Nanomaterial-Based Antivascular Therapy in the Multimodal Treatment of Cancer.

Abnormal tumor vasculature and a hypoxic tumor microenvironment (TME) limit the effectiveness of conventional cancer treatment. Recent studies have shown that antivascular strategies that focus on antagonizing the hypoxic TME and promoting vessel normalization effectively synergize to increase the antitumor efficacy of conventional therapeutic regimens. By integrating multiple therapeutic agents, well-designed nanomaterials exhibit great advantages in achieving higher drug delivery efficiency and can be used as multimodal therapy with reduced systemic toxicity. In this review, strategies for the nanomaterial-based administration of antivascular therapy combined with other common tumor treatments, including immunotherapy, chemotherapy, phototherapy, radiotherapy, and interventional therapy, are summarized. In particular, the administration of intravascular therapy and other therapies with the use of versatile nanodrugs is also described. This review provides a reference for the development of multifunctional nanotheranostic platforms for effective antivascular therapy in combined anticancer treatments.

Co-delivery of NIR-II semiconducting polymer and pH-sensitive doxorubicin-conjugated prodrug for photothermal/chemotherapy.

Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm2 for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo. Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. STATEMENT OF SIGNIFICANCE: Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo.

Protective effects of Paederia scandens extract on rheumatoid arthritis mouse model by modulating gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Paederia scandens (Lour.) Merr. (P. scandens) has been traditionally used to treat the pain of rheumatism. AIM OF THE STUDY: The purpose of this study was to investigate the possible influences of P. scandens on the progression of rheumatoid arthritis (RA), inflammatory responses and gut bacterial communities in RA mouse model. MATERIALS AND METHODS: collagen-induced arthritis (CIA) mice were orally administered with P. scandens extract (PSE) for 24 days. Then, pro-inflammatory cytokine levels in the serum were measured, and gut microbiota was examined with Illumina HiSeq. RESULTS: Compared with the vehicle group, PSE significantly inhibited paw swelling and reduced arthritis score. Histological examination of ankle soft tissue of demonstrated PSE effectively inhibited the tissue fibrosis and inflammatory cell infiltration. The increased serum levels of TNF-α, IL-1ß, IL-6, IL-7, and IL-23 in RA mice were significantly suppressed by PSE. Moreover, PSE treatment help restore gut microbial ecosystem altered in RA mice including decreasing relative abundance of inflammatory related microorganisms, Desulfovibrio, Mucispirillum, Helicobacter, and Lachnospiraceae. CONCLUSION: These results suggest that PSE has therapeutic effects in RA mice with CIA, showing the potential as anti-arthritis reagent.

Effect of cervus and cucumis peptides on osteoblast activity and fracture healing in osteoporotic bone.

Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.

[Molluscicidal activity of methanol extracts of Jatropha curcas leaves against Ampullaria gigas].

OBJECTIVE: To evaluate the molluscicidal activities of methanol extract of Jatropha curcas leaves against Ampullaria gigas. METHODS: Young snails, adult snails and eggs of Ampullaria gigas were treated with the methanol extract of J. curcas leaves at different doses for different time lengths and the molluscicidal effects of the extract were evaluated. RESULTS: The methanol extract showed a significant molluscicidal effect on the young snails at a low concentration, and treatment with 75 mg/L extract for more than 3 days resulted in a 100% mortality rate of the young snails. The Jatropha leaf methanol extract also showed toxicity to adult snails and eggs. CONCLUSION: Jatropha leaves have a great potential for developing green pesticides to control Ampullaria gigas, but its biochemical mechanism needs further research.