Dual-driven nanomotors enable tumor penetration and hypoxia alleviation for calcium overload-photo-immunotherapy against colorectal cancer.

The treatment efficacies of conventional medications against colorectal cancer (CRC) are restricted by a low penetrative, hypoxic, and immunosuppressive tumor microenvironment. To address these restrictions, we developed an innovative antitumor platform that employs calcium overload-phototherapy using mitochondrial N770-conjugated mesoporous silica nanoparticles loaded with CaO2 (CaO2-N770@MSNs). A loading level of 14.0 wt% for CaO2-N770@MSNs was measured, constituting an adequate therapeutic dosage. With the combination of oxygen generated from CaO2 and hyperthermia under near-infrared irradiation, CaO2-N770@MSNs penetrated through the dense mucus, accumulated in the colorectal tumor tissues, and inhibited tumor cell growth through endoplasmic reticulum stress and mitochondrial damage. The combination of calcium overload and phototherapy revealed high therapeutic efficacy against orthotopic colorectal tumors, alleviated the immunosuppressive microenvironment, elevated the abundance of beneficial microorganisms (e.g., Lactobacillaceae and Lachnospiraceae), and decreased harmful microorganisms (e.g., Bacteroidaceae and Muribaculaceae). Moreover, together with immune checkpoint blocker (αPD-L1), these nanoparticles showed an ability to eradicate both orthotopic and distant tumors, while potentiating systemic antitumor immunity. This treatment platform (CaO2-N770@MSNs plus αPD-L1) open a new horizon of synergistic treatment against hypoxic CRC with high killing power and safety.

Near-Infrared-Enpowered Nanomotor-Mediated Targeted Chemotherapy and Mitochondrial Phototherapy to Boost Systematic Antitumor Immunity.

Phototherapy is an important strategy to inhibit tumor growth and activate antitumor immunity. However, the effect of photothermal/photodynamic therapy (PTT/PDT) is restricted by limited tumor penetration depth and unsatisfactory potentiation of antitumor immunity. Here, a near-infrared (NIR)-driven nanomotor is constructed with a mesoporous silicon nanoparticle (MSN) as the core, end-capped with Antheraea pernyi silk fibroin (ApSF) comprising arginine-glycine-aspartate (RGD) tripeptides. Upon NIR irradiation, the resulting ApSF-coated MSNs (DIMs) loading with photosensitizers (ICG derivatives, IDs) and chemotherapeutic drugs (doxorubicin, Dox) can efficiently penetrate into the internal tumor tissues and achieve effective phototherapy. Combined with chemotherapy, a triple-modal treatment (PTT, PDT, and chemotherapy) approach is developed to induce the immunogenic cell death of tumor cells and to accelerate the release of damage-associated molecular patterns. In vivo results suggest that DIMs can promote the maturation of dendritic cells and surge the number of infiltrated immune cells. Meanwhile, DIMs can polarize macrophages from M2 to M1 phenotypes and reduce the percentages of immunosuppressive Tregs, which reverse the immunosuppressive tumor microenvironment and activate systemic antitumor immunity. By achieving synergistic effects on the tumor inhibition and the antitumor immunity activation, DIMs show great promise as new nanoplatforms to treat metastatic breast cancer.

Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy.

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin (DOX)-loaded silk fibroin-based nanoparticles (NPs) with surface functionalization by photosensitizer (N770). The obtained nanotheranostics (N770-DOX@NPs) had desirable particle size (157 nm) and negative surface charge (-25 mV). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli (acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared (NIR) fluorescence imaging, photothermal imaging, and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumor retardation effect among all treatment groups based on tumor-bearing mouse models and a patient-derived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imaging-guided mitochondrial phototherapy (photothermal therapy and photodynamic therapy) and chemotherapy. Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

Retrospective study of therapeutic effect of Tongbi paste vs Fufangzhuifeng paste for shoulder periarthritis.

OBJECTIVE: To compare the therapeutic effects of Tongbi and Fufangzhuifeng pastes in shoulder periarthritis. METHODS: The retrospective study was conducted at the Chongqing Traditional Chinese Medicine Hospital, China, and comprised data of shoulder periarthritis patients who were treated from December 2018 to June 2019. Group A had data of patients treated with Tongbi paste and group B had data of patients treated with Fufangzhuifeng paste. The groups were compared for effect on pain, shoulder flexion, abduction and extension. Data was analysed using SPSS 22. RESULTS: Of the 81 patients, 43(53%) were in group A; 18(42%) males and 25(58%) females with an overall mean age of 54.26±12.38 years (range: 28-79 years) who were suffering from shoulder periarthritis for a mean duration of 5.08±3.07 months (range: 0.25-13 months). There were 38(47%) patients in group B; 23(60.5%) females and 15(39.5%) males with an overall mean age of 53.08±11.08 years (range: 33-76 years) who were suffering from shoulder periarthritis for a mean duration of 4.96±2.77 months (range: 1-12 months). Mean pain, shoulder flexion, abduction and extension scores after two weeks of treatment were significantly better for group A compared to group B (p<0.001), but after three weeks of treatment, intergroup differences were different but not significant (p>0.05). CONCLUSION: Tongbi and Fufangzhuifeng pastes were found to have a positive effect in the treatment of shoulder periarthritis, with the former providing faster relief.

The efficacy and safety of fire needle for the treatment of lumbar disc herniation: A protocol for systematic review and meta-analysis.

BACKGROUND: A very large acceleration in clinical studies on the efficacy of fire needle to treat lumbar disc herniation (LDH) are increasing, while studies on the assessment of its efficacy are still lacking. Therefore, this study will demonstrate the efficacy of fire needle in the treatment of LDH combining with the meta-analysis. METHODS: The studies on randomized controlled trials (RCTs) will be searched at the databases of China National Knowledge Infrastructure (CNKI), WANFANG database (Chinese Medicine Premier), Chinese Scientific Journal Database (VIP), Chinese Biomedical Literature database (CBM), PubMed, EMBASE, and Cochrane Library from their inception to May 1, 2020. RESULTS: This authentic and multi-dimensional study will shed light on the referable information for the treatment of LDH with fire needle. CONCLUSION: This study will evaluate the efficacy of fire needle in the treatment of LDH. REGISTRATION: PROSPERO (registration number CRD42020158596).