Biomimetic Nanocomposites for Glioma Imaging and Therapy.

Glioma, the most common primary brain tumor, is highly invasive and grows rapidly. As such, the survival of glioma patients is relatively short, highlighting the vital importance of timely diagnosis and treatment of glioma. However, the blood brain barrier (BBB) and the non-targeting delivery systems of contrast agents and drugs greatly hinder the effective glioma imaging and therapy. Fortunately, in recent years, investigators have constructed various biomimetic delivery platforms utilizing the exceptional advantages of biomimetic nanocomposites, such as immune evasion, homologous targeting ability, and BBB penetrating ability, to achieve efficient and precise delivery of substances to glioma sites for improved diagnosis and treatment. In this concept, we present the application of these biomimetic nanocomposites in fluorescence imaging (FI), magnetic resonance imaging (MRI), and multi-modal imaging, as well as in chemotherapy, phototherapy, and combined therapy for glioma. Lastly, we provide our perspective on this research field.

TiO2-Ti3C2 Nanocomposites Utilize Their Photothermal Activity for Targeted Treatment of Colorectal Cancer.

Purpose: The search for effective and low-risk treatment methods for colorectal cancer (CRC) is a pressing concern, given the inherent risks and adverse reactions associated with traditional therapies. Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment, offering advantages such as non-radiation, non-invasiveness, and targeted treatment. Consequently, the development of nanoparticles with high stability, biocompatibility, and photothermal effects has become a significant research focus within the field of PTT. Methods: In this study, TiO2-Ti3C2 nanocomposites were synthesized and characterized, and their photothermal conversion efficiency in the near-infrared region II (NIR-II) was determined. Then studied the in vivo and in vitro photothermal activity and anti-tumor effect of TiO2-Ti3C2 in human colorectal cancer cell lines and nude mice subcutaneous tumor model. Results: The results showed that TiO2-Ti3C2 nanocomposites have strong absorption ability in the NIR-II, and have high photothermal conversion efficiency under 1064 nm (0.5 W/cm2, 6 min) laser stimulation. In addition, in vitro experiments showed that TiO2-Ti3C2 nanocomposites significantly inhibited the invasion, migration, and proliferation of colorectal cancer cells, and induced cell apoptosis; in vivo, experiments showed that TiO2-Ti3C2 nanocomposites-mediated PTT had good biocompatibility and efficient targeted inhibition of tumor growth. Conclusion: In conclusion, TiO2-Ti3C2 nanocomposites can be used as NIR-II absorption materials in PTT to suppress the invasion, migration, and proliferation of colorectal cancer cells, induce colorectal cancer cell apoptosis, and thus inhibit the development of CRC. Therefore, TiO2-Ti3C2 nanocomposites can be used as potential anti-tumor drugs for photothermal ablation of colorectal cancer cells.

Biomedical application of metal-organic frameworks (MOFs) in cancer therapy: Stimuli-responsive and biomimetic nanocomposites in targeted delivery, phototherapy and diagnosis.

The nanotechnology is an interdisciplinary field that has become a hot topic in cancer therapy. Metal-organic frameworks (MOFs) are porous materials and hybrid composites consisted of organic linkers and metal cations. Despite the wide application of MOFs in other fields, the potential of MOFs for purpose of cancer therapy has been revealed by the recent studies. High surface area and porosity, significant drug loading and encapsulation efficiency are among the benefits of using MOFs in drug delivery. MOFs can deliver genes/drugs with selective targeting of tumor cells that can be achieved through functionalization with ligands. The photosensitizers and photo-responsive nanostructures including carbon dots and gold nanoparticles can be loaded in/on MOFs to cause phototherapy-mediated tumor ablation. The immunogenic cell death induction and increased infiltration of cytotoxic CD8+ and CD4+ T cells can be accelerated by MOF platforms in providing immunotherapy of tumor cells. The stimuli-responsive MOF platforms responsive to pH, redox, enzyme and ion can accelerate release of therapeutics in tumor site. Moreover, MOF nanocomposites can be modified ligands and green polymers to improve their selectivity and biocompatibility for cancer therapy. The application of MOFs for the detection of cancer-related biomarkers can participate in the early diagnosis of patients.

Hollow Cavity CaO2 @Polydopamine Nanocomposites for pH-Responsive Ca2+ -Enhanced Efficient Mild Hyperthermia in the NIR-II Region.

Second near-infrared (NIR-II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR-II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR-II region is improved by developing novel hollow cavity CaO2 @PDA nanocomposites through chelation-induced diffusion of inner core Ca2+ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH-responsive degradation of CaO2 , its structure is transformed into a stacked "nano-mesh" with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca2+ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR-II region.

Gold-Crowned Bismuth-Based Nanocomposites for Sonodynamic, Photothermal, and Chemotherapeutic Cancer Therapy.

Conventional inorganic semiconductor nanoparticles have emerged as photothermal agents in photothermal therapy and as sonosensitizers in sonodynamic therapy. However, their weak drug-loading capabilities and the deficient techniques for multifunctional inorganic nanoparticles limit their applications. A bismuth-based gold-crowned nanocomposite (BACN) was rationally designed and successfully synthesized and could then be used to prepare nanoplatforms with excellent biocompatibilities for synergistic therapy and real-time imaging. Because of the constituent gold nanoparticles and pyridine, the nanoplatforms functioned as drug delivery vehicles, ultrasonically activated sonosensitizers, and photothermal agents. The BACNs exhibited excellent photothermal conversion efficiency (79.1%) in the second near-infrared biowindow (1064 nm). Cellular and mouse experiments demonstrated that under laser and ultrasound irradiation bufalin-loaded BACNs significantly reduced cancer cell counts and completely eradicated tumors, along with great therapeutic biosafety and no discernible recurrence. Additionally, BACNs were also used as contrast agents in computed tomography-photoacoustic imaging. The versatile BACN nanoplatform with multitreatment effects and trimodal imaging properties shows immense potential as an antitumor nanotherapeutic system.

Imaging-Guided Photoacoustic Immunotherapy Based on the Polydopamine-Functionalized Black Phosphorus Nanocomposites.

Phototherapy has great application prospects in superficial tumors, such as melanoma, esophageal cancer, and breast carcinoma, owing to the advantages of noninvasiveness, high spatiotemporal selectivity, and less side effects. However, classical phototherapies including photodynamic and photothermal therapy still need to settle the bottleneck problems of poor efficacy, inevitable thermal damage, and a high rate of postoperative recurrence. In this study, we developed a nanocomposite with excellent optical properties and immune-stimulating properties, termed PBP@CpG, which was obtained by functionalizing black phosphorus (BP) with polydopamine and further adsorbing CpG. Benefiting from the protection of polydopamine against BP, ideal light absorption, and photoacoustic conversion properties, PBP@CpG not only enables precisely delineation of the tumor region with photoacoustic imaging but also powerfully disrupts the plasma membrane and cytoskeleton of tumor cells with a photoacoustic cavitation effect. In addition, we found that the photoacoustic cavitation effect was also capable of inducing immunogenic cell death and remarkably strengthening the antitumor immune response upon cooperating with immune adjuvant CpG. Therefore, PBP@CpG was expected to provide a promising nanoplatform for optical theranostics and herald a new strategy of photoimmunotherapy based on the photoacoustic cavitation effects and immunostimulatory effect.

Injectable biocompatible nanocomposites of Prussian blue nanoparticles and bacterial cellulose as a safe and effective photothermal cancer therapy.

Photothermal therapy (PTT) is a novel cancer treatment using a photoabsorber to cause hyperthermia to kill tumors by laser irradiation. Prussian blue nanoparticles (PB NPs) are considered as next-generation photothermal agents due to the facile synthesis and excellent absorption of near-infrared light. Although PB NPs demonstrate remarkable PTT capabilities, their clinical application is limited due to their systemic toxicity. Bacterial cellulose (BC) has been applied to various bio-applications based on its unique properties and biocompatibility. Herein, we design composites with PB NPs and BC as an injectable, highly biocompatible PTT agent (IBC-PB composites). Injectable bacterial cellulose (IBC) is produced through the trituration of BC, with PB NPs synthesized on the IBC surface to prepare IBC-PB composites. IBC-PB composites show in vitro and in vivo photothermal therapeutic effects similar to those of PB NPs but with significantly greater biocompatibility. Specifically, in vitro therapeutic index of IBC-PB composites is 26.5-fold higher than that of PB NPs. Furthermore, unlike PB NPs, IBC-PB composites exhibit no overt toxicity in mice as assessed by blood biochemical analysis and histological images. Hence, it is worth pursuing further research and development of IBC-PB composites as they hold promise as safe and efficacious PTT agents for clinical application.

Multi-Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi-Tumor Cases.

Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects.

Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel "all-in-one" chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.

Target Embolization Combined with Multimodal Thermal Ablation for Solid Tumors by Smart Poly(amino acid)s Nanocomposites.

Noninterventional embolization does not require the use of a catheter, and the treatment of solid tumors in combination with thermal ablation can avoid some of the risks of the surgical procedure. Therefore, we developed an efficient tumor microenvironment-gelled nanocomposites with poly [(l-glutamic acid-ran-l-tyrosine)-b-l-serine-b-l-cysteine] (PGTSCs) coated-nanoparticles (Fe3O4&Au@PGTSCs), from which the prepared PGTSCs were given possession of pH response to an acidic tumor microenvironment. Fe3O4&Au@PGTSC in noninterventional embolization treatment not only achieved the smart targeted medicine delivery but also meshed with noninvasive multimodal thermal ablation therapy and multimodal imaging of solid tumors via intravenous injection. It was worth noting that the results of animal experiments in vivo demonstrated that Fe3O4&Au@PGTSCs have specific tumor accumulation and embolization and thermal ablation effects; at 10 days postinjection, only scars were found at the tumor site. After 20 days, the tumors of model mice completely disappeared. This device is easier to treat solid tumors based on the slightly acidic tumor environment.

A Gas/phototheranostic Nanocomposite Integrates NIR-II-Peak Absorbing Aza-BODIPY with Thermal-Sensitive Nitric Oxide Donor for Atraumatic Osteosarcoma Therapy.

Photothermal therapy (PTT) has received increasing interest in cancer therapeutics owing to its excellent efficacy and controllability. However, there are two major limitations in PTT applications, which are the tissue penetration depth of lasers within the absorption range of photothermal agents and the unavoidable tissue empyrosis induced by high-energy lasers. Herein, a gas/phototheranostic nanocomposite (NA1020-NO@PLX) is engineered that integrates the second near-infrared-peak (NIR-II-peak) absorbing aza-boron-dipyrromethenes (aza-BODIPY,NA1020) with the thermal-sensitive nitric oxide (NO) donor (S-nitroso-N-acetylpenicillamine, SNAP). An enhanced intramolecular charge transfer mechanism is proposed to achieve the NIR-II-peak absorbance (λmax = 1020 nm) on NA1020, thereby obtaining its deep tissue penetration depth. The NA1020 exhibits a remarkable photothermal conversion, making it feasible for the deep-tissue orthotopic osteosarcoma therapy and providing favorable NIR-II emission to precisely pinpoint the tumor for a visible PTT process. The simultaneously investigated atraumatic therapeutic process with an enhanced cell apoptosis mechanism indicates the feasibility of the synergistic NO/low-temperature PTT for osteosarcoma. Herein, this gas/phototheranostic strategy optimizes the existing PTT to present a repeatable and atraumatic photothermal therapeutic process for deep-tissue tumors, validating its potential clinical applications.

Multifunctional manganese oxide-based nanocomposite theranostic agent with glucose/light-responsive singlet oxygen generation and dual-modal imaging for cancer treatment.

Development of tumor microenvironment (TME) modifying nanomedicine with cooperative effect between multiple stimuli responsive therapeutic modalities is necessary to achieve lower dosage induced tumor specific therapy. Accordingly, herein, a multifunctional MnOx NSs@BSA-IR780-GOx nanocomposite (MBIG NCs) is developed to modulate the oxidative stress in TME, and thus attain higher therapeutic efficacy. In the presence of glucose, the as-synthesized MBIG NCs are served as a chemodynamic agents and generated reactive oxygen species (ROS) by self-activation through a cascade of reactions from glucose oxidase (GOx) and manganese oxide nanosheets (MnOx NSs). Also, the MBIG NCs demonstrated excellent photodynamic properties upon irradiation with 808 nm laser owing to the presence of IR780. The combination of glucose-mediated chemodynamic and light-mediated photodynamic properties generated higher ROS than that obtained with individual stimuli. Further, the MBIG NCs exhibited photothermal effect with conversion efficiency of 33.8 %, which helped to enhance the enzymatic activities. In in vitro studies, the MBIG NCs exhibited good biocompatibility to cancerous and non-cancerous cells under non-stimulus conditions. Nevertheless, in the presence of glucose and light stimuli, they triggered more than 90 % cell toxicity at 200 ppm concentration via the cooperative effect between starvation therapy, chemodynamic therapy, and phototherapy. Furthermore, the MBIG NCs demonstrated magnetic resonance and fluorescence imaging properties. These results are suggesting that MBIG NCs would be potential theranostic agents to for cancer diagnosis and target specific therapy. More importantly, the fabrication process is paving a way to improve the aqueous dispersibility, stability, and bio-applicability of MnOx NSs and IR780.

Tyrosinase-activated Nanocomposites for Double-Modals Imaging Guided Photodynamic and Photothermal Synergistic Therapy.

Tyrosinase (TYR) is an important biomarker of melanoma. The exploration of fluorescent pr-obes-based composites is beneficial to build an integrative platform for the diagnosis and treatment of melanoma. Herein, a multifunctional nanocomposite IOBOH@BSA activated by TYR is developed for selective imaging and ablation of melanoma. The chemical structure of IOBOH enables the fluorescence (FL) imaging activated by TYR, photoacoustic (PA) imaging, and photodynamic-photothermal activity by regulating the balance between radiative decay and non-radiative decay. IOBOH combined with bovine serum albumin (IOBOH@BSA) presents the response to TYR and realizes FL imaging with mitochondria-targeting in melanoma. Moreover, IOBOH@BSA shows excellent photothermal ability and is applied for PA imaging. After IOBOH@BSA is activated by TYR, the singlet oxygen generation increases obviously. IOBOH@BSA can realize TYR-activated imaging and photodynamic-photothermal therapy of melanoma. The development of TYR-activated multifunctional nanocomposites promotes the precise imaging and improves the therapeutic effect of melanoma.

Inhibition of Pro-Survival Autophagy Induced by Rare-Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors.

Manipulation of autophagic processes has emerged as a promising strategy for synergizing nanoagent-mediated photothermal therapy (PTT). Most of the current studies focus on improving PTT efficacy by inhibiting pro-survival autophagy induced by the heat generated from the photothermal process. However, autophagy induced by the nanoagents is usually ignored, which may weaken the effect of autophagy-mediated efficacy improvement in PTT if induced autophagy is pro-death. Therefore, this work aims at developing a nanoagent that is able to induce heat-synergetic pro-survival autophagy to optimize the efficacy of PTT. An approach is developed to coat carbon layer, polyethylenimine (PEI), and folic acid (FA) on NaYF4 :Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA, DCPF) nanoparticles successively, giving access to the nanoagent to induce pro-survival autophagy. The synthetic imaging-guided photothermal nanoagent displays outstanding targeting ability and biocompatibility based on the surface modification of PEI and FA. By using an autophagy inhibitor chloroquine, a conspicuously synergistic effect on DCPF-mediated PTT in vitro and in vivo tumor models (HeLa) is achieved. A promising strategy is presented here to enhance the efficacy of imaging-guided PTT by modulating the autophagy induced by the nanoagent.

Multifunctional Au Modified Ti3C2-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy.

Ti3C2-MXene-based composites provide multifunctional interfaces in diagnosis and treatment of tumors. Herein, we proposed a multifunctional nanoplatform based on Ti3C2-MXene-Au nanocomposites, which combines photothermal properties and peroxidase-like activity, accomplishing synergistic photothermal therapy (PTT) and enzyme dynamic therapy (EDT) accompanied by photoacoustic (PA) and thermal dual-mode imaging in vivo. Furthermore, PTT induces immunogenic cell death, and EDT promotes cell apoptosis, facilitating dendritic cell (DC) maturation and T cell infiltration into the tumor. On this basis, the antibody OX40 (αOX40) was utilized to further contribute immune therapy for reversing the immunosuppressive tumor microenvironment by activating CD4+ and CD8+ T cells. In summary, a triune of PTT/EDT/antitumor immune therapy is achieved by combining Ti3C2-MXene-Au nanocomposites and αOX40, which possesses several strong features of good biocompatibility, NIR-controlled targeting, significant cancer cell killing, and satisfactory biosafety in vitro and in vivo. Our work might highlight the promising application of MXene-based nanoplatforms for cancer therapy.

Fabrication of a magnetic alginate-silk fibroin hydrogel, containing halloysite nanotubes as a novel nanocomposite for biological and hyperthermia applications.

In this study, the main focus was on designing and synthesizing a novel magnetic nanobiocomposite and its application in hyperthermia cancer treatment. Regarding this aim, sodium alginate (SA) hydrogel with CaCl2 cross-linker formed and modified by silk fibroin (SF) natural polymer and halloysite nanotubes (HNTs), followed by in situ Fe3O4 magnetic nanoparticles preparation. No important differences were detected in red blood cells (RBCs) hemolysis, confirming the high blood compatibility of the treated erythrocytes with this nanobiocomposite. Moreover, the synthesized SA hydrogel/SF/HNTs/Fe3O4 nanobiocomposite does not demonstrate toxicity toward HEK293T normal cell line after 48 and 72 h. The anticancer property of SA hydrogel/SF/HNTs/Fe3O4 nanobiocomposites against breast cancer cell lines was corroborated. The magnetic saturation of the mentioned magnetic nanobiocomposite was 15.96 emu g-1. The specific absorption rate (SAR) was measured to be 22.3 W g-1 by applying an alternating magnetic field (AMF). This novel nanobiocomposite could perform efficiently in the magnetic fluid hyperthermia process, according to the obtained results.

Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.

Rod-like hybrid nanomaterial with tumor targeting and pH-responsive for cancer chemo/photothermal synergistic therapy.

The development of chemo/photothermal nanotherapeutic systems with excellent photothermal performance, stable drug loading, tumor targeting and strong membrane penetration still remains a challenge. To address this problem, herein a rod-like nanocomposite system (AuNR@FA-PR/PEG) forming from folic acid (FA) terminated carboxylated cyclodextrin (CD) pseudopolyrotaxane (FA-PR) and polyethylene glycol (PEG) modifying gold nanorods (AuNR) was reported. Cisplatin (CDDP) was loaded in AuNR@FA-PR/PEG via coordination bonds to prepare a rod-like pH-responsive nanosystem (AuNR@FA-PR/PEG/CDDP) with chemotherapy/photothermal therapy. The rod-like morphology of AuNR@FA-PR/PEG was characterized by transmission electron microscope. In vitro drug release experiments showed the pH-responsive of AuNR@FA-PR/PEG/CDDP. In vivo real-time imaging assays proved AuNR@FA-PR/PEG/CDDP could rapidly enrich in the tumor area and stay for a long time because of folate targeting and their rod-like morphology. In vivo photothermal imaging assays showed AuNR@FA-PR/PEG/CDDP excellent photothermal performance, the average temperature of tumor region could reach 63.5 °C after 10 min irradiation. In vitro and in vivo experiments also demonstrated that the combined therapy of chemotherapy and photothermal therapy had an outstandingly synergistic effect and improved the therapeutic efficacy comparing with chemotherapy and photothermal therapy alone. Therefore, the prepared rod-like AuNR@FA-PR/PEG/CDDP will provide a new strategy for the effective treatment of cancer.

CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy.

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of H2O2 to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm-2, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of H2O2, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (1O2). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.