Gas-generating mesoporous silica nanoparticles with rapid localized drug release for enhanced chemophotothermal tumor therapy.

Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO2 gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.

Can high-frequency ultrasound combined computed tomography accurately diagnose thyroid tumor?: A protocol of systematic review and meta-analysis.

BACKGROUND: Previous clinical studies have reported that clinical value of high-frequency ultrasound combined computed tomography (HFUCT) is used for diagnosis of thyroid tumor (TT). However, no study has investigated this topic systematically. Therefore, this study will evaluate the clinical value of HFUCT for the diagnosis of TT. METHODS: We will search the databases of Cochrane Library, EMBASE, PUBMED, SCOPUS, Web of Science, OpenGrey, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure from any time period published to the present. We will consider all case-controlled studies that assessed the clinical value of HFUCT for diagnosis of TT. Two authors will independently scan titles and abstracts to check eligible studies, followed by full-text read. We will extract data and assess study quality using Quality Assessment of Diagnostic Accuracy Studies tool. RevMan 5.3 software will be utilized for data pooling and statistical analysis. RESULTS: This study will be performed to assess the clinical value of HFUCT for the diagnosis of TT, and will provide an evidence-based synthesis for clinical application and further study. CONCLUSION: Summary of this study will provide the latest evidence to determine whether HFUCT can be used for TT diagnosis accurately. STUDY REGISTRATION: INPLASY202040022.

A Dual-Model Imaging Theragnostic System Based on Mesoporous Silica Nanoparticles for Enhanced Cancer Phototherapy.

Mesoporous silica nanoparticles (MSNs) show great promise to be exploited as versatile multifunctional nanocarriers for effective cancer diagnosis and treatment. In this work, perfluorohexane (PFH)-encapsulated MSNs with indocyanine green (ICG)-polydopamine (PDA) layer and poly(ethylene glycol)-folic acid coating (designated as MSNs-PFH@PDA-ICG-PEG-FA) are successfully fabricated to achieve tumor ultrasonic (US)/near-infrared fluorescence (NIRF) imaging as well as photothermal therapy (PTT)/photodynamic therapy (PDT). MSNs-PFH@PDA-ICG-PEG-FA exhibits good monodispersity with high ICG loading, significantly enhances ICG photostability, and greatly improves cellular uptake. Upon single 808 nm NIR irradiation, the nanocarrier not only efficiently generates hyperthermia to realize PTT, but also produces reactive oxygen species (ROS) for effective PDT. Meanwhile, NIR irradiation can trigger PFH to undergo vaporization and provide a super-resolution US image. Thus, the PTT/PDT combination therapy can be dually guided by PFH-induced US imaging and ICG-induced NIRF imaging. In vivo antitumor studies demonstrate that PTT/PDT from MSNs-PFH@PDA-ICG-PEG-FA significantly inhibits tumor growth and achieves a cure rate of 60% (three out of five mice are completely cured). Hence, the multifunctional MSNs appear to be a promising theragnostic nanoplatform for multimodal cancer imaging and therapy.

Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy.

The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

Dual pH/reduction-responsive hybrid polymeric micelles for targeted chemo-photothermal combination therapy.

The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.

A multifunctional nanoplatform for cancer chemo-photothermal synergistic therapy and overcoming multidrug resistance.

The integration of various therapy strategies into a single nanoplatform for synergistic cancer treatment has presented a great prospect. Herein, docetaxel (DTX)-loaded poly lactic-co-glycolic acid (PLGA)-coated polydopamine modified with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was synthesized for chemo-photothermal synergistic therapy against cancer. Firstly, the DTX-loaded PLGA NPs were prepared by a facile and robust nanoprecipitation method. Then, they were coated with dopamine to achieve the photothermal effects and to be further modified with TPGS, which can inhibit the P-glycoprotein-mediated multidrug resistance (MDR). The near-infrared (NIR) laser irradiation triggered DTX release from DTX-loaded PLGA NPs@PDA-TPGS, and then the chemo-photothermal therapy effect could be enhanced. The in vitro experimental results illustrated that DTX-loaded PLGA NPs@PDA-TPGS exhibits excellent photothermal conservation properties and remarkable cell-killing efficiency. In vivo antitumor studies further confirmed that DTX-loaded PLGA NPs@PDA-TPGS could present an outstanding synergistic antitumor efficacy compared with any monotherapy. This work exhibits a novel nanoplatform, which could not only load chemotherapy drugs efficiently, but could also improve the therapeutic effect of chemotherapy drugs by overcoming MDR and light-mediated photothermal cancer therapy.