Multifunctional Theranostic Nanoplatform Research Articles

Advancing immunotherapy in triple negative breast Cancer: A novel multimodal theranostic nanoplatform integrating synergetic ferroptosis and photothermal therapy

Triple negative breast cancer (TNBC) is a subtype of breast cancer with high invasiveness and the worst prognosis. Immunotherapy has demonstrated significant potential in its treatment. However, the response rate remains unsatisfactory. In this work, we prepared multifunctional theranostic nanoplatforms (P-R@P/U-V) with synergetic ferroptosis and photothermal therapy (PTT) in improving TNBC tumor microenvironment for improving local treatment in situ, and synergistic anti-programmed cell death-ligand 1 (PD-L1) immunotherapy to prevent distant metastasis. With P-R@P/U-V, real-time monitoring of the specific distribution in tumors is possible due to the greatly improved ultrasound imaging (US), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capabilities. Moreover, P-R@P/U-V has excellent photothermal conversion ability. Whereas PTT killed TNBC cells after laser irradiation, the liquid–gas phase transition not only improved US but also triggered controllable release of RSL3 in situ, enhancing ferroptosis of TNBC cells. Besides, the release of tumor-associated antigens (TAAs) increased via PTT and ferroptosis, strongly stimulating T cell activation, dendritic cell maturation, and anti-tumor cytokine secretion. The lung metastases of TNBC were significantly inhibited following the combined use of P-R@P/U-V and PD-L1 inhibitors. The multimodal and multifunctional nanoplatforms demonstrated excellent effects in early diagnosis and synergistic treatment of TNBC. This represents a novel strategy based on local treatment for additional enhanced anti-PD-L1 immunotherapy, with high clinical application prospects.

Intelligent responsive copper-diethyldithiocarbamate-based multifunctional nanomedicine for photothermal-augmented synergistic cancer therapy.

The design of multifunctional nanomedicine through the combination of multimodal treatments to achieve the optimal antitumor effect is essential for cancer therapy. Herein, we design and develop a multifunctional theranostic nanoplatform using an iron ion-doxorubicin (DOX) nanoscale coordination polymer (Fe/DOX NCP) as a shell coating on the surface of polyvinyl pyrrolidone (PVP) stabilized copper-diethyldithiocarbamate nanoparticles (Cu(DDC)2 NPs) for combined tumor chemo-/photothermal/chemodynamic therapy. The obtained Cu(DDC)2@Fe/DOX NPs display pH/laser dual-responsive degradation behavior and also exhibit favorable photothermal performance. Under 808 nm laser irradiation, Cu(DDC)2@Fe/DOX NPs can convert light into heat, which not only kills tumor cells via hyperthermia in photothermal therapy (PTT), but also accelerates the degradation of Fe/DOX NCPs to release Fe3+ and DOX. The liberated Fe3+ can be used to catalyze hydrogen peroxide via the Fenton reaction to produce highly toxic hydroxyl radicals (˙OH) in chemodynamic therapy (CDT). The released DOX and the exposed Cu(DDC)2 can cause significant cell death in combined chemotherapy via a superimposed effect. In vitro and in vivo results prove that Cu(DDC)2@Fe/DOX NPs with laser irradiation present remarkable anticancer performances in hyperthermia-enhanced chemo-/CDT. Therefore, this study provides a new strategy for highly efficient synergistic cancer therapy.

Biomimetic Gold Nanorods Modified with Erythrocyte Membranes for Imaging-Guided Photothermal/Gene Synergistic Therapy.

Pancreatic cancer (PC) is one of the most malignant cancers that develops rapidly and carries a poor prognosis. Synergistic cancer therapy strategy could enhance the clinical efficacy compared to either treatment alone. In this study, gold nanorods (AuNRs) were used as siRNA delivery vehicles to interfere with the oncogenes of KRAS. In addition, AuNRs were one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser and achieve rapid photothermal therapy for malignant cancer cells. Modification of the erythrocyte membrane and antibody Plectin-1 occurred on the surface of the AuNRs, making them a promising target nanocarrier for enhancing antitumor effects. As a result, biomimetic nanoprobes presented advantages in biocompatibility, targeting capability, and drug-loading efficiency. Moreover, excellent antitumor effects have been achieved by synergistic photothermal/gene treatment. Therefore, our study would provide a general strategy to construct a multifunctional biomimetic theranostic multifunctional nanoplatform for preclinical studies of PC.

A Versatile Theranostic Nanoplatform with Aggregation-Induced Emission Properties: Fluorescence Monitoring, Cellular Organelle Targeting, and Image-Guided Photodynamic Therapy.

Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT.

Dual-Targeting and Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Therapy Boosted by Ascorbic Acid-Induced H2O2 in Situ Self-Supply.

Tumor-specific targeting and tumor visualization are major obstacles for clinical diagnosis and treatment. Herein, a dual-targeted "all-in-one" nanoplatform (FAA@CM) for trimodal imaging-guided photothermal/chemodynamic synergistic therapy was successfully synthesized by encapsulating Fe3O4, Ag2S, and ascorbic acid with the 4T1 cell membrane. The dual-targeting capability derived from 4T1 cell membrane cloaking and magnetic targeting enables the highly precise tumor-specific delivery of FAA@CM. Fe2+ released from FAA@CM in a weakly acidic tumor microenvironment can trigger the Fenton reaction to achieve chemodynamic therapy (CDT). The photothermal performance of FAA@CM not only enables photothermal therapy but also promotes the CDT effect. In order to relieve H2O2 deficiency, a biosafe H2O2 prodrug, ascorbic acid, was introduced to greatly increase the H2O2 concentration in tumors, promoting the Fenton reaction to produce more •OH to enhance the oxidative damage to tumors. Interestingly, FAA@CM exhibits trimodal imaging capabilities, including second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging, photoacoustic imaging, and magnetic resonance imaging, which can guide the laser irradiation, achieving complete elimination of 4T1 tumors in BALB/c mice. This work provided a novel dual-targeted, multifunctional theranostic nanoplatform for highly effective tumor therapy.

Interfacial engineered iron oxide nanoring for T2-weighted magnetic resonance imaging-guided magnetothermal-chemotherapy.

Due to no penetration depth limitation, low cost, and easy control, magnetic nanoparticles mediated magnetic hyperthermia therapy (MHT) has shown great potential in experimental and clinal treatments of various diseases. However, the low heating conversion efficiencies and short circulation times are major drawback for most existing magnetic-thermal materials. Additionally, single MHT treatment always leads to resistance and recurrence. Herein, a highly efficient magnetic-thermal conversion, ferrimagnetic vortex nanoring Fe3O4 coated with hyaluronic acid (HA) nanoparticles (Fe3O4@HA, FVNH NPs) was firstly constructed. Additionally, the doxorubicin (DOX) was successfully enclosed inside the FVNH and released remotely for synergetic magnetic–thermal/chemo cancer therapy. Due to the ferrimagnetic vortex-domain state, the ring shape Fe3O4 displays a high specific absorption rate (SAR) under an external alternating magnetic field (AMF). Additionally, antitumor drug (DOX) can be encapsulated inside the single large hole of FVNH by the hyaluronic acid (HA) shell and quickly released in response the tumor acidic microenvironments and AMF. What’s more, the non-loaded FVNH NPs show good biocompatibility but high cytotoxicity after loading DOX under AMF. Furthermore, the synthesized FVNH can efficiently reduce the transverse relaxation time and enhance negative magnetic resonance imaging (MRI). The impressive in vivo systemic therapeutic efficacy of FVNH was also proved in this work. Taken together, the results of this study demonstrate that the synthesized FVNH NPs offer the promise of serving as multifunctional theranostic nanoplatforms for medical imaging-guided tumor therapies.

Organic Theranostic Nanoplatform with Enhanced Fluorescence and Singlet Oxygen Quantum Yield for Tumor-Targeting Image-Guided Photodynamic/Photothermal Synergistic Therapy

The development of biocompatible therapeutic agents to achieve tumor-targeting photothermal/photodynamic synergistic therapy under imaging guidance is crucial for effective cancer phototherapy. Herein, we elaborately designed an organic theranostic nanoplatform, Ce6@HA-Cys-TTDTT nanoparticles (NPs), in which the active targeting moiety hyaluronic acid (HA) was conjugated with a hydrophobic conjugated oligomer TTDTT through the side chain of cystamine (Cys) to form an amphiphilic polymer, and then an excellent photosensitizer chlorin e6 (Ce6) was encapsulated by self-assembly. Bithiophenyl diketopyrrolopyrrole (TDPP) and triphenylamine were utilized as the acceptor (A) and donor (D), respectively, to construct the D–A–D molecule TTDTT, which served as an excellent photothermal agent with a moderate 1O2 quantum yield and quenched fluorescence (FL) in HA-Cys-TTDTT NPs. However, Ce6@HA-Cys-TTDTT NPs exhibited obviously higher 1O2 quantum yields (ΦΔ = 53.0%) and FL intensity than HA-Cys-TTDTT NPs (ΦΔ = 29.6%) and free Ce6 under laser irradiation at 635 nm and still maintained a high photothermal conversion efficiency (η = 37.7%). These results may be attributed to the efficient energy transfer from TTDTT to Ce6 in Ce6@HA-Cys-TTDTT NPs and the facilitation of the transition of singlet-to-triplet excited state via an intersystem crossing pathway. Ce6@HA-Cys-TTDTT NPs presented high tumor targeting capability in FL/thermal imaging in vivo and significant advantages over free Ce6 in long-term FL imaging in vivo. The remarkable antitumor efficacy of Ce6@HA-Cys-TTDTT NPs under a single wavelength laser irradiation was confirmed through in vitro and in vivo experiments. In this study, a multifunctional organic theranostic nanoplatform was designed to enhance the effect of tumor phototherapy, benefiting from the tumor-targeting multimodal imaging-guided photodynamic/photothermal synergistic therapy.

Nano-Metal-Organic Framework Decorated With Pt Nanoparticles as an Efficient Theranostic Nanoprobe for CT/MRI/PAI Imaging-Guided Radio-Photothermal Synergistic Cancer Therapy.

The multifunctional theranostic nanoplatforms, which can realize changing the contrasts of medical images and enhance cancer therapies simultaneously, have attracted tremendous attention from chemists and medicine in past decades. Herein, a nanoscale metal–organic framework-based material was first synthesized and then decorated with platinum (NMOF545@Pt) successfully for multimodal imaging-guided synergistic cancer therapy. The obtained NMOF545@Pt is advantageous in shortening the longitudinal relaxation time (T1), enhancing photoacoustic effects, and elevating X-ray absorption efficiently. Thus, the enchantments of tripe imaging modalities, computed tomography (CT)/magnetic resonance imaging (MRI)/photoacoustic imaging (PAI), were realized with NMOF545@Pt administration simultaneously and can be cleared from the mice. Meanwhile, in vitro and in vivo experiments demonstrate that the synthesized NMOF545@Pt can dramatically increase photothermal therapy (PTT) and radiotherapy (RT) efficacy. Convincing evidence proves that tumor growth can be wholly inhibited without noticeable side effects or organ damage. The results demonstrated the promise of multifunctional nanocomposites NMOF545@Pt to improve biomedical imaging and synergistic tumor treatments.

Multifunctional theranostic nanoplatform loaded with autophagy inhibitor for enhanced photothermal cancer therapy under mild near-infrared irradiation.

Photothermal therapy (PTT) usually causes hyperthermia and damages healthy tissues. Developing a PTT platform with enhanced therapeutic effects and reduced side effects to normal tissues attracts increasing attention. Herein, we developed a multifunctional theranostic nanoplatform using poly(lactic-co-glycolic acid) (PLGA) loaded with near-infrared (NIR) photothermal agent (new indocyanine green IR820), fluorescence imaging agent (ZnCdSe/ZnS quantum dots, QDs) and autophagy inhibitor (chloroquine, CQ). These PLGA/IR820/Fluorescence imaging agent/CQ co-loading nanoparticles (termed PIFC NPs) displayed photothermal effects, enhanced the stability of IR820 in vivo, and enabled QDs to have stable fluorescent signals in vitro and in vivo. The PIFC NPs with particle size around 240nm aggregated to tumor sites through the high permeability and retention effects of solid tumors. The intracellular delivery of CQ molecules through PIFC NPs significantly attenuated the degradation of autophagic lysosomes in tumor cells and effectively inhibited the autophagy mediated repair of photothermal damaged cells. Under milder NIR irradiation conditions, PIFC NPs exhibited high antitumor effect. By regulating autophagy, PTT can be effectively sensitized, which will provide a new idea for future cancer treatment research.

Nanoscale Hf-hematoporphyrin frameworks for synergetic sonodynamic/radiation therapy of deep-seated tumors

Most of tumors are located in deep-depth of animals, and the therapy of deep-seated tumors remains a severe challenge due to the performance reduction of promising technologies including phototherapy. To solve the problem, herein we have developed a hafnium-hemoporfin frameworks (HfHFs) as multifunctional theranostic nanoplatforms for synergetic sonodynamic therapy (SDT) and radiation therapy (RT) of deep-seated tumors. HfHFs are constructed by a sonication-assisted assembly route with hematoporphyrin monomethyl ether (HMME) sonosensitizer molecules as bridging linkers and Hf4+ as metal nodes. The resulting HfHFs sample is composed of spherical nanoparticles with size of 90–130 nm, and then surface-modified with DSPE-PEG to improve the water-dispersity. Under ultrasound (US) irradiation, HMME ligands in HfHFs can be motivated to produce singlet oxygen (1O2) due to sonodynamic effect. When the HfHFs sample is exposed by X-ray, the high atomic-number Hf4+ in the HfHFs can effectively absorb X-ray to increase RT effect by producing hydroxyl radicals (•OH). When HfHFs dispersion is intravenously injected in the tumor-bearing mice, the tumor can be monitored by CT imaging. Moreover, the deep-seated tumors coated by tissue barriers can be suppressed effectively by the synergistic SDT and RT, which is better than that of SDT or RT alone. Therefore, HfHFs can be employed as a novel nanoagent for the SDT-RT of deep-seated tumors.

Gold/Pentablock Terpolymer Hybrid Multifunctional Nanocarriers for Controlled Delivery of Tamoxifen: Effect of Nanostructure on Release Kinetics.

Here, we describe the preparation and characterization of organic/inorganic hybrid polymer multifunctional nanocarriers. Novel nanocomposites of gold nanoparticles using pH-responsive coordination pentablock terpolymers of poly(ε-caprolactone)-b-poly(ethylene oxide)-b-poly(2-vinylpyridine)-b-poly(ethylene oxide)-b-poly(ε-caprolactone), bearing or not bearing partially quaternized vinylpyridine moieties, were studied. The template morphology of the coordination pentablock terpolymer at physiological pH ranges from crew-cut to multicompartmentalized micelles which can be tuned by chemical modification of the central block. Additionally, the presence of 2VP groups allows the coordination of gold ions, which can be reduced in situ to construct gold@polymer nanohybrids. Furthermore, the possibility of tuning the gold distribution in the micelles, through partial quaternization of the central P2VP block, was also investigated. Various morphological gold colloidal nanoparticles such as gold@core-corona nanoparticles and gold@core-gold@corona nanoparticles were synthesized on the corresponding template of the pentablock terpolymer, first by coordination with gold ions, followed by reduction with NaBH4. The pentablock and gold@pentablock nanoparticles could sparingly accommodate a water-soluble drug, Tamoxifen (TAX), in their hydrophobic micellar cores. The nanostructure of the nanocarrier remarkably affects the TAX delivery kinetics. Importantly, the hybrid gold@polymer nanoparticles showed prolonged release profiles for the guest molecule, relative to the corresponding bare amphiphilic pentablock polymeric micelles. These Gold@pentablock terpolymer hybrid nanoparticles could act as a multifunctional theranostic nanoplatform, integrating sustainable pH-controlled drug delivery, diagnostic function and photothermal therapy.

Tumor‐specific and photothermal‐augmented chemodynamic therapy by ferrocene‐carbon dot‐crosslinked nanoparticles

AbstractExtensive research have been devoted to the exploration of multifunctional theranostic agents for cancer, but the poor tumor specificity and unsatisfactory treatment efficacy are some of the critical obstacles for their clinical translations. Herein, ferrocene‐carbon dot‐crosslinked nanoparticles (Fc‐CD NPs) were designed and fabricated for achieving highly specific and photothermal‐augmented chemodynamic therapy (CDT). The Fc‐CD NPs were found not only to inherit the immanent fluorescence, photoacoustic, and photothermal properties of carbon dots (CDs), but also be endowed with CDT that could occur selectively in tumor microenvironment (TME) due to the presence of Fc for triggering Fenton reaction. Moreover, the enlarged particle size of Fc‐CD NPs facilitated their effective accumulation at tumor sites, thus realizing great improvement for antitumor treatment outcomes. Once docking at tumor and being exposed to 660 nm laser irradiation, significantly amplified CDT effect of Fc‐CD NPs was observed due to heat‐accelerating generation of reactive oxygen species (ROS). More interestingly, since the produced ROS could in turn alleviate the thermal‐resistance of photothermal therapy (PTT), the therapeutic efficiency of integrated PTT and CDT was synergized to the maximum extent. This study on the one hand provides a facile approach to fabricate CDs‐based multifunctional theranostic nanoplatform with enhanced tumor accumulation and specificity, on the other hand emphasizes the merits of synergizing mutually beneficial therapeutic modalities for more efficient cancer therapy.

Structural symmetry effects in plasmonic metal-semiconductor hybrid heterostructures for multimodal cancer phototheranostics

The structural symmetry is of great importance for optical and chemical behaviors of a complex plasmonic nanostructure system. However, the influence of structural symmetry breaking has been rarely studied in metal–semiconductor heterostructures for cancer phototheranostics. Herein, we present a systematic investigation on cancer phototheranostics of plasmonic Au-Cu2-xSe nanocrystals (GCS NCs) with different structural symmetries. These GCS NCs are capable of photoacoustic (PA)/computed tomography (CT) diagnostic imaging for tumor visualization and chemodynamic therapy (CDT)/photothermal therapy (PTT) of cancer. We theoretically and experimentally demonstrate much superior near-infrared II (NIR-II) plasmonic and photothermal properties from Janus-GCS NCs because of much stronger plasmonic coupling effects compared with concentric and non-concentric GCS core/shell structures. In addition, more efficient OH production via the combined Fenton-like effects and photocatalytic reaction is evidenced for Janus-GCS NCs with a further enhancement upon the NIR-II laser irradiation. Janus-GCS NCs as a multifunctional theranostic nanoplatform have been demonstrated for highly efficient PA/CT imaging-guided CDT/PTT synergistic cancer therapy in vivo with efficient glutathione depletion. This study highlights the importance of structural symmetry in plasmonic metal–semiconductor heterostructures for cancer phototheranostics.

Iron ion and sulfasalazine-loaded polydopamine nanoparticles for Fenton reaction and glutathione peroxidase 4 inactivation for enhanced cancer ferrotherapy

Ferroptosis shows promising potential in tumor treatment; however, factors that compromise the efficiency of the Fenton catalyst have limited its therapeutic effectiveness. We developed a polydopamine-based nanoplatform constructed with ferric ion and sulfasalazine-loaded nanoparticles (Fe(III)PP@SAS NPs) for dual-functional ferrotherapy strategy of “sword and shield” through enhanced Fenton reaction and inactivation of glutathione peroxidase 4 (GPX4), respectively. Both the Fenton reaction-based hydroxyl radical (·OH) production and sulfasalazine-driven GPX4 inhibition induced ferroptotic cell death, thus achieving synergistic cancer therapy. Near-infrared light irradiation and acidic tumor microenvironment enhanced the release of ferric ions and sulfasalazine from the Fe(III)PP@SAS NPs. In addition, the released iron ions underwent valence state change due to Fenton reaction and thus provided a supplementary T1-weighted signal for in situ visualization of the tumor based on magnetic resonance imaging. The Fe(III)PP@SAS NPs exhibited high pro-ferroptosis performance by utilizing ·OH radicals as a “sword” to attack cancer cells and the GPX4 inhibitor to break down the “shield” of cancer cells, thus showing potential for cancer treatment. Statement of significanceSeveral strategies of cancer therapy based on ferroptosis have emerged in recent years, which have provided new insights into designing materials for therapeutic applications. The antitumor efficacy of ferroptosis is, however, still unsatisfactory, mainly because of insufficient intracellular pro-ferroptotic stimuli. In the current study, we report a multifunctional theranostic nanoplatform, namely Fe(III)PP@SAS, with three-fold synergistic effect; this nanoplatform has excellent theranostic potential with multifunctional ferrotherapy.

Bioactive Composite Nanoparticles for Effective Microenvironment Regulation, Neuroprotection, and Cell Differentiation.

Brain injuries typically result in neural tissue damage and trigger a permanent neurologic deficit. Current methods exhibit limited effects due to the harsh microenvironment of injury regions rich in reactive oxygen species (ROS). Herein, a microenvironment regulation combined with cellular differentiation strategy is designed for repairing injured nerves. We prepare PMNT/F@D-NP nanoparticles comprising a bioactive polythiophene derivative (PMNT) and fullerenol as a multifunctional theranostic nanoplatform. PMNT/F@D-NPs can significantly reduce the accumulation of ROS in the simulated ischemic brain injury trial and inhibit cell apoptosis due to the effective free radical scavenging ability of fullerenol. Interestingly, the bioactive PMNT/F@D-NPs can promote the proliferation and differentiation of neurons, confirmed by immunofluorescence and western blotting studies. This newly developed strategy exhibits a combinatorial therapeutic effect by promoting nerve cell survival and differentiation while improving the microenvironment in the damaged area, which paves the way for the rational design of multifunctional agents for brain injury therapy.

Near infrared triggered chemo-PTT-PDT effect mediated by glioma directed twin functional-chimeric peptide-decorated gold nanoroses.

The successful application of nanomedicine against glioma is basically hooked on to the fabrication of specific and efficient glioma targeted multifunctional theranostics. Herein, through an easy synthetic methodology, we fabricated a type of novel multifunctional theranostic nanoplatform comprising of anisotropic gold nanoroses (AuNs) co-loaded with doxorubicin (DOX) and the near-infrared (NIR) active/responsive dye, indocyanine green (ICG). The tailored nanotheranostics upon being exposed to NIR laser helped in achieving combinatorial chemo-phototherapy along with optical cell imaging. BBB/glioma-targeting ability was realized by amalgamating the AuNs with a naive peptide drug with BBB-glioma targeting and anti-glioma twin functionality. Efficacy studies carried out in C6 cells and spheroids demonstrated heightened synergistic glioma chemo-PDT-PTT effect (~85% ablation in C6 cells and~88% in C6 spheroids) by the AuNDIPs as compared to the individual therapeutic entities. Here, the AuNs derived nanophototheranostics with in force targeting and on-demand drug release nature will further aid in abolishing chemotherapy associated adverse events by adopting a combinatorial approach for synergistic glioma eradication.

Cooperative coordination-mediated multi-component self-assembly of “all-in-one” nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO43−) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an “all-in-one” theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Fibronectin-Coated Metal-Phenolic Networks for Cooperative Tumor Chemo-/Chemodynamic/Immune Therapy via Enhanced Ferroptosis-Mediated Immunogenic Cell Death.

The development of nanomedicine formulations to overcome the disadvantages of traditional chemotherapeutic drugs and integrate cooperative theranostic modes still remains challenging. Herein, we report the facile construction of a multifunctional theranostic nanoplatform based on doxorubicin (DOX)-loaded tannic acid (TA)-iron (Fe) networks (for short, TAF) coated with fibronectin (FN) for combination tumor chemo-/chemodynamic/immune therapy under the guidance of magnetic resonance (MR) imaging. We show that the DOX-TAF@FN nanocomplexes created through in situ coordination of TA and Fe(III) and physical coating with FN have a mean particle size of 45.0 nm, are stable, and can release both DOX and Fe in a pH-dependent manner. Due to the coexistence of the TAF network and DOX, significant immunogenic cell death can be caused through enhanced ferroptosis of cancer cells via cooperative Fe-based chemodynamic therapy and DOX chemotherapy. Through further treatment with programmed cell death ligand 1 antibody for an immune checkpoint blockade, the tumor treatment efficacy and the associated immune response can be further enhanced. Meanwhile, with FN-mediated targeting, the DOX-TAF@FN platform can specifically target tumor cells with high expression of αvβ3 integrin. Finally, the TAF network also enables the DOX-TAF@FN to have an r1 relaxivity of 6.1 mM-1 s-1 for T1-weighted MR imaging of tumors. The developed DOX-TAF@FN nanocomplexes may represent an updated multifunctional nanosystem with simple compositions for cooperative MR imaging-guided targeted chemo-/chemodynamic/immune therapy of tumors.

Functionalized Au@Cu-Sb-S Nanoparticles for Spectral CT/Photoacoustic Imaging-Guided Synergetic Photo-Radiotherapy in Breast Cancer.

BackgroundRadiotherapy (RT) is clinically well-established cancer treatment. However, radioresistance remains a significant issue associated with failure of RT. Phototherapy-induced radiosensitization has recently attracted attention in translational cancer research.MethodsCu-Sb-S nanoparticles (NPs) coated with ultra-small Au nanocrystals (Au@Cu-Sb-S) were synthesized and characterized. The biosafety profiles, absorption of near-infrared (NIR) laser and radiation-enhancing effect of the NPs were evaluated. In vitro and in vivo spectral computed tomography (CT) imaging and photoacoustic (PA) imaging were performed in 4T1 breast cancer-bearing mice. The synergetic radio-phototherapy was assessed by in vivo tumor inhibition studies.ResultsAu@Cu-Sb-S NPs were prepared by in situ growth of Au NCs on the surface of Cu-Sb-S NPs. The cell viability experiments showed that the combination of Au@Cu-Sb-S+NIR+RT was significantly more cytotoxic to tumor cells than the other treatments at concentrations above 25 ppm Sb. In vitro and in vivo spectral CT imaging demonstrated that the X-ray attenuation ability of Au@Cu-Sb-S NPs was superior to that of the clinically used Iodine, particularly at lower KeV levels. Au@Cu-Sb-S NPs showed a concentration-dependent and remarkable PA signal brightening effect. In vivo tumor inhibition studies showed that the prepared Au@Cu-Sb-S NPs significantly suppressed tumor growth in 4T1 breast cancer-bearing mice treated with NIR laser irradiation and an intermediate X-ray dose (4 Gy).ConclusionThese results indicate that Au@Cu-Sb-S integrated with spectral CT, PA imaging, and phototherapy-enhanced radiosensitization is a promising multifunctional theranostic nanoplatform for clinical applications.

Ultrasmall PEI-Decorated Bi2Se3 Nanodots as a Multifunctional Theranostic Nanoplatform for in vivo CT Imaging-Guided Cancer Photothermal Therapy.

Bi-based nanomaterials, such as Bi2Se3, play an important part in biomedicine, such as photothermal therapy (PTT) and computed tomography (CT) imaging. Polyethylenimine (PEI)-modified ultrasmall Bi2Se3 nanodots were prepared using an ultrafast synthetic method at room temperature (25°C). Bi2Se3 nanodots exhibited superior CT imaging performance, and could be used as effective photothermal reagents owing to their broad absorption in the ultraviolet–visible–near infrared region. Under irradiation at 808 nm, PEI-Bi2Se3 nanodots exhibited excellent photothermal-conversion efficiency of up to 41.3%. Good biocompatibility and significant tumor-ablation capabilities were demonstrated in vitro and in vivo. These results revealed that PEI-Bi2Se3 nanodots are safe and a good nanotheranostic platform for CT imaging-guided PTT of cancer.