Binding to Amyloid-β Protein by Photothermal Blood-Brain Barrier-Penetrating Nanoparticles for Inhibition and Disaggregation of Fibrillation

Excess accumulation of amyloid-β (Aβ) protein in the brain is the primary pathogenesis of Alzheimer's disease (AD). Inhibition of Aβ fibrillation and disaggregation of Aβ fibrils is an attractive therapeutic and preventive strategy for Aβ-induced AD. Here, near infrared (NIR) light-responsive nanoparticles (NPs) composed of amphiphilic guanidinocalix[5]arene (GC5A), 4-(dodecyloxy)benzamido-terminated methoxy poly(ethylene glycol), and photothermal conjugated polymer PDPP are fabricated. The NIR light-responsive NPs can efficiently penetrate the blood-brain barrier (BBB), inhibit amyloid-β 42 (Aβ42) fibrillation, and disaggregate fibrils after NIR light irradiation. Through the advantage of containing GC5A, the NPs exhibit extremely strong binding affinity for the Aβ42 protein. Interestingly, upon NIR light irradiation, benefiting from the high photothermal conversion efficiency of PDPP, NPs generate local heat and effectively promote the BBB permeability. Moreover, NPs are multifunctional platforms for the inhibition of Aβ42 fibrillation and disaggregation of fibrils after irradiation with NIR light, distinctly reducing cytotoxicity and eliminating Aβ42 plaques in the hippocampus of AD mice. Hence, NPs provide an interesting strategy for the inhibition and disaggregation of Aβ42 fibrillation and present an excellent therapeutic strategy for amyloidosis.     

Gold Nanocage‐Based Dual Responsive “Caged Metal Chelator” Release System: Noninvasive Remote Control with Near Infrared for Potential Treatment of Alzheimer's Disease

Metal ions have been demonstrated to participate in the pathology of Alzheimer's disease (AD): amyloid‐β peptide (Aβ) aggregation and formation of neurotoxic reactive oxygen species (ROS), such as H₂O₂. Metal chelator can block ROS formation and inhibit metal induced Aβ aggregation. Metal‐ion chelation therapy as a compelling treatment for AD has been extensively studied. However, most chelators are not suitable for AD treatment because of their poor permeability of the blood–brain barrier and their limited ability to differentiate toxic metals associated with Aβ plaques from those associated with normal metal homeostasis. Here, a novel dual‐responsive “caged metal chelator” release system based on gold nanocage (AuNC) for AD treatment is reported. Since arylboronic ester is redox‐ and thermal‐sensitive, phenylboronic acid‐functionalized AuNC can serve as an efficient delivery system for H₂O₂‐responsive controlled release of metal chelator. The release can be further enhanced through remote control with NIR light because of the high near‐infrared absorbance of AuNC. The smart system can effectively inhibit Aβ aggregate formation, decrease cellular ROS, and protect cells from Aβ‐related toxicity. In light of these advantages, this design provides new insights into noninvasive remote control with NIR to improve therapeutic efficacy for treatment of Alzheimer's disease.     

Amyloid‐β Oligomer‐Targeted Gadolinium‐Based NIR/MR Dual‐Modal Theranostic Nanoprobe for Alzheimer's Disease

While the deposition of amyloid‐β (Aβ) plaques is one of the main pathological hallmarks of incurable Alzheimer's disease (AD), Aβ oligomers have been identified as a more appealing AD biomarker due to their being more pathogenic and neurotoxic. Therefore, the development of a sensitive and effective technique for oligomeric Aβ detection and imaging is beneficial for the early detection of AD, monitoring disease progression, and assessing the efficacy of potential AD drugs. Herein, the development and investigation of the first Aβ oligomer‐specific Gd³⁺‐based nanoparticles (NPs), NP@SiO₂@F‐SLOH as a multimodal near‐infrared imaging (NIRI)/T₁‐weighted magnetic resonance imaging (MRI) contrast agent for real‐time visualization of Aβ contents in an AD mouse model is reported. Remarkably, the NP@SiO₂@F‐SLOH is successfully applied for in vivo and ex vivo NIRI with high sensitivity and selectivity for Aβ oligomers and for MRI with good spatial resolution in different age groups in an AD mouse model. Furthermore, the NP probe exhibits a noticeable inhibitory effect on Aβ fibrillation and neuroprotection against Aβ‐induced toxicity indicating its desirable therapeutic potential for AD. All these results illustrate the tremendous potential of this versatile and sensitive nanomaterial as an effective theranostic MRI nanoprobe for practical use.     

Silica Nanodepletors: Targeting and Clearing Alzheimer's β‐Amyloid Plaques

Abnormal accumulation of β‐amyloid (Aβ) peptide aggregates in the brain is a major hallmark of Alzheimer's disease (AD). Aβ aggregates interfere with neuronal communications, ultimately causing neuronal damage and brain atrophy. Much effort has been made to develop AD treatments that suppress Aβ aggregate formation, thereby attenuating Aβ‐induced neurotoxicity. Here, the design of Aβ nanodepletors consisting of ultralarge mesoporous silica nanostructures and anti‐Aβ single‐chain variable fragments, with the goal of targeting and eliminating aggregative Aβ monomers, is reported. The Aβ nanodepletors impart a notable decline in Aβ aggregate formation, resulting in significant mitigation of Aβ‐induced neurotoxicity in vitro. Furthermore, stereotaxic injections of Aβ nanodepletors into the brain of an AD mouse model system successfully suppress Aβ plaque formation in vivo up to ≈30%, suggesting that Aβ nanodepletors can serve as a promising antiamylodoisis material.     

Tunable Förster Resonance Energy Transfer in Colloidal Nanoparticles Composed of Polycaprolactone‐Tethered Donors and Acceptors: Enhanced Near‐Infrared Emission and Compatibility for In Vitro and In Vivo Bioimaging

A near‐infrared (NIR) fluorescent donor/acceptor (D/A) nanoplatform based on Förster resonance energy transfer is important for applications such as deep‐tissue bioimaging and sensing. However, previously reported D/A nanoparticles (NPs) often show limitations such as aggregation‐induced fluorescence quenching and poor interfacial compatibility that reduces the efficiency of the energy transfer and also leads to leaching of the small molecular fluorophores from the NP matrix. Here highly NIR‐fluorescent D/A NPs with a fluorescence quantum yield as high as 46% in the NIR region (700–850 nm) and robust optical stability are reported. The hydrophobic core of each NP is composed of donor and acceptor moieties both of which are tethered with polycaprolactone (PCL), while the hydrophilic corona is composed of poly[oligo(ethylene glycol) methyl ether methacrylate] to offer colloidal stability and “stealthy” effect in aqueous media. The PCL matrix in each colloidal NP not only offers biocompatibility and biodegradability but also minimizes the aggregation‐caused fluorescence quenching of D/A chromophores and prevents the leakage of the NIR fluorophores from the NPs. In vivo imaging using these NIR NPs in live mice shows contrast‐enhanced imaging capability and efficient tumor‐targeting through enhanced permeability and retention effect.     

pH‐Responsive Cyanine‐Grafted Graphene Oxide for Fluorescence Resonance Energy Transfer‐Enhanced Photothermal Therapy

Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.     

Biocompatible D–A Semiconducting Polymer Nanoparticle with Light‐Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy

The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor–acceptor conjugated semiconducting polymer nanoparticles (PPor‐PEG NPs) with light‐harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light‐harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer‐based theranostic agent. Combined with additional merits including donor–acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor‐PEG NPs is determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as‐prepared PPor‐PEG NP not only exhibits a remarkable cell‐killing ability but also achieves 100% tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as‐prepared water‐dispersible PPor‐PEG NPs show good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.     

Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (¹O₂) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.     

SnTe@MnO2‐SP Nanosheet–Based Intelligent Nanoplatform for Second Near‐Infrared Light–Mediated Cancer Theranostics

Near infrared light, especially the second near‐infrared light (NIR II) biowindows with deep penetration and high sensitivity are widely used for optical diagnosis and phototherapy. Here, a novel kind of 2D SnTe@MnO₂‐SP nanosheet (NS)‐based nanoplatform is developed for cancer theranostics with NIR II‐mediated precise optical imaging and effective photothermal ablation of mouse xenografted tumors. The 2D SnTe@MnO₂‐SP NSs are fabricated via a facile method combining ball‐milling and liquid exfoliation for synthesis of SnTe NSs, and surface coating MnO₂ shell and soybean phospholipid (SP). The ultrathin SnTe@MnO₂‐SP NSs reveal notably high photothermal conversion efficiency (38.2% in NIR I and 43.9% in NIR II). The SnTe@MnO₂‐SP NSs inherently feature tumor microenvironment (TME)‐responsive biodegradability, and the main metabolite TeO₃^2? shows great antitumor effect, coupling synergetic chemotherapy for cancer. Moreover, the SnTe@MnO₂‐SP NSs also exhibit great potential for fluorescence, photoacoustic (PA), and photothermal imaging agents in the NIR II biowindow with much higher resolution and sensitivity. This is the first report, as far as is known, with such an inorganic nanoagent setting fluorescence/PA/photothermal imaging and photothermal therapy in NIR II biowindow and TME‐responsive biodegradability rolled into one, which provide insight into the clinical potential for cancer theranostics.     

Manipulating the Motion of Gold Aggregates Using Stimulus‐Responsive Patterned Polymer Brushes as a Motor

An important goal and major challenge of material science and nanotechnology is building nanomotors for manipulating the motion of nanoparticles (NPs). Here, it is demonstrated that patterned, stimulus‐responsive polymer brush microstructures can be used as motor arrays to manipulate the movement of gold NP aggregates in response to external stimuli that induce a conformational change in the brushes as the driving force. The motion of NP aggregates in the out‐of‐plane direction is achieved with displacements ranging from nanometers to sub‐micrometers. These patterned polymer‐brush microstructures can find applications as efficient motor arrays and nanosensors, and benefit the design of more complex nanodevices.     

Remotely Controlled Red Blood Cell Carriers for Cancer Targeting and Near‐Infrared Light‐Triggered Drug Release in Combined Photothermal–Chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus‐responsive, RBC‐based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near‐infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light‐induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC‐based cancer cell targeted drug delivery and light‐controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.     

Two‐Stage Size Decrease and Enhanced Photoacoustic Performance of Stimuli‐Responsive Polymer‐Gold Nanorod Assembly for Increased Tumor Penetration

A promising theranostic platform for solid tumors would deliver and release anticancer nanomedicine effectively in tumor cells. However, diverse biological barriers, especially related to the tumor microenvironment, impede these theranostic agents from reaching the tumor cell. Herein, a sequential pH and reduction‐responsive polymer and gold nanorod (AuNR) core–shell assembly to overcome these barriers via a two‐stage size decrease and disassembly of the nanoplatform responding to the specified tumor microenvironment are reported. The tumor uptake of the hybrid nanoparticle (NP) is 14.2% ID g^?1, which is two and four times higher than the noneresponsive hybrid NPs and small AuNR@PEG, respectively. After tumor uptake of the hybrid NPs, the disassembled ultrasmall AuNRs coated with a polymer of polymerized reduction‐responsive doxorubicin (DOX) prodrug monomers penetrate into the solid tumor and lead to localized DOX release in the tumor cell. A linear increase in photoacustic (PA) effects from the PA activating polymer on an AuNR cluster surface indicates a critical role of electromagnetic fields in the AuNR assembly, which is consistent with the theoretical calculation results. Furthermore, the hybrid NP can serve as a promising deep‐tissue PA and surface‐enhanced Raman scattering imaging agent for real‐time in vivo investigation of physiological behaviors and deep tumor penetrating nanotherapy effects.     

Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ～10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.     

Bioinspired Nanoparticles with NIR‐Controlled Drug Release for Synergetic Chemophotothermal Therapy of Metastatic Breast Cancer

Optimal nanosized drug delivery systems (NDDS) require long blood circulation and controlled drug release at target lesions for efficient anticancer therapy. Red blood cell (RBC) membrane‐camouflaged nanoparticles (NPs) can integrate flexibility of synergetic materials and highly functionality of RBC membrane, endowed with many unique advantages for drug delivery. Here, new near‐infrared (NIR)‐responsive RBC membrane‐mimetic NPs with NIR‐activated cellular uptake and controlled drug release for treating metastatic breast cancer are reported. An NIR dye is inserted in RBC membrane shells, and the thermoresponsive lipid is employed to the paclitaxel (PTX)‐loaded polymeric cores to fabricate the RBC‐inspired NPs. The fluorescence of dye in the NPs can be used for in vivo tumor imaging with an elongated circulating halftime that is 12.3‐folder higher than that of the free dye. Under the NIR laser stimuli, the tumor cellular uptake of NPs is significantly enhanced to 2.1‐fold higher than that without irradiation. The structure of the RBC‐mimetic NPs can be destroyed by the light‐induced hyperthermia, triggered rapid PTX release (45% in 30 min). These RBC‐mimetic NPs provide a synergetic chemophotothermal therapy, completely inhibited the growth of the primary tumor, and suppress over 98% of lung metastasis in vivo, suggesting it to be an ideal NDDS to fight against metastatic breast cancer.     

Fluorescence Quenching upon Binding of Copper Ions in Dye‐Doped and Ligand‐Capped Polymer Nanoparticles: A Simple Way to Probe the Dye Accessibility in Nano‐Sized Templates

The synthesis and properties of well‐defined core–shell type fluorescent metal‐chelating polymer nanoparticles NP, in the 15 nm diameter range, with a fluorophore (9,10‐diphenylanthracene: DPA) entrapped in the particle core and a selective ligand (1,4,8,11‐tetraazacyclotetradecane: Cyclam), grafted onto the surface are presented. NPs with different number of dye‐per‐particle are readily obtained by entrapment of the fluorophore within the polymer core. The ligand‐coated NPs exhibit a high affinity for Cu²⁺ ions in aqueous solution and quenching of the DPA fluorescence is observed upon binding of copper. The quenching of fluorescence arises through energy transfer (FRET) from the dye to the copper‐cyclam complexes that form at the NP surface with an operating distance (d) in the 2 nm range. A simple core–shell model accounts for the steady‐state and time‐resolved fluorescence titration experiments: dye molecules located in the outer sphere (thickness d) of the NPs are quenched while the fluorescence of dyes embedded more deeply is not affected by the binding of copper ions. The observed high quenching efficiency (60–65 %), which is tightly correlated to the volumic and microstructural features of the NPs, shed light on the enhanced accessibility inherent in nano‐sized templates. The response towards different metal ions was investigated and this confirmed the selectivity of the nanoparticle template‐assembled sensor for cupric ions.     

pH‐ and NIR Light‐Responsive Micelles with Hyperthermia‐Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer

The acquisition of multidrug resistance (MDR) is a major hurdle for the successful chemotherapy of tumors. Herein, a novel hybrid micelle with pH and near‐infrared (NIR) light dual‐responsive property is reported for reversing doxorubicin (DOX) resistance in breast cancer. The hybrid micelles are designed to integrate the pH‐ and NIR light‐responsive property of an amphiphilic diblock polymer and the high DOX loading capacity of a polymeric prodrug into one single nanocomposite. At physiological condition (i.e., pH 7.4), the micelles form compact nanostructure with particle size around 30 nm to facilitate blood circulation and passive tumor targeting. Meanwhile, the micelles are quickly dissociated in weakly acidic environment (i.e., pH ≤ 6.2) to release DOX prodrug. When exposed to NIR laser irradiation, the hybrid micelles can trigger notable tumor penetration and cytosol release of DOX payload by inducing tunable hyperthermia effect. In combination with localized NIR laser irradiation, the hybrid micelles significantly inhibit the growth of DOX‐resistant MCF‐7/ADR breast cancer in an orthotopic tumor bearing mouse model. Taken together, this pH and NIR light‐responsive micelles with hyperthermia‐triggered tumor penetration and cytoplasm drug release can be an effective nanoplatform to combat cancer MDR.     

Thermoresponsive Nanogel‐Encapsulated PEDOT and HSP70 Inhibitor for Improving the Depth of the Photothermal Therapeutic Effect

Photothermal therapy (PTT), a new, noninvasive treatment measure, has recently drawn much attention. However, due to the limited penetration depth of near‐infrared (NIR) light, PTT is focused on treating superficial tumors. Improving the depth of the therapeutic effect is a bottleneck for successful PTT. To solve this problem, a new kind of nanoplatform (Nanogel+phenylethynesulfonamide (PES)) is fabricated by using a thermo‐responsive polymer shell (poly(N‐isopropylacrylamide‐co‐acrylic acid) to encapsulate 2‐PES, an effective heat shock protein 70 (HSP70) inhibitor, and poly(3,4‐ethylenedioxythiophene), a widely used photothermal coupling agent. Upon NIR irradiation, PES can be released from the Nanogel+PES when a thermo‐responsive phase transition occurs, which could restrain the function of HSP70 and reduces the cells' endurance to heat. In this way, a better therapeutic effect on deeper tissues is achieved with a relatively small rise in temperature. Therefore, with the advantages of the thermo‐responsive photothermal effect, coupled with the inhibition of HSP70, and minimal cytotoxicity, the Nanogel+PES appears to be a promising photothermal agent that can improve the depth of the PTT effect.     

Human HSP70 Promoter‐Based Prussian Blue Nanotheranostics for Thermo‐Controlled Gene Therapy and Synergistic Photothermal Ablation

Realizing precise control of the therapeutic process is crucial for maximizing efficacy and minimizing side effects, especially for strategies involving gene therapy (GT). Herein, a multifunctional Prussian blue (PB) nanotheranostic platform is first designed and then loaded with therapeutic plasmid DNA (HSP70‐p53‐GFP) for near‐infrared (NIR) light‐triggered thermo‐controlled synergistic GT/photothermal therapy (PTT). Due to the unique structure of the PB nanocubes, the resulting PB@PEI/HSP70‐p53‐GFP nanoparticles (NPs) exhibit excellent photothermal properties and pronounced tumor‐contrast performance in T₁/T₂‐weighted magnetic resonance imaging. Both in vitro and in vivo studies demonstrate that mild NIR‐laser irradiation (≈41 °C) activates the HSP70 promoter for tumor suppressor p53‐dependent apoptosis, while strong NIR‐laser irradiation (≈50 °C) induces photothermal ablation for cellular dysregulation and necrosis. Significant synergistic efficacy can be achieved by adjusting the NIR‐laser irradiation (from ≈41 to ≈50 °C), compared to using GT or PTT alone. In addition, in vitro and in vivo toxicity studies demonstrate that PB@PEI/HSP70‐p53‐GFP NPs have good biocompatibility. Therefore, this work provides a promising theranostic approach for controlling combined GT and PTT via the heat‐shock response.     

Stimuli‐Responsive Scaffold for Breast Cancer Treatment Combining Accurate Photothermal Therapy and Adipose Tissue Regeneration

Development of new therapeutic scaffolds to selectively destruct tumors under gentle conditions meanwhile promoting adipose tissue formation would be a promising strategy for clinical treatment of breast cancer. Herein, a stimuli‐responsive scaffold composed of polyacrylic acid‐g‐polylactic acid (PAA‐g‐PLLA) modified graphene oxide (GO) with a cleavable bond in between (GO‐PAA‐g‐PLLA), gambogic acid (GA), and polycaprolactone (PCL) is fabricated and then preseeded on adipose‐derived stem cells (ADSCs) for breast cancer treatment. This GO–GA‐polymer scaffold is able to simultaneously perform pH‐triggered low temperature (45 °C) photothermal therapy to selectively induce the apoptosis of tumor cells and significantly improve ADSCs growth without any photothermal damage. The low‐temperature photothermal therapy of the scaffolds can induce more than 95% of cell death for human breast cancer (MCF‐7) in vitro, which further completely inhibits tumor growth and finally eliminates tumor tissue in mice. Meanwhile, the prepared GO–GA‐polymer scaffold possesses the improved capability to stimulate the differentiation of ADSCs into adipocytes by upregulating adipo‐related gene expression, and significantly promotes new adipose tissue formation whether with or without NIR irradiation. These results successfully demonstrate that the prepared GO–GA‐polymer scaffolds with bifunctional properties will be a promising candidate for clinical cases involving both tumor treatment and tissue engineering.     

NIR‐Triggered Synergic Photo‐chemothermal Therapy Delivered by Reduced Graphene Oxide/Carbon/Mesoporous Silica Nanocookies

A novel photo‐responsive drug carrier that doubles as a photothermal agent with a nanocookie‐like structure is constructed by coating amorphous carbon on a mesoporous silica support self‐assembled on a sheet of reduced graphene oxide. With a large payload (0.88 mmolg^?1) of a hydrophobic anticancer drug, (S)‐(+)‐camptothecin (CPT), nanocookies simultaneously provide a burst‐like drug release and intense heat upon near‐infrared exposure. Being biocompatible yet with a high efficiency for cell uptake, nanocookies have successfully eradicated subcutaneous tumors in 14 days following a single 5 min NIR irradiation without distal damage. These results demonstrate that the nanocookie is an excellent new delivery platform for local, on‐demand, NIR‐responsive, combined chemotherapy/hyperthermia for tumor treatment and other biomedical applications.