Microfluidic Roadmap for Translational Nanotheranostics.

Nanotheranostic materials (NTMs) shed light on the mechanisms responsible for complex diseases such as cancer because they enable making a diagnosis, monitoring the disease progression, and applying a targeted therapy simultaneously. However, several issues such as the reproducibility and mass production of NTMs hamper their application for clinical practice. To address these issues and facilitate the clinical application of NTMs, microfluidic systems have been increasingly used. This perspective provides a glimpse into the current state-of-art of NTM research, emphasizing the methods currently employed at each development stage of NTMs and the related open problems. This work reviews microfluidic technologies used to develop NTMs, ranging from the fabrication and testing of a single NTM up to their manufacturing on a large scale. Ultimately, a step-by-step vision on the future development of NTMs for clinical practice enabled by microfluidics techniques is provided.

Theranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis.

Radiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500-1,700 nm) window modified by catalase, arginine-glycine-aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.

Biodegradable manganese engineered nanocapsules for tumor-sensitive near-infrared persistent luminescence/magnetic resonance imaging and simultaneous chemotherapy.

Rationale: Near-Infrared persistent luminescence (NIR-PL) nanomaterials that can continually emit low-energy photons after ceasing excitation has emerged as a new generation of theranostic nanoparticle drug delivery systems (NDDSs) for imaging-guided cancer therapy, which stems from their special ability to completely avoid tissue autofluorescence interference. However, unresponsive diagnostic capability, inefficient drug delivery, and poor biodegradability limit the efficacy of most reported NIR-PL-based NDDSs. Methods: Herein, a multifaceted tumor microenvironment (TME)-degradable theranostic drug delivery nanocapsule based on an ultrasmall persistent phosphor with a hollow mesoporous manganese-doped, DOX-loaded silica shell (Mn-ZGOCS-PEG) is developed to overcome the above drawbacks. Results: We demonstrate that the well-designed nanocapsule enables tumor-responsive controlled drug release with ameliorated therapeutic efficacy, TME-responsive autofluorescence interference-free NIR-PL tracing, and manganese-enhanced magnetic resonance (Mn-MR) monitoring for practical dual-modality image-guided antitumor treatment in vivo. Conclusion: Our results indicate that Mn-ZGOCS-PEG nanocapsules enable tumor-targeting augmented chemotherapy under the guidance of TME-responsive dual-MR/NIR-PL-modality imaging in vivo. We believe that our work provides a new paradigm for the development of smart NIR-PL-based NDDSs with ultrasensitive multimodal diagnostic capability, enhanced anticancer effect, and efficient biodegradability.

Constructing a Smartphone-Controlled Semiautomatic Theranostic System for Glucose Homeostasis in Diabetic Mice.

With the development of mobile communication technology, smartphones have been used in point-of-care technologies (POCTs) as an important part of telemedicine. Using a multidisciplinary design principle coupling electrical engineering, software development, synthetic biology, and optogenetics, the investigators developed a smartphone-controlled semiautomatic theranostic system that regulates blood glucose homeostasis in diabetic mice in an ultraremote-control manner. The present chapter describes how the investigators tailor-designed the implant architecture "HydrogeLED," which is capable of coharboring a designer-cell-carrying alginate hydrogel and wirelessly powered far-red light LEDs. Using diabetes mellitus as a model disease, the in vivo expression of insulin or human glucagon-like peptide 1 (shGLP-1) from HydrogeLED implants could be controlled not only by pre-set ECNU-TeleMed programs, but also by a custom-engineered Bluetooth-active glucometer in a semiautomatic and glycemia-dependent manner. As a result, blood glucose homeostasis was semiautomatically maintained in diabetic mice through the smartphone-controlled semiautomatic theranostic system. By combining digital signals with optogenetically engineered cells, the present study provides a new method for the integrated diagnosis and treatment of diseases.

Polymeric Nanoreactors as Emerging Nanoplatforms for Cancer Precise Nanomedicine.

How to precisely detect and effectively cure cancer which is defined as precise nanomedicine has drawn great attention worldwide. Polymeric nanoreactors which can in situ catalyze inert species into activated ones, can greatly increase imaging quality and enhance therapeutic effects along with decreased background interference and reduced serious side effects. After a brief introduction, the design and preparation of polymeric nanoreactors are discussed from the following aspects, that is, solvent-switch, pH-tuning, film rehydration, hard template, electrostatic interaction, and polymerization-induced self-assembly (PISA). Subsequently, the biomedical applications of these nanoreactors in the fields of cancer imaging, cancer therapy, and cancer theranostics are highlighted. The last but not least, conclusions and future perspectives about polymeric nanoreactors are given. It is believed that polymeric nanoreactors can bring a great opportunity for future fabrication and clinical translation of precise nanomedicine.

Membrane vesicles nanotheranostic systems: sources, engineering methods, and challenges.

Extracellular vesicles (EVs) are cell secretory native components with long-circulation, good biocompatibility, and physiologic barriers cross ability. EVs derived from different donor cells inherit varying characteristics and functions from their original cells and are favorable to serve as vectors for diagnosing and treating various diseases. However, EVs nanotheranostics are still in their infancy because of their limited accumulation at lesion sites and compromised therapy efficiency. Hence, engineering modification of EVs is usually needed to further enhance their stability, biological activity, and lesion-targeting capacity. Herein, we overview the characteristics of EVs from different sources, as well as the latest developments of surface engineering and cargo loading methods. We also focus especially on advances in EVs-based disease theranostics. At the end of the review, we predict the obstacles and prospects of the future clinical application of EVs.

Ultrashort Peptide Theranostic Nanoparticles by Microfluidic-Assisted Rapid Solvent Exchange.

Ultrashort peptides (USPs), composed of three to seven amino acids, can self-assemble into nanofibers in pure water. Here, using hydrodynamic focusing and a solvent exchange method on a microfluidic setup, we convert these nanofibers into globular nanoparticles with excellent dimensional control and polydispersity. Thanks to USP nanocarriers' structure, different drugs can be loaded. We used Curcumin as a model drug to evaluate the performance of USP nanocarriers as a novel drug delivery vehicle. These nanoparticles can efficiently cross the cell membrane and possess nonlinear optical properties. Therefore, we envisage USP nanoparticles as promising future theranostic nanocarriers.

NIR multiphoton ablation of cancer cells, fluorescence quenching and cellular uptake of dansyl-glutathione-coated gold nanoparticles.

Theranostics based on two-photon excitation of therapeutics in the NIR region is an emerging and powerful tool in cancer therapy since this radiation deeply penetrates healthy biological tissues and produces selective cell death. Aggregates of gold nanoparticles coated with glutathione corona functionalized with the dansyl chromophore (a-DG-AuNPs) were synthesized and found efficient nanodevice for applications in photothermal therapy (PTT). Actually the nanoparticle aggregation enhances the quenching of radiative excitation and the consequent conversion into heat. The a-DG-AuNPs are readily internalized in Hep G2 where the chromophore acts as both antenna and transducer of the NIR radiation under two-photons excitation, determining efficient cell ablation via photothermal effect.

Theranostic Gastrointestinal Endoscopy: Bringing Healing Light to the Lumen.

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.

Protein-Carbon Dot Nanohybrid-Based Early Blood-Brain Barrier Damage Theranostics.

For effective treatment of ischemic cerebral thrombosis, it is of great significance to find a facile way in assessing the early damage of blood-brain barrier (BBB) after ischemic stroke during thrombolysis by integrating thrombolytic agents with fluorescent materials. Herein, a novel type of protein-carbon dot  nanohybrids is reported by the incorporation of carbon dots on thrombolytic agents through covalent linkage. Both in vitro and ex vivo fluorescence imaging measurements have demonstrated remarkable imaging effects in the brain of transient middle cerebral artery occlusion mice. Besides, the outstanding thrombolytic capacity of the nanohybrids was determined by in vitro thrombolysis tests. As one of the few reports of the construction of thrombolytic agents and fluorescent nanomaterials, the nanohybrids retain thrombolysis ability and fluorescent traceability simultaneously. It may provide a promising indicator for early BBB damage and thrombolytic agent distribution to estimate the possibility of symptomatic intracranial hemorrhage after thrombolysis and supply tissue window evidence for clinical thrombolytic agent application.

Preclinical Evaluation of 203/212Pb-Labeled Low-Molecular-Weight Compounds for Targeted Radiopharmaceutical Therapy of Prostate Cancer.

Targeted radiopharmaceutical therapy (TRT) using α-particle radiation is a promising approach for treating both large and micrometastatic lesions. We developed prostate-specific membrane antigen (PSMA)-targeted low-molecular-weight agents for 212Pb-based TRT of patients with prostate cancer (PC) by evaluating the matching γ-emitting surrogate, 203Pb. Methods: Five rationally designed low-molecular-weight ligands (L1-L5) were synthesized using the lysine-urea-glutamate scaffold, and PSMA inhibition constants were determined. Tissue biodistribution and SPECT/CT imaging of 203Pb-L1-203Pb-L5 were performed on mice bearing PSMA(+) PC3 PIP and PSMA(-) PC3 flu flank xenografts. The absorbed radiation dose of the corresponding 212Pb-labeled analogs was determined using the biodistribution data. Antitumor efficacy of 212Pb-L2 was evaluated in PSMA(+) PC3 PIP and PSMA(-) PC3 flu tumor models and in the PSMA(+) luciferase-expressing micrometastatic model. 212Pb-L2 was also evaluated for dose-escalated, long-term toxicity. Results: All new ligands were obtained in high yield and purity. PSMA inhibitory activities ranged from 0.10 to 17 nM. 203Pb-L1-203Pb-L5 were synthesized in high radiochemical yield and specific activity. Whole-body clearance of 203Pb-L1-203Pb-L5 was fast. The absorbed dose coefficients (mGy/kBq) of the tumor and kidneys were highest for 203Pb-L5 (31.0, 15.2) and lowest for 203Pb-L2 (8.0, 4.2). The tumor-to-kidney absorbed dose ratio was higher for 203Pb-L3 (3.2) and 203Pb-L4 (3.6) than for the other agents, but with lower tumor-to-blood ratios. PSMA(+) tumor lesions were visualized through SPECT/CT as early as 0.5 h after injection. A proof-of-concept therapy study with a single administration of 212Pb-L2 demonstrated dose-dependent inhibition of tumor growth in the PSMA(+) flank tumor model. 212Pb-L2 also demonstrated an increased survival benefit in the micrometastatic model compared with 177Lu-PSMA-617. Long-term toxicity studies in healthy, immunocompetent CD-1 mice revealed kidney as the dose-limiting organ. Conclusion:203Pb-L1-203Pb-L5 demonstrated favorable pharmacokinetics for 212Pb-based TRT. The antitumor efficacy of 212Pb-L2 supports the corresponding 203Pb/212Pb theranostic pair for PSMA-based α-particle TRT in advanced PC.

Photochemical /Photocytotoxicity Studies of New Tetrapyrrolic Structures as Potential Candidates for Cancer Theranostics.

BACKGROUND: Detailed photochemical and photocytotoxicity studies of two new porphyrins: 5,10,15,20-meso-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5-(4-hydroxy-3- methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P2.2) are reported, as potential candidates for theranostics. For powdered samples of P2.1 and P2.2 adsorbed onto a powdered biocompatible substrate, polyethylene glycol (PEG), a concentration study was performed, correlating the fluorescence emission intensity with sample absorption to determine the useful concentration range for photodynamic therapy of cancer (PDT) in which aggregation does not occur. Cytotoxicity studies were performed in dark and illuminated conditions. METHODS: The laser induced luminescence set-up is home-made, a N2 laser is used as the excitation source and a time gated charged-coupled device (ICCD) as the detector. Fluorescence lifetime determinations were made using pulsed light sources from the excitation LEDs and measures of the fluorescence intensities at different time delays after the excitation pulse. The singlet oxygen formation quantum yields ΦΔ measurements were obtained by comparing the total area of the emission spectra for the reference compound and also for the samples under study in the same solvent and with the same optical density at the excitation wavelength (405 nm). An integrating sphere for relative and absolute measurements was used in this work as an alternative methodology to obtain the values for the fluorescence emission quantum yields (ΦF) of the adsorbed porphyrin under study. The cytotoxicity evaluation was made in the dark and under irradiation, using four different human tumor cell lines and one non-tumor primary cell culture. RESULTS: In order to establish the useful range of concentrations of the sensitizer for PDT, and due to the use of powdered samples, a special methodology was needed: the variations of the fluorescence lifetimes and fluorescence quantum yields were evaluated as a function of the concentration of the dye, measured by (1-R)*fdye. Both ΦF and τF are constant in the range from 0.002 to about 0.050 µmol g-1, and only after that a concentration quenching effect becomes visible, decreasing both ΦF and τF. This methodology is based in the correlations established between the Remission Function values and ΦF and τF obtained for increasing values of the sensitizer concentrations. CONCLUSIONS: The study of the aggregation effects of P2.1 and P2.2 porphyrins into a PEG matrix allowed us to determine the usable concentration range for photodynamic therapy use, where the aggregation of porphyrins decreases, therefore reducing the PDT action. The use of an integrating sphere for relative and absolute measurements of fluorescence quantum yields and also the lifetime studies as a function of the dye loading confirms the useful range for the use of P2.1 and P2.2 in PEG as powdered samples. The determination of the GI50, the porphyrin concentration which inhibits 50% of the cell growth, evidences that P2.2, the A3B porphyrin overtakes P2.1 (the A4 porphyrin) in terms of PDT efficiency and both porphyrins are much better PDT agents than the unsubstituted porphyrin, TPP. These data clearly show that porphyrins P2.2 and P2.1 exhibit an excellent behaviour in terms of its photocytotoxicity. These results encourage us to pursuit in the study of this family of porphyrins in which a balance of hydrophobic versus hydrophilic substituents in the phenyl group was achieved.

A Tumor Microenvironment-Responsive Biodegradable Mesoporous Nanosystem for Anti-Inflammation and Cancer Theranostics.

A nanoplatform that integrates diagnostic and therapeutic functions with intrinsic tumor microenvironment-responsive biodegradability is highly desired. Herein, a biodegradable nanotheranostic agent based on hollow mesoporous organosilica nanoparticles (HMONs), followed by encapsulating of heat shock protein 90 (Hsp 90) inhibitor is described. Then, the pore-engineering including gating with bovine serum albumin-iridium oxide nanoparticles (BSA-IrO2 ) and conjugation of polyethylene glycol (PEG) is conducted to yield 17AAG@HMONs-BSA-IrO2 -PEG (AHBIP) nanotheranostics for multimode computed tomography (CT)/photoacoustic (PA) imaging-guided photodynamic therapy (PDT) and low-temperature photothermal therapy (PTT). Such nanoplatforms show extraordinary photothermal conversion efficiency, high cargo loading (35.4% for 17AAG), and stimuli-responsive release of 17AAG for inhibition of Hsp90, which induces cell apoptosis at low-temperatures (≈41 °C). Also, the IrO2 simultaneously endows the nanotheranostics with catalytic activity in triggering the decomposition of H2 O2 into O2 and thus reducing the tumor hypoxia, as well as protecting normal tissues against H2 O2 -induced inflammation. AHBIP shows good photocatalysis activity for PDT as a result of the generation of superoxide anion by laser irradiation. The resulting AHBIP-mediated synergistic PTT/PDT offers an outstanding therapeutic outcome both in vitro and in vivo. Overall, the incorporation of the BSA-IrO2 and biodegradable HMONs into one nanoplatform has great potential for clinical applications.

Adaptive in vivo device for theranostics of inflammation: Real-time monitoring of interferon-γ and aspirin.

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist among cytokines, inflammation, and the innate and adaptive immune responses in maintaining homeostasis, health, and well-being. On-demand, local delivery of anti-inflammatory drugs to target tissues provides an approach for more effective drug dosing while reducing the adverse effects of systemic drug delivery. This work demonstrates a proof-of-concept theranostic approach for inflammation based on analyte-kissing induced signaling, whereby a drug (in this report, aspirin) can be released upon the detection of a target level of a proinflammatory cytokine (i.e., interferon-γ (IFN-γ)) in real time. The structure-switching aptamer-based biosensor described here is capable of quantitatively and dynamically detecting IFN-γ both in vitro and in vivo with a sensitivity of 10 pg mL-1. Moreover, the released aspirin triggered by the immunoregulatory cytokine IFN-γ is able to inhibit inflammation in a rat model, and the release of aspirin can be quantitatively controlled. The data reported here provide a new and promising strategy for the in vivo detection of proinflammatory cytokines and the subsequent therapeutic delivery of anti-inflammatory molecules. This universal theranostic platform is expected to have great potential for patient-specific personalized medicine. STATEMENT OF SIGNIFICANCE: We developed an adaptive in vivo sensing device whereby a drug, aspirin, can be released upon the detection of a proinflammatory cytokine, interferon-γ (IFN-γ), in real time with a sensitivity of 10 pg mL-1. Moreover, the aspirin triggered by IFN-γ depressed inflammation in the rat model and was delivered indirectly through blood and cerebrospinal fluid or directly to the inflammation tissue or organ without adverse gastrointestinal effects observed in the liver and kidney. We envision that, for the first time, patients with chronic inflammatory disease can receive the right intervention and treatment at the right time. Additionally, this technology may empower patients to monitor their personalized health and disease management program, allowing real-time diagnostics, disease monitoring, and precise and effective treatments.

Polymeric Hybrid Nanomicelles for Cancer Theranostics: An Efficient and Precise Anticancer Strategy for the Codelivery of Doxorubicin/miR-34a and Magnetic Resonance Imaging.

To realize precise tumor therapy, a versatile oncotherapy nanoplatform integrating both diagnostic and therapeutic functions is necessary. Herein, we fabricated a hybrid micelle (HM) utilizing two amphiphilic diblock copolymers, polyethylenimine-polycaprolactone (PEI-PCL) and diethylenetriaminepentaacetic acid gadolinium(III)  (Gd-DTPA)-conjugated polyethyleneglycol-polycaprolactone (Gd-PEG-PCL), to codeliver the small-molecule chemotherapy drugs doxorubicin (Dox) and microRNA-34a (miR-34a), denoted as Gd-HM-Dox/34a. Conjugating Gd-DTPA on the surface of hybrid micelles, leading the relaxation rate of Gd-DTPA increased more than 1.4 times (13.6 mM-1 S-1). Furthermore, hybrid micelles enhanced the ability of miR-34a to escape from lysosomes/endosomes and Dox release to the nucleus. In addition, the released miR-34a subsequently downregulates Bcl-2, cyclin D1, CDK6, and Bax expression and inhibits proliferation and migration of MDA-MB-231 breast cancer cells. Moreover, the suitable micelle size improved the penetration of Dox into three-dimensional (3D) multicellular spheroids compared with Gd-HM-Dox and Free Dox, generating efficient cell killing in the 3D multicellular spheroids. Furthermore, the Gd-HM-Dox/34a exhibited augmented accumulation in the tumor tissue, which improved the magnetic resonance (MR) imaging contrast of solid tumors and enhanced the combined efficiency of chemotherapeutic drugs Dox and therapeutic gene miR-34a in suppressing tumor growth on MDA-MB-231 tumor-bearing mice. Therefore, we established a hybrid micelle to offer a promising theranostic approach that inhibits tumor growth and enhances MR imaging.

Engineering pH-Responsive BODIPY Nanoparticles for Tumor Selective Multimodal Imaging and Phototherapy.

It is a challenge to develop multifunctional theranostic agents in one molecule, which simultaneously possesses tumor imaging ability with a high signal-to-noise ratio and excellent therapeutic activity. In this work, we synthesized and screened a series of BODIPY (BDP) with various absorption and fluorescence. The interplay of the molecular structure, pH-sensitive absorption and emission, and photodynamic and photothermal activities was well studied in detail. Photoinduced electron transfer, intramolecular charge transfer, and heavy atom effect were leveraged to engineer BDP with tumor imaging and therapeutic functions. The BDP nanoparticle formulations possessed multifunctional biological features, including selective treatment of cancer cells, near-infrared fluorescence, photoacoustic and computed tomography imaging, and photodynamic and photothermal therapy, as validated by cellular and animal experiments. These results not only give a new horizon to multifunctional BDP for biological applications but also show a new way to design the organic dye for tumor imaging and phototherapy.

Biodegradable Hollow MoSe2/Fe3O4 Nanospheres as the Photodynamic Therapy-Enhanced Agent for Multimode CT/MR/IR Imaging and Synergistic Antitumor Therapy.

Photodynamic therapy (PDT) is considered as one of the most effective cancer treatment strategies because of its minimally invasive and high efficiency. On account of the correlation between PDT and photocatalytic oxidation, the hollow MoSe2/Fe3O4 (MF-2) nanoheterostructure was constructed to enhance PDT as shown in this paper. The size and the hollow structure can be well controlled by the addition of F-127. MoSe2/Fe3O4 reveals the twofold reactive oxygen species (ROS) generation in contrast to the pure MoSe2, which is ascribed to the effective separation of photogenic charges. The novel hollow structure also supplies a lot of cavities for perfluorocarbon (PFC) and O2 loading, and O2@PFC@MF-2 can effectively overcome the hypoxic microenvironment to further cause more than 3 times ROS production. Moreover, the narrow band gap and hollow structure also make sure that the strong near-infrared (NIR) light absorption and high photothermal conversion efficiency is as high as 66.2%. Furthermore, the combination of Fe3O4 can further accelerate the effective biodegradation capacity of MF-2 because of the repeated endogenous redox reaction to form water-soluble MoVI-oxide species. Meanwhile, doxorubicin (Dox, anticancer drug) was assembled onto the MF-2@PEG nanomaterials through π-π staking and electrostatic interaction for chemotherapy. O2@PFC@MF-2@PEG/Dox possesses the potential application in triple-model computed tomography, magnetic resonance, and infrared (CT/MR/IR) imaging-guided photothermal/photodynamic/chemotherapy (PTT/PDT/chemotherapy) nanodiagnosis platforms.

Mn-Porphyrin-Based Metal-Organic Framework with High Longitudinal Relaxivity for Magnetic Resonance Imaging Guidance and Oxygen Self-Supplementing Photodynamic Therapy.

A nanoplatform for magnetic resonance imaging guidance and oxygen self-supplementing photodynamic therapy (PDT) was constructed on the basis of a porous metal-organic framework (PCN-222(Mn)), which was built by simple Mn-porphyrin ligands and biocompatible Zr4+ ions. Because of the good dispersibility of Mn3+ in the open framework and the high water affinity of the channel, PCN-222(Mn) exhibits a high longitudinal relaxivity of ∼35.3 mM-1 s-1 (1.0 T). In addition, it shows good catalytic activity for the conversion of endogenous hydrogen peroxide into oxygen, thereby improving tumor hypoxia during photodynamic therapy. The intravenous injection of PCN-222(Mn) into tumor-bearing mice mode provided good T1-weighted contrast of the tumor site and effectively inhibited tumor growth upon a single-laser irradiation. The findings provide insights for the development of multifunctional theranostic nanoplatforms based on simple components.

Smartphone controlled interactive portable device for theranostics in vitro.

In this work, a smartphone controlled interactive theranostic device has been developed to perform in vitro photodynamic therapy (PDT) and diagnostic assays for treatment assessment on a single platform. Further, silver nanorod (Ag NR) was identified as a photosensitizer and its effect was studied in three different cell lines. PDT was achieved with Ag NRs using low irradiation (1.4 mW/cm2 at 632 nm) from light emitting diodes (LEDs) in the device. Specifically, PDT in conjugation with widely used chemotherapeutic drug doxorubicin (Dox) proved effective in killing of HeLa cancer cells and multicellular tumor spheroids at a minimum dose of Ag (2.5 µg/mL). The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays performed with the device indicated the therapeutic success of the delivered PDT. The device is portable and can be adapted for different wavelength irradiations and radiation doses. Additionally, wireless operation using a custom designed smartphone application makes it convenient to use in complex environments without much of human intervention.

Two-photon AIE luminogen labeled multifunctional polymeric micelles for theranostics.

Intelligent polymeric micelles with fluorescence imaging feature have been emerged as promising tools for theranostics. However, conventional fluorescent dyes are limited by short wavelength excitation, interference of tissue autofluorescence, limited imaging depth and quenched emission in aggregation state. Methods: We synthesized a novel mPEG-SS-Poly (AEMA-co-TBIS) (mPEATss) copolymer to develop multifunctional polymeric micelles with great AIE feature for cancer therapy and AIE active two-photon bioimaging. The stimuli-responsive behavior and AIE active two-photon cell and tissue imaging as well as in vitro and in vivo antitumor ability of DOX-loaded mPEATss were studied. Results: mPEATss micelles showed excellent AIE active two-photon cell imaging ability and deep tissue imaging ability. Antitumor drug DOX could be encapsulated to form a drug-loaded micellar system with a small diameter of 65 nm. The disassembly and charge-conversion of mPEATss micelles could be triggered by acidic environment, resulting in accelerated drug release and great antitumor efficacy. In vivo, ex vivo imaging and in vivo pharmacokinetic study demonstrated that mPEATss micelles could efficiently accumulate in tumor sites, which ensured ideal anticancer effect. Conclusions: This pH and redox dual responsive and AIE active two-photon imaging polymeric micelles would be a promising candidate for theranostics.