancer diagnostics and therapeutics. Herein, a magnetic targeting‐enhanced cancer theranostic strategy using a multifunctional magnetic‐plasmonic nano‐agent is developed, and a highly effective in vivo tumor photothermal therapy, which is carefully planed based on magnetic resonance (MR)/photoacoustic (PA) multimodal imaging, is realized. By applying an external magnetic field (MF) focused on the targeted tumor, a magnetic targeting mediated enhanced permeability and retention (MT‐EPR) effect is observed. While MR scanning provides tumor localization and reveals time‐dependent tumor homing of nanoparticles for therapeutic planning, photoacoustic imaging with higher spatial resolution allows noninvasive fine tumor margin delineation and vivid visualization of three dimensional distributions of theranostic nanoparticles inside the tumor. Utilizing the near‐infrared (NIR) plasmonic absorbance of those nanoparticles, selective photothermal tumor ablation, whose efficacy is predicted by real‐time infrared thermal imaging intra‐therapeutically, is carried out and then monitored by MR imaging for post‐treatment prognosis. Overall, this study illustrates the concept of imaging‐guided MF‐targeted photothermal therapy based on a multifunctional nano‐agent, aiming at optimizing therapeutic planning to achieve the most efficient cancer therapy.     

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

A New Single 808 nm NIR Light‐Induced Imaging‐Guided Multifunctional Cancer Therapy Platform

The NIR light‐induced imaging‐guided cancer therapy is a promising route in the targeting cancer therapy field. However, up to now, the existing single‐modality light‐induced imaging effects are not enough to meet the higher diagnosis requirement. Thus, the multifunctional cancer therapy platform with multimode light‐induced imaging effects is highly desirable. In this work, captopril stabilized‐Au nanoclusters Au₂₅(Capt)₁₈?(Au₂₅) are assembled into the mesoporous silica shell coating outside of Nd³⁺‐sensitized upconversion nanoparticles (UCNPs) for the first time. The newly formed Au₂₅ shell exhibits considerable photothermal effects, bringing about the photothermal imaging and photoacoustic imaging properties, which couple with the upconversion luminescence imaging. More importantly, the three light‐induced imaging effects can be simultaneously achieved by exciting with a single NIR light (808 nm), which is also the triggering factor for the photothermal and photodynamic cancer therapy. Besides, the nanoparticles can also present the magnetic resonance and computer tomography imaging effects due to the Gd³⁺ and Yb³⁺ ions in the UCNPs. Furthermore, due to the photodynamic and the photothermal effects, the nanoparticles possess efficient in vivo tumor growth inhibition under the single irradiation of 808 nm light. The multifunctional cancer therapy platform with multimode imaging effects realizes a true sense of light‐induced imaging‐guided cancer therapy.     

Tantalum Sulfide Nanosheets as a Theranostic Nanoplatform for Computed Tomography Imaging‐Guided Combinatorial Chemo‐Photothermal Therapy

Near‐infrared (NIR)‐absorbing metal‐based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal‐controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta‐derived nanomaterials represent promising candidates for biomedical applications. However, Ta‐based nanomaterials by themselves have not been explored for NIR‐mediated photothermal ablation therapy. In this work, an innovative Ta‐based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS₂) nanosheets (NSs) is reported for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS₂ NSs exhibit multiple unique features including (i) efficient NIR light‐to‐heat conversion with a high photothermal conversion efficiency of 39%, (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat‐enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. It is expected that this multifunctional NS platform can serve as a promising candidate for imaging‐guided cancer therapy and selection of cancer patients with high tumor accumulation.     

Mesoporous Silica Coated Single‐Walled Carbon Nanotubes as a Multifunctional Light‐Responsive Platform for Cancer Combination Therapy

The development of cancer combination therapies, many of which rely on nanoscale theranostic agents, has received increasing attention in recent years. In this work, polyethylene glycol (PEG) modified mesoporous silica (MS) coated single‐walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging guided combination therapy of cancer. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the mesoporous structure of the obtained SWNT@MS‐PEG nano‐carriers with high efficiency. Upon stimulation under near‐infrared (NIR) light, photothermally triggered drug release from DOX loaded SWNT@MS‐PEG is observed inside cells, resulting in a synergistic cancer cell killing effect. As revealed by both photoacoustic (PA) and magnetic resonance (MR) imaging, we further uncover efficient tumor accumulation of SWNT@MS‐PEG/DOX after intravenous injection into mice. In vivo combination therapy using this agent is further demonstrated in a mouse tumor model, achieving a remarkable synergistic anti‐tumor effect superior to that obtained by mono‐therapy. Our work presents a new type of theranostic nano‐platform, which could load therapeutic molecules with high efficiency, be responsive to external NIR stimulation, and at the same time serve as a diagnostic imaging agent.     

Bottom‐Up Preparation of Uniform Ultrathin Rhenium Disulfide Nanosheets for Image‐Guided Photothermal Radiotherapy

Facile preparation of multifunctional theranostic nanoplatforms with well‐controlled morphology and sizes remains an attractive in the area of nanomedicine. Here, a new kind of 2D transition metal dichalcogenide, rhenium disulfide (ReS₂) nanosheets, with uniform sizes, strong near‐infrared (NIR) light, and strong X‐ray attenuation, is successfully synthesized. After surface modification with poly(ethylene glycol) (PEG), the synthesized ReS₂‐PEG nanosheets are stable in various physiological solutions. In addition to their contrasts in photoacoustic imaging and X‐ray computed tomography imaging because of their strong NIR light and X‐ray absorptions, respectively, such ReS₂‐PEG nanosheets can also be tracked under nuclear imaging after chelator‐free labeling with radioisotope ions, ^99mTc⁴⁺. Efficient tumor accumulation of ReS₂‐PEG nanosheets is then observed after intravenous injection into tumor‐bearing mice under triple‐modal imaging. The combined in vivo photothermal radiotherapy is further conducted, achieving a remarkable synergistic tumor destruction effect. Finally, no obvious toxicity of ReS₂‐PEG nanosheets is observed from the treated mice within 30 d. This work suggests that such ultrathin ReS₂ nanosheets with well‐controlled morphology and uniform sizes may be a promising type of multifunctional theranostic agent for remotely triggered cancer combination therapy.     

Near‐Infrared Absorbing Polymeric Nanoparticles as a Versatile Drug Carrier for Cancer Combination Therapy

Poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) nanoparticles, after being coated with polyethylene glycol (PEG), are used as a drug carrier to load various types of aromatic therapeutic molecules, including chemotherapy drugs doxorubicin (DOX) and SN38, as well as a photodynamic agent chlorin e6 (Ce6), through π–π stacking and hydrophobic interaction. Interesting functionalities of PEDOT:PSS‐PEG as an unique versatile drug delivery platform are discovered. Firstly, for water‐insoluble drugs such as SN38, the loading on PEDOT:PSS‐PEG dramatically enhances its water solubility, while maintaining its cytotoxicity to cancer cells. Secondly, the delivery of Ce6 by PEDOT:PSS‐PEG is able to remarkably accelerate the cellular uptake of Ce6 molecules, and thus offers improved photodynamic therapeutic efficacy. Using DOX‐loaded PEDOT:PSS‐PEG as the model system, it is demonstrated that the photothermal effect of PEDOT:PSS‐PEG can be utilized to promote the delivery of this chemotherapeutic agent, achieving a combined photothermal‐ and chemotherapy with an obvious synergistic cancer killing effect. Moreover, it is also shown that multiple types of therapeutic agents could be simultaneously loaded on PEDOT:PSS‐PEG nanoparticles and delivered into cancer cells. This work highlights the great potential of NIR‐absorbing polymeric nanoparticles as multifunctional drug carriers for potential cancer combination therapy with high efficacy.     

Design and Synthesis of “All‐in‐One” Multifunctional FeS2 Nanoparticles for Magnetic Resonance and Near‐Infrared Imaging Guided Photothermal Therapy of Tumors

The ideal theranostic nanoplatform for tumors is a single nanoparticle that has a single semiconductor or metal component and contains all multimodel imaging and therapy abilities. The design and preparation of such a nanoparticle remains a serious challenge. Here, with FeS₂ as a model of a semiconductor, the tuning of vacancy concentrations for obtaining “all‐in‐one” type FeS₂ nanoparticles is reported. FeS₂ nanoparticles with size of ≈30 nm have decreased photoabsorption intensity from the visible to near‐infrared (NIR) region, due to a low S vacancy concentration. By tuning their shape/size and then enhancing the S vacancy concentration, the photoabsorption intensity of FeS₂ nanoparticles with size of ≈350 nm (FeS₂‐350) goes up with the increase of the wavelength from 550 to 950 nm, conferring the high NIR photothermal effect for thermal imaging. Furthermore, this nanoparticle has excellent magnetic properties for T₂‐weighted magnetic resonance imaging (MRI). Subsequently, FeS₂‐350 phosphate buffer saline (PBS) dispersion is injected into the tumor‐bearing mice. Under the irradiation of 915‐nm laser, the tumor can be ablated and the metastasis lesions in liver suffer significant inhibition. Therefore, FeS₂‐350 has great potential to be used as novel “all‐in‐one” multifunctional theranostic nanoagents for MRI and NIR dual‐modal imaging guided NIR‐photothermal ablation therapy (PAT) of tumors.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.     

All‐in‐One Phototheranostics: Single Laser Triggers NIR‐II Fluorescence/Photoacoustic Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Development of single near‐infrared (NIR) laser triggered phototheranostics for multimodal imaging guided combination therapy is highly desirable but is still a big challenge. Herein, a novel small‐molecule dye DPP‐BT is designed and synthesized, which shows strong absorption in the first NIR window (NIR‐I) and fluorescence emission in the second NIR region (NIR‐II). Such a dye not only acts as a dual‐modal contrast agent for NIR‐II fluorescence and photoacoustic (PA) imaging, but also serves as a combined therapeutic agent for photothermal therapy (PTT) and photodynamic therapy (PDT). The single NIR laser triggered all‐in‐one phototheranostic nanoparticles are constructed by encapsulating the dye DPP‐BT, chemotherapy drug DOX, and natural phase‐change materials with a folic acid functionalized amphiphile. Notably, under NIR laser irradiation, DOX can effectively release from such nanoparticles via NIR‐induced hyperthermia of DPP‐BT. By intravenous injection of such nanoparticles into Hela tumor‐bearing mice, the tumor size and location can be accurately observed via NIR‐II fluorescence/PA dual‐modal imaging. From in vitro and in vivo therapy results, such nanoparticles simultaneously present remarkable antitumor efficacy by PTT/PDT/chemo combination therapy, which is triggered by a single NIR laser. Overall, this work provides an innovative strategy to design and construct all‐in‐one nanoplatforms for clinical phototheranostics.     

Tumor‐Penetrating Nanotherapeutics Loading a Near‐Infrared Probe Inhibit Growth and Metastasis of Breast Cancer

The tumor growth and metastasis is the leading reason for the high mortality of breast cancer. Herein, it is first reported a deep tumor‐penetrating photothermal nanotherapeutics loading a near‐infrared (NIR) probe for potential photothermal therapy (PTT) of tumor growth and metastasis of breast cancer. The NIR probe of 1,1‐dioctadecyl‐3,3,3,3‐tetramethylindotricarbocyanine iodide (DiR), a lipophilicfluorescent carbocyanine dye with strong light‐absorbing capability, is entrapped into the photothermal nanotherapeutics for PTT application. The DiR‐loaded photothermal nanotherapeutics (DPN) is homogeneous nanometer‐sized particles with the mean diameter of 24.5 ± 4.1 nm. Upon 808 nm laser irradiation, DPN presents superior production of thermal energy than free DiR both in vitro and in vivo. The cell proliferation and migration activities of metastatic 4T1 breast cancer cells are obviously inhibited by DPN in combination with NIR irradiation. Moreover, DPN can induce a higher accumulation in tumor and penetrate into the deep interior of tumor tissues. The in vivo PTT measurements indicate that the growth and metastasis of breast cancer are entirely inhibited by a single treatment of DPN with NIR irradiation. Therefore, the deep tumor‐penetrating DPN can provide a promising strategy for PTT of tumor progression and metastasis of breast cancer.     

Imaging‐Guided pH‐Sensitive Photodynamic Therapy Using Charge Reversible Upconversion Nanoparticles under Near‐Infrared Light

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) can effectively destroy cancer cells under tissue‐penetrating near‐infrared light (NIR) light. Herein, we synthesize manganese (Mn²⁺)‐doped UCNPs with strong red light emission at ca. 660 nm under 980 nm NIR excitation to activate Chlorin e6 (Ce6), producing singlet oxygen (¹O₂) to kill cancer cells. A layer‐by‐layer (LbL) self‐assembly strategy is employed to load multiple layers of Ce6 conjugated polymers onto UCNPs via electrostatic interactions. UCNPs with two layers of Ce6 loading (UCNP@2xCe6) are found to be optimal in terms of Ce6 loading and ¹O₂ generation. By further coating UCNP@2xCe6 with an outer layer of charge‐reversible polymer containing dimethylmaleic acid (DMMA) groups and polyethylene glycol (PEG) chains, we obtain a UCNP@2xCe6‐DMMA‐PEG nanocomplex, the surface of which is negatively charged and PEG coated under pH 7.4; this could be converted to have a positively charged naked surface at pH 6.8, significantly enhancing cell internalization of nanoparticles and increasing in vitro NIR‐induced PDT efficacy. We then utilize the intrinsic optical and paramagnetic properties of Mn²⁺‐doped UCNPs for in vivo dual modal imaging, and uncover an enhanced retention of UCNP@2xCe6‐DMMA‐PEG inside the tumor after intratumoral injection, owing to the slightly acidic tumor microenvironment. Consequently, a significantly improved in vivo PDT therapeutic effect is achieved using our charge‐reversible UCNP@2xCe6‐DMMA‐PEG nanoparticles. Finally, we further demonstrate the remarkably enhanced tumor‐homing of these pH‐responsive charge‐switchable nanoparticles in comparison to a control counterpart without pH sensitivity after systemic intravenous injection. Our results suggest that UCNPs with finely designed surface coatings could serve as smart pH‐responsive PDT agents promising in cancer theranostics.     

PEGylated Polypyrrole Nanoparticles Conjugating Gadolinium Chelates for Dual‐Modal MRI/Photoacoustic Imaging Guided Photothermal Therapy of Cancer

Polypyrrole nanoparticles conjugating gadolinium chelates were successfully fabricated for dual‐modal magnetic resonance imaging (MRI) and photoacoustic imaging guided photothermal therapy of cancer, from a mixture of pyrrole and pyrrole‐1‐propanoic acid through a facile one‐step aqueous dispersion polymerization, followed by covalent attachment of gadolinium chelate, using polyethylene glycol as a linker. The obtained PEGylated poly­pyrrole nanoparticles conjugating gadolinium chelates (Gd‐PEG‐PPy NPs), sized around around 70 nm, exhibited a high T₁ relaxivity coefficient of 10.61 L mm ^?1 s^?1, more than twice as high as that of the relating free Gd³⁺ complex (4.2 L mm ^–1 s^?1). After 24 h intravenous injection of Gd‐PEG‐PPy NPs, the tumor sites exhibited obvious enhancement in both T₁‐weighted MRI intensity and photoacoustic signal compared with that before injection, indicating the efficient accumulation of Gd‐PEG‐PPy NPs due to the introduction of the PEG layer onto the particle surface. In addition, tumor growth could be effectively inhibited after treatment with Gd‐PEG‐PPy NPs in combination with near‐infrared laser irradiation. The passive targeting and high MRI/photo­acoustic contrast capability of Gd‐PEG‐PPy NPs are quite favorable for precise cancer diagnosing and locating the tumor site to guide the external laser irradiation for photothermal ablation of tumors without damaging the surrounding healthy tissues. Therefore, Gd‐PEG‐PPy NPs may assist in better monitoring the therapeutic process, and contribute to developing more effective “personalized medicine,” showing great potential for cancer diagnosis and therapy.     

Bismuth Ferrite‐Based Nanoplatform Design: An Ablation Mechanism Study of Solid Tumor and NIR‐Triggered Photothermal/Photodynamic Combination Cancer Therapy

Although nanomaterial‐mediated phototherapy, in particular photothermal therapy (PTT) and photodynamic therapy (PDT), is extensively investigated in recent years, the ablation mechanism, evolution, and rehabilitation process of in vivo solid tumor after phototherapy are rarely explored yet and remain a terra incognita. Herein, a kind of bismuth ferrite nanoparticles (abbreviated as BFO NPs) are strategically designed and synthesized with a desirable size and bioactivity as a brand‐new phototherapeutic agent for the phototherapy, which are of strong near infrared (NIR) absorbance, excellent biocompatibility, and outstanding photophysical activity for the hyperthemia and reactive oxygen species generation. Resultantly, BFO NPs can realize simultaneous PTT/PDT synergistic therapy outcome against cancer cells and solid tumor under NIR laser irradiation. Meanwhile, for the first time, more attentions are paid to demonstrate ablation mechanism and evolution process of in vivo solid tumor after phototherapy by B‐mode ultrasonography/magnetic resonance imaging as well as histopathological analysis, all of which verify a series of physiological processes, being in order of necrosis of parenchymal cells, in situ tissue disintegration, liquefaction, and finally encapsulation process.     

“All‐in‐One” Nanoparticles for Trimodality Imaging‐Guided Intracellular Photo‐magnetic Hyperthermia Therapy under Intravenous Administration

Great efforts have been devoted so far to combine nano‐magnetic hyperthermia and nano‐photothermal therapy to achieve encouraging additive therapeutic performance in vitro and in vivo with limitation to direct intratumoral injection and no guidance of multimodality molecular imaging. In this study, a novel multifunctional theranostic nanoplatform (MNP@PES‐Cy7/2‐DG) consisting of magnetic nanoparticles (MNPs), poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PES), Cyanine7 (Cy7), and 2‐deoxyglucose (2‐DG)‐polyethylene glycol is developed. They are then applied to combined photo‐magnetic hyperthermia therapy under intravenous administration that is simultaneously guided by trimodality molecular imaging. Remarkably, nanoparticles are found aggregated mainly in the cytoplasm of tumor cells in vitro and in vivo, and exhibit stealth‐like behavior with a long second‐phase blood circulation half‐life of 20.38 ± 4.18 h. Under the guidance of photoacoustic/near‐infrared fluorescence/magnetic resonance trimodality imaging, tumors can be completely eliminated under intracellular photo‐magnetic hyperthermia therapy with additive therapeutic effect due to precise hyperthermia. This study may promote a further exploration of such a platform for clinical applications.     

Mesoporous Polydopamine Carrying Manganese Carbonyl Responds to Tumor Microenvironment for Multimodal Imaging‐Guided Cancer Therapy

Multifunctional nanodrugs integrating multiple therapeutic and imaging functions may find tremendous biomedical applications. However, the development of a simple yet potent theranostic nanosystem with a high payload and microenvironment responsiveness enhancing imaging‐guided cancer therapy is still a great challenge. Herein, a kind of MnCO‐entrapped mesoporous polydopamine nanoparticles are developed, which reach a 1.5 mg payload per gram carrier and exhibit marked theranostic capability through effective CO/Mn²⁺ generation and photothermal conversion inside the H⁺ and H₂O₂‐enriched tumor microenvironment, for a magnetic resonance/photoacoustic bimodal imaging‐guided tumor therapy. The multifunctional nanosystem exhibits a biocompatibility highly desirable for in vivo application and superior performance in inhibiting tumor growth and recurrence via combination CO and photothermal therapy.     

Biocompatible,Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo

Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.     

Optimization of Prussian Blue Coated NaDyF4:x%Lu Nanocomposites for Multifunctional Imaging‐Guided Photothermal Therapy

Imaging‐guided photothermal therapy based on functional nanomaterials has recently received significant attention and the selection of functional materials with optimal imaging and therapy effect is extremely important. In this work, NaDyF₄‐based nanoparticles with varying size are synthesized by doping with different amounts of lutetium ions. To obtain an optimized material, the influence factor of magnetic resonance, X‐ray attenuation, and photothermal properties are discussed in detail. Then, NaDyF₄:50%Lu@Prussian blue (PB) nanocomposite is selected as the optimal functional material for T₁‐ and T₂‐weighted magnetic resonance imaging, X‐ray computed tomography, and photothermal imaging‐guided photothermal therapy of tumor on a small animal model, and the treatment is applied with good results. Studies also suggest that the NaDyF₄:50%Lu@PB nanocomposites are biocompatibile. The selection of an optimal material from a multi‐perspective study has provided an incentive for the development of an assortment of novel multifunctional materials for early cancer multifunctional diagnosis and imaging‐guided photothermal therapy.     

Multifunctional Nanoparticle Loaded Injectable Thermoresponsive Hydrogel as NIR Controlled Release Platform for Local Photothermal Immunotherapy to Prevent Breast Cancer Postoperative Recurrence and Metastases

For breast cancer patients who have undergone breast‐conserving surgery, effective treatments to prevent local recurrences and metastases is very essential. Here, a local injectable therapeutic platform based on a thermosensitive PLEL hydrogel with near‐infrared (NIR)‐stimulated drug release is developed to achieve synergistic photothermal immunotherapy for prevention of breast cancer postoperative relapse. Self‐assembled multifunctional nanoparticles (RIC NPs) are composed of three therapeutic components including indocyanine green, a photothermal agent; resiquimod (R848), a TLR‐7/8 agonist; and CPG ODNs, a TLR‐9 agonist. RIC NPs are physically incorporated into the thermosensitive PLEL hydrogel. The RIC NPs encapsulated PLEL hydrogel (RIC NPs@PLEL) is then locally injected into the tumor resection cavity for local photothermal therapy to ablate residue tumor tissues and produce tumor‐associated antigens. At the same time, NIR also triggers the release of immune components CPG ODNs and R848 from thermoresponsive hydrogels PLEL. The released immune components, together with tumor‐associated antigens, work as an in situ cancer vaccine for postsurgical immunotherapy by inducing effective and sustained antitumor immune effect. Overall, this work suggests that photothermal immunotherapy based on local hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer to prevent recurrences and metastases.     

NIR Light‐Triggered Degradable MoTe2 Nanosheets for Combined Photothermal and Chemotherapy of Cancer

Telluride molybdenum (MoTe₂) nanosheets with wide near‐infrared (NIR) absorbance are functionalized with polyethylene glycol‐cyclic arginine‐glycine‐aspartic acid tripeptide (PEG‐cRGD). After loading a chemotherapeutic drug (doxorubicin, DOX), MoTe₂‐PEG‐cRGD/DOX is used for combined photothermal therapy and chemotherapy. With the high photothermal conversion efficiency, MoTe₂‐PEG‐cRGD/DOX exhibits favorable cells killing ability under NIR irradiation. Owing to the cRGD‐mediated specific tumor targeting, MoTe₂‐PEG‐cRGD/DOX shows efficient accumulation in tumors to induce a strong tumor ablation effect. MoTe₂‐PEG‐cRGD nanosheets, which are relatively stable in the circulation, could be degraded under NIR ray. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent, which could accumulate in tumors to allow photothermal imaging and combined therapy, is readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity, holding great potential to treat tumor effectively.