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Background: The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake., Results: Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 10 6 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy., Conclusions: This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies., (© 2021. The Author(s).)

Magnetite (Fe 3 O 4 ) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH-CDT synergistic therapy based only on a single component of Fe 3 O 4 still remains a challenge. Herein, hollow Fe 3 O 4 mesocrystals (MCs) are constructed via a modified solvothermal method. Owing to the distinctive magnetic property of the mesocrystalline structure, Fe 3 O 4 MCs show excellent magnetothermal conversion efficiency with a specific absorption rate of 722 w g -1 at a Fe concentration of 0.6 mg mL -1 , much higher than that of Fe 3 O 4 polycrystals (PCs). Moreover, Fe 3 O 4 MCs also exhibit higher peroxidase-like activity than Fe 3 O 4 PCs, which may be ascribed to the higher ratio of Fe 2+ /Fe 3+ and more oxygen defects in the Fe 3 O 4 MCs. Detailed in vivo results confirm that Fe 3 O 4 MCs can instantly initiate CDT by producing the detrimental • OH, and such boosted reactive oxygen levels not only induces cell apoptosis but also reduces the expression of heat shock proteins, thus enabling low-temperature-mediated MH. More importantly, the in situ rising temperature resulted from MH in turn facilitates CDT, thus achieving a self-augmented synergistic effect between MH and CDT.

Purpose: To investigate the killing effect of photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) on human breast cancer MCF7 and MDA-MB-231 cells in vitro., Methods: MCF7 and MDA-MB-231 breast cancer cells cultured in vitro were incubated with calcitriol (concentration of 10-8M, 10-10 M, 10-12 M, 10-14 M, 10-16 M, 0 M) to determine a proper concentration. The cells were divided into experimental group (calcitriol, HPD group and laser), HPD group (HPD and laser), calcitriol group (calcitriol and laser), blank laser group (laser alone) and blank group (no drugs and laser). Then the cells were preconditioned with calcitriol for 48 hrs and incubated with HPD for 6 hrs. After light exposure with 630 nm laser, the cells' viability and the reactive oxygen species (ROS) were assessed. After 8 hrs, flow cytometry was applied to detect the rate of cell apoptosis. The fluorescence intensity in cells was detected. Furthermore, the expression of porphyrin synthetic enzymes in pretreated breast cancer cells was analyzed., Results: MTT assay showed that the viability of cells in the experimental group was lowest (p<0.05). The ROS intensity of the experimental group was higher (p<0.01). The rate of cell apoptosis was higher in the experimental group (p<0.05), and the fluorescence of the experimental group was higher (p<0.01). Furthermore, mechanistic studies documented that the expression of the porphyrin synthesis enzyme coproporphyrinogen oxidase (CPOX) was increased by calcitriol at the mRNA level., Conclusion: This research revealed a simple, non-toxic and highly effective preconditioning regimen to selectively enhance protoporphyrin IX (PpIX) fluorescence and the response of HPD-PDT in breast cancer search. This finding suggests that the combined treatment of breast cancer cells with calcitriol plus HPD may provide an effective and selective therapeutic modality to enhance HPD-induced PpIX fluorescent quality for improving discrimination of tumor tissue and PDT efficacy.

High-intensity focused ultrasound (HIFU) is deemed to be a promising noninvasive therapeutic modality for cancers as well as non-neoplastic diseases. However, the accuracy of the technique in the diagnosis and treatment of tumors remains unsatisfactory. HIFU, when combined with multifunctional synergistic agents (SAs), has the potential to be of greater diagnostic and therapeutic efficacy. Here we describe a smart and multifunctional hollow mesoporous Prussian blue (HMPBs) theranostic nanoplatform, the hollow structure of which is capable of encapsulating doxorubicin (DOX) and perfluorohexane (HMPBs-DOX/PFH). In vitro and in vivo studies validated that HMPBs-DOX/PFH can be used as an amplifiable dual-mode imaging contrast agent, which can simultaneously enhance ultrasound (US) and photoacoustic (PA) imaging for guiding and monitoring tumor therapy. When exposed to HIFU, this versatile HMPBs-DOX/PFH agent could increase the cavitation effect and use lower HIFU intensity to achieve coagulative necrosis. Furthermore, it significantly accelerated the release of DOX thereby enhancing chemotherapeutic efficacy and avoiding systemic side effects of the drug. Such a novel theranostic nanoplatform is expected to integrate dual-mode guided imaging with greater therapeutic efficacy and fewer side effects and is very promising for the noninvasive synergistic tumor therapy.

Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm(2)) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc-1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers.

The synergistic effect of chemotherapy and ablation using high-intensity focused ultrasound (HIFU) is realized with a newly developed drug-delivery system. The system comprises an ultrathin silica shell surrounding a poly(lactic-co-glycolic acid) nanoemulsion core containing the drug (CPT) and a perfluorocarbon (PFOB). This nanosystem presents many advantages in drug delivery, such as excellent structural stability, high drug-loading capacity, and rapid HIFU-mediated drug release., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Backgrounds: Sonodynamic therapy (SDT) as an emerging reactive oxygen species (ROS)-mediated antitumor strategy is challenged by the rapid depletion of oxygen, as well as the hypoxic tumor microenvironment. Instead of the presently available coping strategies that amplify the endogenous O2 level, we have proposed a biodegradable O2 economizer to reduce expenditure for augmenting SDT efficacy in the present study. Results: We successfully fabricated the O2 economizer (HMME@HMONs-3BP-PEG, HHBP) via conjugation of respiration inhibitor 3-bromopyruvate (3BP) with hollow mesoporous organosilica nanoparticles (HMONs), followed by the loading of organic sonosensitizers (hematoporphyrin monomethyl ether; HMME) and further surface modification of poly(ethylene glycol) (PEG). The engineered HHBP features controllable pH/GSH/US-sensitive drug release. The exposed 3BP could effectively inhibit cell respiration for restraining the oxygen consumption, which could alleviate the tumor hypoxia conditions. More interestingly, it could exorbitantly elevate the autophagy level, which in turn induced excessive activation of autophagy for promoting the therapeutic efficacy. As a result, when accompanied with suppressing O2-consumption and triggering pro-death autophagy strategy, the HHBP could achieve the remarkable antitumor activity, which was systematically validated both in vivo and in vitro assays. Conclusions: This work not only provides a reduce expenditure means for enduring SDT, but also represents an inquisitive strategy for tumor treatments by inducing pro-death autophagy. [ABSTRACT FROM AUTHOR]

The precise delivery and controllable release of carbon monoxide (CO) to tumor tissues is an emerging anticancer therapy because CO in a high dose can be detrimental to cell survival and tumor growth. However, CO gas therapy is limited by the gaseous nature of CO that hinders its enrichment and controllable release to tumor tissues. Here, a novel photodynamic therapy (PDT)‐driven CO controllable release system (CORM@G3DSP‐Ce6) that integrates the photosensitizer chlorin e6 (Ce6) and H2O2‐sensitive CO releasing molecule CORM‐401 into peptide dendrimer‐based nanogels (G3DSP) is described. Upon excitation with near‐infrared light, Ce6‐mediated photochemical effect not only promotes the efficient cellular internalization of CORM@G3DSP‐Ce6, but also triggers the rapid intracellular CO release from CORM‐401 by depleting the H2O2 produced during PDT. Importantly, the PDT‐driven CO release does not impair the generation capability of singlet oxygen (1O2). As a result, accompanied with the simultaneous generation of large amounts of 1O2 and CO in cells, the combination of PDT and CO gas therapy offers significant synergistic anticancer effects and superior therapeutic safety both in vitro and in vivo. A photodynamic therapy (PDT)‐driven carbon monoxide (CO) controllable release system is developed for PDT+CO synergistic anticancer therapy. With near‐infrared light excitation, this system not only exhibits efficient cellular internalization but also triggers rapid intracellular CO release by depleting H2O2 produced during PDT, without impairing singlet oxygen generation. Significant synergistic anticancer effects with superior biosafety are achieved both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe 3 O 4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe 3 O 4 @PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe 3 O 4 @PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe 3 O 4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe 3 O 4 @PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe 3 O 4 @PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe 3 O 4 @PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment. • Developed a multifunctional bone cement (DOX/Fe 3 O 4 @PMMA) • Determined the drug release properties of DOX/Fe 3 O 4 @PMMA • Provided a minimally invasive modality for removal of osteosarcoma • Explored the synergistic magnetically induced ablation and the chemotherapy of osteosarcoma [ABSTRACT FROM AUTHOR]