PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy

Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T₁-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy.     

Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal imaging and photothermal ablation of cancer

The combination of CT imaging and photoacoustic (PA) imaging represents not only high resolution and ease of forming 3D visual image for locating tissues of interest, but also good soft tissue contrast and excellent high sensitivity, which is very beneficial to the precise guidance for photothermal therapy (PTT). The near infrared (NIR) absorbing Au nanostructures take advantages to operate as a CT contrast agent due to high absorption coefficient of X-ray and outstanding biocompatibility, but show obvious deficiency for PA imaging and PTT because of low photostability. Attacking this problem head on, the Au nanoparticles (NPs) were coated with Prussian blue (PB) which is a typical FDA-approved drug in clinic for safe and effective treatment of radioactive exposure. The obtained core/shell NPs of Au@PB NPs of 17.8 ± 2.3 nm were found to be an excellent photoabsorbing agent for both PTT and PA imaging due to high photostability and high molar extinction coefficient in NIR region. Their gold core of 9.1 ± 0.64 nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100 mm³ sized tumors in nude mice could be completely ablated without recurrence. Such versatile nanoparticles integrating effective cancer diagnosis with noninvasive therapy might bring opportunities to future cancer therapy.     

Encapsulating tantalum oxide into polypyrrole nanoparticles for X-ray CT/photoacoustic bimodal imaging-guided photothermal ablation of cancer

A nanotheranostic agent has been readily fabricated by encapsulating tantalum oxide (TaO_x) nanoparticles (NPs) into polypyrrole (PPy) NPs via a facile one-step chemical oxidation polymerization for bimodal imaging guided photothermal ablation of tumor. It was proved that the obtained composite nanoparticles (TaO_x@PPy NPs) with an average diameter around 45 nm could operate as an efficient bimodal contrast agent to simultaneously enhance X-ray CT and photoacoustic (PA) imaging greatly in vivo. Systemically administered TaO_x@PPy NPs could passively accumulate at the tumor site during the blood circulation, which was proved by both CT and PA imaging. In addition, the in vivo therapeutic examinations showed that TaO_x@PPy NPs exhibited significant photothermal cytotoxicity under near infrared laser irradiation. The tumor growth inhibition was evaluated to be 66.5% for intravenously injection and 100% for intratumoral injection, respectively. This versatile agent can be developed as a smart and promising nanoplatform that integrates multiple capabilities for both accurate diagnosing and precise locating of cancerous tissue, as well as effective photoablation of tumor.     

Graphene oxide-BaGdF5 nanocomposites for multi-modal imaging and photothermal therapy

By using a solvothermal method in the presence of polyethylene glycol (PEG), BaGdF₅ nanoparticles are firmly attached on the surface of graphene oxide (GO) nanosheets to form the GO/BaGdF₅/PEG nanocomposites. The resulting GO/BaGdF₅/PEG shows low cytotoxicity, positive magnetic resonance (MR) contrast effect and better X-ray attenuation property than Iohexol, which enables effective dual-modality MR and X-ray computed tomography (CT) imaging of the tumor model in vivo. The enhanced near-infrared absorbance, good photothermal stability and efficient tumor passive targeting of GO/BaGdF₅/PEG result in the highly efficient photothermal ablation of tumor in vivo after intravenous injection of GO/BaGdF₅/PEG and the following 808-nm laser irradiation (0.5 W/cm²). The histological and biochemical analysis data reveal no perceptible toxicity of GO/BaGdF₅/PEG in mice after treatment. These results indicate potential application of GO/BaGdF₅/PEG in dual-modality MR/CT imaging and photothermal therapy of cancers.     

FeS nanoplates as a multifunctional nano-theranostic for magnetic resonance imaging guided photothermal therapy

In this work, we develop magnetic iron sulfide (FeS) nanoplates as a theranostic agent for magnetic resonance (MR) imaging-guided photothermal therapy of cancer. FeS nanoplates are synthesized via a simple one-step method and then functionalized with polyethylene glycol (PEG). The obtained PEGylated FeS (FeS-PEG) nanoplates exhibit high NIR absorbance together with strong superparamagnetism. The r2 relaxivity of FeS-PEG nanoplates is determined to be 209.8 mm-1S-1, which appears to be much higher than that of iron oxide nanoparticles and several types of clinical approved T2-contrast agents. After intravenous (i.v.) injection, those nanoplates show high accumulation in the tumor as revealed by MR imaging. Highly effective photothermal ablation of tumors is then achieved in a mouse tumor model upon i.v. injection of FeS-PEG at a moderate dose (20 mg/kg) followed by 808-nm NIR laser irradiation. Importantly, it has been found that PEGylated FeS nanoplates after systemic administration could be gradually excreted from major organs of mice, and show no appreciable toxicity to the treated animals even at a dose (100 mg/kg) 5 times as high as that used for imaging & treatment. Our results demonstrate that PEGylated FeS nanoplates may be a promising class of theranostic nano-agents with a good potential for future clinical translation.     

LaB6 nanoparticles with carbon-doped silica coating for fluorescence imaging and near-IR photothermal therapy of cancer cells

In this study, LaB₆ nanoparticles are used as a novel nanomaterial for near-infrared (NIR) photothermal therapy because they are cheaper than nanostructured gold, are easy to prepare and have an excellent NIR photothermal conversion property. Furthermore, the surface of LaB₆ nanoparticles is coated with a carbon-doped silica (C-SiO₂) shell to introduce a fluorescent property and improve stability and biocompatibility. The resulting LaB₆@C-SiO₂ nanoparticles retain the excellent NIR photothermal conversion property and exhibit a bright blue emission under UV irradiation or a green emission under visible irradiation. Using a HeLa cancer cell line, it is demonstrated that LaB₆@C-SiO₂ nanoparticles have no significant cytotoxicity, but their presence leads to remarkable cell death after NIR irradiation. In addition, from the observation of cellular uptake, the fluorescence labeling function of LaB₆@SiO₂ (LaB₆ core/SiO₂ shell) nanoparticles is also confirmed. These results suggest that LaB₆@C-SiO₂ nanoparticles may potentially serve as an efficient multifunctional nano-platform for simultaneous fluorescent imaging and NIR-triggered photothermal therapy of cancer cells.     

Magnetic and fluorescent graphene for dual modal imaging and single light induced photothermal and photodynamic therapy of cancer cells

Developing a simple and cost-effective strategy to diagnose and treat cancer with single and minimal dosage through noninvasive strategies are highly challenging. To make the theranostic strategy effective, single light induced photothermal and photodynamic reagent with dual modal imaging capability is highly desired. Herein, a simple non-covalent approach was adopted to immobilize hydrophobic silicon napthalocyanine bis (trihexylsilyloxide) (SiNc₄) photosensitizer onto water dispersible magnetic and fluorescent graphene (MFG) via π–π stacking to yield MFG–SiNc₄ functioned as a theranostic nanocarrier. Taking the advantage of broad near infra-red absorption (600–1200 nm) by graphene, photosensitizer of any wavelength within this range will facilitate the single light induced phototherapy. Phosphorescence spectra, singlet oxygen sensor green (SOSG) experiments, and 1,3-diphenyl isobenzofuran quenching studies confirm the generation of singlet ¹O₂ upon photoirradiation. Confocal microscopic images reveal successful internalization of MFG–SiNc₄ in HeLa cells; whereas T₂-weighted magnetic resonance images of MFG reveal a significant concentration dependent darkening effect. In vitro photodynamic/photothermal therapeutic studies on HeLa cells have demonstrated that the killing efficacy of MFG–SiNc₄ using a single light source is ∼97.9%, presumably owing to the combined effects of generating reactive oxygen species, local heating, and induction of apoptosis. The developed MFG–SiNc₄ may thus be utilized as a potential theranostic nanocarrier for dual modal imaging and phototherapy of cancer cells with single light source for time and cost effective treatments with a minimal therapy dose.     

Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy

It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(l-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake. The micelles achieve the preferable biodistribution and long-term retention of carbocyanine dyes at tumor, which result in enhanced NIRF imaging by generating stable retention of NIRF signals at both hypervascular and hypovascular tumors during a long-term imaging period of up to 8 day, accompanying with negligible noise at normal tissues. The photostability of carbocyanine dye (Cypate) plays an important role for long-term cancer imaging with enhanced SNR. Moreover, the micelles exhibit severe photothermal damage on cancer cells via the destabilization of subcellular organelles upon photoirradiation, causing superior photothermal tumor regress. The micelles act as a powerful theranostic nanocarrier for simultaneous cancer imaging with high contrast and superior photothermal therapy.     

Near-infrared dye bound albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy

Development of theranostic agent for imaging-guided photothermal therapy has been of great interest in the field of nanomedicine. However, if fluorescent imaging and photothermal ablation are conducted with the same wavelength of light, the requirements of the agent's quantum yield (QY) for imaging and therapy are controversial. In this work, our synthesized near-infrared dye, IR825, is bound with human serum albumin (HSA), forming a HSA-IR825 complex with greatly enhanced fluorescence under 600 nm excitation by as much as 100 folds compared to that of free IR825, together with a rather high absorbance but low fluorescence QY at 808 nm. Since high QY that is required for fluorescence imaging would result in reduced photothermal conversion efficiency, the unique optical behavior of HSA-IR825 enables imaging and photothermal therapy at separated wavelengths both with optimized performances. We thus use HSA-IR825 for imaging-guided photothermal therapy in an animal tumor model. As revealed by in vivo fluorescence imaging, HSA-IR825 upon intravenous injection shows high tumor uptake likely owing to the enhanced permeability and retention effect, together with low levels of retentions in other organs. While HSA is an abundant protein in human serum, IR825 is able to be excreted by renal excretion as evidenced by high-performance liquid chromatography (HPLC). In vivo tumor treatment experiment is finally carried out with HSA-IR825, achieving 100% of tumor ablation in mice using a rather low dose of IR825. Our work presents a safe, simple, yet imageable photothermal nanoprobe, promising for future clinical translation in cancer treatment.     

Hyaluronic acid-modified Fe3O4@Au core/shell nanostars for multimodal imaging and photothermal therapy of tumors

Development of multifunctional theranostic nanoplatforms for diagnosis and therapy of cancer still remains a great challenge. In this work, we report the use of hyaluronic acid-modified Fe₃O₄@Au core/shell nanostars (Fe₃O₄@Au-HA NSs) for tri-mode magnetic resonance (MR), computed tomography (CT), and thermal imaging and photothermal therapy of tumors. In our approach, hydrothermally synthesized Fe₃O₄@Ag nanoparticles (NPs) were used as seeds to form Fe₃O₄@Au NSs in the growth solution. Further sequential modification of polyethyleneimine (PEI) and HA affords the NSs with excellent colloidal stability, good biocompatibility, and targeting specificity to CD44 receptor-overexpressing cancer cells. With the Fe₃O₄ core NPs and the star-shaped Au shell, the formed Fe₃O₄@Au-HA NSs are able to be used as a nanoprobe for efficient MR and CT imaging of cancer cells in vitro and the xenografted tumor model in vivo. Likewise, the NIR absorption property enables the developed Fe₃O₄@Au-HA NSs to be used as a nanoprobe for thermal imaging of tumors in vivo and photothermal ablation of cancer cells in vitro and xenografted tumor model in vivo. This study demonstrates a unique multifunctional theranostic nanoplatform for multi-mode imaging and photothermal therapy of tumors, which may find applications in theranostics of different types of cancer.     

Supramolecular adducts of squaraine and protein for noninvasive tumor imaging and photothermal therapy in vivo

Extensive efforts have been devoted to the development of near-infrared (NIR) dye-based imaging probes and/or photothermal agents for cancer theranostics in vivo. However, the intrinsic chemical instability and self-aggregation properties of NIR dyes in physiological condition limit their widely applications in the pre-clinic study in living animals. Squaraine dyes are among the most promising NIR fluorophores with high absorption coefficiencies, bright fluorescence and photostability. By introducing dicyanovinyl groups into conventional squaraine (SQ) skeleton. These acceptor-substituted SQ dyes not only show superior NIR fluorescence properties (longer wavelength, higher quantum yield) but also exhibit more chemical robustness. In this work, we demonstrated highly stable and biocompatible supramolecular adducts of SQ and the natural carrier protein, i.e., bovine serum albumin (BSA) (SQ⊂BSA) for tumor targeted imaging and photothermal therapy in vivo. SQ was selectively bound to BSA hydrophobic domain via hydrophobic and hydrogen bonding interactions with up to 80-fold enhanced fluorescence intensity. By covalently conjugating target ligands to BSA, the SQ⊂BSA was capable of targeting tumor sites and allowed for monitoring the time-dependent biodistribution of SQ⊂BSA, which consequently determined the protocol of photothermal therapy in vivo. We envision that this supramolecular strategy for selectively binding functional imaging agents and/or drugs into human serum albumin might potentially utilize in the preclinical and even clinic studies in the future.     

Self-assembled PEG-IR-780-C13 micelle as a targeting,safe and highly-effective photothermal agent for in vivo imaging and cancer therapy

IR-780, a representative hydrophobic near-infrared (NIR) fluorescence dye, is capable of fluorescently imaging and photothermal therapy in vitro and in vivo. However, insolubility in all pharmaceutically acceptable solvents limits its further biological applications. To increase solubility, we developed a novel self-assembled IR-780 containing micelle (PEG-IR-780-C13) based on the structural modification of IR-780. Briefly, a hydrophilic PEG₂₀₀₀ was modified on the one side of IR-780, and the hydrophobic carbon chain on the other side was extended from C3 to C16 (additional C13 carbon chain). The modification provides a better self-assemble capability, improved water solubility and higher stability. In addition, PEG-IR-780-C13 micelles are specifically targeted to the tumor after intravenous injection and can be used for tumor imaging. The in vitro cell viability assays and in vivo photothermal therapy experiments indicated that CT-26 cells or CT-26 xenograft tumors can be effectively ablated by combining PEG-IR-780-C13 micelles with 808 nm laser irradiation. More importantly, no significant toxicity can be observed after intravenous administration of the therapeutic dose of generated micelles. Overall, our micelles may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

Dual functional AuNRs@MnMEIOs nanoclusters for magnetic resonance imaging and photothermal therapy

A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T₂-weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r₂ relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were – 70.4 ± 4.3% versus – 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy.     

An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery

A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a ‘photothermal ablation assisted surgery’ strategy, promising for future clinical cancer treatment.     

Fluorescent porous carbon nanocapsules for two-photon imaging,NIR/pH dual-responsive drug carrier,and photothermal therapy

An efficient nanomedical platform that can combine two-photon cell imaging, near infrared (NIR) light and pH dual responsive drug delivery, and photothermal treatment was successfully developed based on fluorescent porous carbon-nanocapsules (FPC-NCs, size ∼100 nm) with carbon dots (CDs) embedded in the shell. The stable, excitation wavelength (λ_ex)-tunable and upconverted fluorescence from the CDs embedded in the porous carbon shell enable the FPC-NCs to serve as an excellent confocal and two-photon imaging contrast agent under the excitation of laser with a broad range of wavelength from ultraviolet (UV) light (405 nm) to NIR light (900 nm). The FPC-NCs demonstrate a very high loading capacity (1335 mg g⁻¹) toward doxorubicin drug benefited from the hollow cavity structure, porous carbon shell, as well as the supramolecular π stacking and electrostatic interactions between the doxorubicin molecules and carbon shell. In addition, a responsive release of doxorubicin from the FPC-NCs can be activated by lowering the pH to acidic (from 7.4 to 5.0) due to the presence of pH-sensitive carboxyl groups on the FPC-NCs and amino groups on doxorubicin molecules. Furthermore, the FPC-NCs can absorb and effectively convert the NIR light to heat, thus, manifest the ability of NIR-responsive drug release and combined photothermal/chemo-therapy for high therapeutic efficacy.     

Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy

Theranostics, the combination of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Herein, we develop multifunctional nanoparticles (MFNPs) with highly integrated functionalities including upconversion luminescence, superparamagnetism, and strong optical absorption in the near-infrared (NIR) region with high photostability. In vivo dual modal optical/magnetic resonance imaging of mice uncovers that by placing a magnet nearby the tumor, MFNPs tend to migrate toward the tumor after intravenous injection and show high tumor accumulation, which is ∼8 folds higher than that without magnetic targeting. NIR laser irradiation is then applied to the tumors grown on MFNP-injected mice under magnetic tumor-targeting, obtaining an outstanding photothermal therapeutic efficacy with 100% of tumor elimination in a murine breast cancer model. We present here a strategy for multimodal imaging-guided, magnetically targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics.     

Engineering of perfluorooctylbromide polypyrrole nano-/microcapsules for simultaneous contrast enhanced ultrasound imaging and photothermal treatment of cancer

A versatile oil-in-water emulsion method has been explored for constructing water-dispersible polypyrrole (PPy) nano-/microcapsules with a soluble PPy complex as multifunctional photothermal agents for tumor ablation. In this work, both PPy nanocapsules (280.4 ± 79.0 nm) and microcapsules (1.31 ± 0.45 μm) with liquid perfluorooctylbromide (PFOB) core could be obtained by simply tuning the process energy for emulsion formation from ultrasonication to homogenization. Owing to the encapsulated liquid PFOB and strong near-infrared (NIR) absorption of PPy shell, the resulted PPy capsules showed great promise in ultrasound imaging guided photothermal ablation of tumor cells without inducing any significant side effect. Thus, it is anticipated that fine-tuning of the other encapsulated drugs or functional materials in PPy capsules would foster avenues for the development of multifunctional platforms for cancer treatments.     

Pluronic-encapsulated natural chlorophyll nanocomposites for in vivo cancer imaging and photothermal/photodynamic therapies

A great challenge in developing nanotechnologies for cancer diagnosis and therapy has been the combined functionalities required for complicated clinical procedures. Among all requirements, toxicity has been the major hurdle that has prevented most of the nano-carriers from clinical use. Here, we extracted chlorophyll (Chl) from vegetable and encapsulated it into polymer (pluronic F68, Plu) micelles for cancer imaging and therapy. The results showed that the Chl-containing nanocomposites were capable of mouse tumor targeting, and the nanocomposite fluorescence within the tumor sites remained at high intensity more than two days after tail-vein injection. It is interesting that oral administration with the nanocomposites was also successful for tumor target imaging. Furthermore, the dietary Chl was found to be able to efficiently convert near-infrared laser irradiation to heat. The growths of melanoma cells and mouse tumors were effectively inhibited after being treated with the nanocomposites and irradiation. The suppression of the tumors was achieved by laser-triggered photothermal and photodynamic synergistic effects of Chl. As a natural substance from vegetable, Chl is non-toxic, making it an ideal nano-carrier for cancer diagnosis and treatment. Based on the results of this research, the Plu–Chl nanocomposites have shown promise for future clinical applications.     

NIR-light-induced surface-enhanced Raman scattering for detection and photothermal/photodynamic therapy of cancer cells using methylene blue-embedded gold nanorod@SiO2 nanocomposites

Methylene blue-loaded gold nanorod@SiO₂ (MB-GNR@SiO₂) core@shell nanoparticles are synthesized for use in cancer imaging and photothermal/photodynamic dual therapy. For the preparation of GNR@SiO₂ nanoparticles, we found that the silica coating rate of hexadecylcetyltrimethylammonium bromide (CTAB)-capped GNRs is much slower than that of PEGylated GNRs due to the densely coated CTAB bilayer. Encapsulated MB molecules have both monomer and dimer forms that result in an increase in the photosensitizing effect through different photochemical pathways. As a consequence of the excellent plasmonic properties of GNRs at near-infrared (NIR) light, the embedded MB molecules showed NIR light-induced SERS performance with a Raman enhancement factor of 3.0 × 10¹⁰, which is enough for the detection of a single cancer cell. Moreover, the MB-GNR@SiO₂ nanoparticles exhibit a synergistic effect of photodynamic and photothermal therapies of cancer under single-wavelength NIR laser irradiation.     

Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy

The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent delivery vehicle used in anticancer therapy. However, the exact mechanisms of MSCs involved in tumor microenvironment are still not well defined. Molecular imaging technologies with the versatility in monitoring the therapeutic effects, as well as basic molecular and cellular processes in real time, offer tangible options to better guide MSCs mediated cancer therapy. In this study, an in situ breast cancer model was developed with MDA-MB-231 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP) into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC-MSCs simultaneously. We found that tumors were significantly inhibited by hUC-MSCs administration, and this effect was enhanced by ganciclovir (GCV) application. To further demonstrate the effect of hUC-MSCs on tumor cells in vivo, we employed the near infrared (NIR) imaging and the results showed that hUC-MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an invaluable tool in tracking cell delivery and tumor response to hUC-MSCs therapies as well as cellular and molecular processes in tumor.