Yuanyi Zheng

A Facile One‐Pot Synthesis of a Two‐Dimensional MoS2/Bi2S3 Composite Theranostic Nanosystem for Multi‐Modality Tumor Imaging and Therapy

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Manganese oxide-based multifunctionalized mesoporous silica nanoparticles for pH-responsive MRI, ultrasonography and circumvention of MDR in cancer cells

Nano-biotechnology has been introduced into cancer theranostics by engineering a new generation of highly versatile hybrid mesoporous composite nanocapsules (HMCNs) for manganese-based pH-responsive dynamic T(1)-weighted magnetic resonance imaging (MRI) to efficiently respond and detect the tumor acidic microenvironment, which was further integrated with ultrasonographic function based on the intrinsic unique hollow nanostructures of HMCNs for potentially in vitro and in vivo dual-modality cancer imaging. The manganese oxide-based multifunctionalization of hollow mesoporous silica nanoparticles was achieved by an in situ redox reaction using mesopores as the nanoreactors. Due to the dissolution nature of manganese oxide nanoparticles under weak acidic conditions, the relaxation rate r(1) of manganese-based mesoporous MRI-T(1) contrast agents (CAs) could reach 8.81 mM(-1)s(-1), which is a 11-fold magnitude increase compared to the neutral condition, and is almost two times higher than commercial Gd(III)-based complex agents. This is also the highest r(1) value ever reported for manganese oxide nanoparticles-based MRI-T(1) CAs. In addition, the hollow interiors and thin mesoporous silica shells endow HMCNs with the functions of CAs for efficient in vitro and in vivo ultrasonography under both harmonic- and B-modes. Importantly, the well-defined mesopores and large hollow interiors of HMCNs could encapsulate and deliver anticancer agents (doxorubicin) intracellularly to circumvent the multidrug resistance (MDR) of cancer cells and restore the anti-proliferative effect of drugs by nanoparticle-mediated endocytosis process, intracellular drug release and P-gp inhibition/ATP depletion in cancer cells.

Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation

Organic/inorganic, hybrid, multifunctional, material-based platforms combine the merits of diverse functionalities of inorganic nanoparticles and the excellent biocompatibility of organic systems. In this work, superparamagnetic poly(lactic-co-glycolic acid) (PLGA) microcapsules (Fe(3)O(4)/PLGA) have been developed, as a proof-of-concept, for the application in ultrasound/magnetic resonance dual-modality biological imaging and enhancing the therapeutic efficiency of high intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo. Hydrophobic Fe(3)O(4) nanoparticles were successfully integrated into PLGA microcapsules by a typical double emulsion evaporation process. In this process, highly dispersed superparamagnetic Fe(3)O(4)/PLGA composite microcapsules with well-defined spherical morphology were obtained with an average diameter of 885.6 nm. The potential of these microcapsules as dual contrast agents for ultrasonography and magnetic resonance imaging were demonstrated in vitro and, also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite microcapsules were administrated into rabbits bearing breast cancer model for the evaluation of the in vivo HIFU synergistic ablation efficiency caused by the introduction of such microcapsules. Our results showed that the employment of the composite microcapsules could efficiently enhance ultrasound imaging of cancer, and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition, pathological examination was systematically performed to detect the structural changes of the target tissue caused by HIFU ablation. This finding demonstrated that successful introduction of these superparamagnetic microcapsules into HIFU cancer surgery provided an alternative strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy of cancer.

Perfluorohexane-encapsulated mesoporous silica nanocapsules as enhancement agents for highly efficient high intensity focused ultrasound (HIFU).

An inorganic enhancement agent (EA) for high-intensity focused ultrasound (HIFU) imaging based on mesoporous silica nanocapsules is presented. The pronounced coagulative necrosis effects demonstrate, both in vitro and in vivo, that the EA can be developed as a highly promising theranostic agent for effective HIFU imaging and therapy owing to its high stability, efficient perfluorohexane loading and release, enhanced tumor ablation capability, and easy uptake by target tissues. Copyright

Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.

Current strategies for tumor-induced sentinel lymph node detection and metastasis therapy have limitations. In this work, we co-encapsulated iron oxide nanoparticles and chemotherapeutic drug into poly(lactic-co-glycolic acid) (PLGA) microbubbles to form multifunctional polymer microbubbles (MPMBs) for both tumor lymph node imaging and therapy. Fe(3)O(4) nanoparticles and doxorubicin (DOX) co-encapsulated PLGA microbubbles were prepared and filled with perfluorocarbon gas. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging and US triggered drug delivery were evaluated both in vitro and in vivo. The MPMBs exhibited characters like narrow size distribution and smooth surface with a mean diameter of 868.0 ± 68.73 nm. In addition, varying the concentration of Fe(3)O(4) nanoparticles in the bubbles did not significantly influence the DOX encapsulation efficiency or drug loading efficiency. Our in vitro results demonstrated that these MPMBs could enhance both US and MR imaging which was further validated in vivo showing that these MPMBs enhanced tumor lymph nodes signals. The anti-tumor effect of MPMBs mediated chemotherapy was assessed in vivo using end markers like tumor proliferation index, micro blood vessel density and micro lymphatic vessel density, which were shown consistently the lowest after the MPMBs plus sonication treatment compared to controls. In line with these findings, the tumor cell apoptotic index was found the largest after the MPMBs plus sonication treatment. In conclusion, we have successfully developed a doxorubicin loaded superparamagnetic PLGA-Iron Oxide multifunctional theranostic agent for dual-mode US/MR Imaging of lymph node, and for low frequency US triggered therapy of metastasis in lymph nodes, which might provide a strategy for the imaging and chemotherapy of primary tumor and their metastases.

Multifunctional mesoporous composite nanocapsules for highly efficient MRI-guided high-intensity focused ultrasound cancer surgery

Bloodless surgical knife: Nano-biotechnology has been introduced into imaging-guided high-intensity focused ultrasound (HIFU) cancer surgery by adopting engineered multifunctional manganese-based mesoporous composite nanocapsules as the contrast agents for T(1)-weighted magnetic resonance imaging (MRI) and simultaneously as synergistic agents for MRI-guided HIFU cancer surgery.

Injectable 2D MoS2‐Integrated Drug Delivering Implant for Highly Efficient NIR‐Triggered Synergistic Tumor Hyperthermia

MoS2 nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/MoS2 /DOX composite implant are successfully constructed based on the unique phase-changing behavior of PLGA/MoS2 /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS2 and DOX within tumors, and the integrated MoS2 and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.

Au-nanoparticle coated mesoporous silica nanocapsule-based multifunctional platform for ultrasound mediated imaging, cytoclasis and tumor ablation

Au nanoparticles-coated, perfluorohexane-encapsulated and PEGylated mesoporous silica nanocapsule-based enhancement agents (MSNC@Au-PFH-PEG, abb. as MAPP) have been synthesized, for the ultrasound-induced cytoclasis, contrast-intensified ultrasound (US) imaging and US-guided high intensity focused ultrasound (HIFU) surgical therapy. Both the US-induced thermal effect and US triggered release of loaded model drug with MAPP under US exposure indicated the excellent US sensitivity of MAPP and its applicability for the combined chemo-/thermal therapy and future potential for HIFU ablation; US imaging under different modes verify the attractive US contrast intensification by using MAPP; US-guided HIFU therapy ex vivo and in vivo with MAPP is found to be highly efficient on rabbit VX2 xenograft tumor ablation due to the high thermal energy accumulation and increased mechanical/thermal effects from US-induced PFH bubble cavitations. MAPP can be promisingly used as an inorganic theranostic platform for contrast-intensified US imaging, combined chemotherapy and efficient HIFU tumor ablation under the guidance by the intensified US.

A Prussian Blue‐Based Core–Shell Hollow‐Structured Mesoporous Nanoparticle as a Smart Theranostic Agent with Ultrahigh pH‐Responsive Longitudinal Relaxivity

Novel core-shell hollow mesoporous Prussian blue @ Mn-containing Prussian blue analogue (HMPB@MnPBA) nanoparticles, designated as HMPB-Mn) as an intelligent theranostic nanoagent, are successfully constructed by coating a similarly crystal-structured MnPBA onto HMPB. This can be used as a pH-responsive T1 -weighted magnetic resonance imaging contrast agent with ultrahigh longitudinal relaxivity (r1 = 7.43 m m(-1) s(-1) ), and achieves the real-time monitoring of drug release.

Ultrasound triggered drug release from 10-hydroxycamptothecin-loaded phospholipid microbubbles for targeted tumor therapy in mice.

Ultrasound targeted microbubble destruction (UTMD) was one of the most promising strategies to enhance drug delivery in cancer therapy. Microbubbles (MBs) serve as a vehicle to carry anti-tumor drugs and locally release them when exposed to therapeutic ultrasound, resulting in drug accumulation in tumor tissues and enhanced anti-tumor effect. However the ultrasound triggered drug delivery system has been seriously limited due to the poor loading capacity of MBs. Here we present a new strategy to overcome the low drug payload of MBs for ultrasound guided drug delivery. In this study, we developed a novel microbubble carrying 10-HCPT which only needs a particularly low single dose of injection (4-6 mg) for tumor therapy in clinical application, therefore, the required high dosing of drug loaded MBs for ultrasound mediated drug delivery is not necessary. We subsequently investigated the combination of ultrasound application with HLMs to achieve therapeutic effect on tumor at a feasible dose of MBs. HLMs were manufactured with a high drug encapsulation and loading content and simultaneously maintained the acoustic properties as an ultrasound contrast agent. After that, tumor-bearing mice were routinely and non-invasively administered with HLMs through the tail vein and were then exposed to ultrasound, resulting in a remarkable drug accumulation in tumor tissues and a significant increase in tumor inhibition rate (70.6%) compared with HLMs alone (47.8%) as well as commercial HCPT injection (49.4). In conclusion, HLMs are expected to improve the therapeutic efficacy of MBs and are worthy of further study for UTMD mediated drug delivery.