Application of tumor-targeting peptide-decorated polypeptide nanoparticles with doxorubicin to treat osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core-shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion.

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.

Use of multifunctional composite nanofibers for photothermalchemotherapy to treat cervical cancer in mice.

A locally administered combination of chemotherapy and photothermal therapy may be suitable for the treatment of cervical cancer. In this study, doxorubicin (DOX) and indocyanine green (ICG) co-loaded mesoporous silica nanoparticles (DIMSN) were prepared. Then the nanoparticles were incorporated into chitosan/poly(vinyl alcohol) (CS/PVA) to form multifunctional composite nanofibers (DIMSN/F) via the electrospinning process. Under the mimic erosion of vaginal secretion, DIMSN/F presented site-specific drug release while the local delivery of a thermosensitive DIMSN-loaded gel (DIMSN/gel) failed in doing so. The vaginal implantation of DIMSN/F could achieve maximized drug accumulation in the vagina of mice compared to the systematic injection of DIMSN. Finally, the photothermalchemotherapy (PTCT) effects of DIMSN/F were studied in both subcutaneous and orthotopic cervical cancer models in mice but drug penetration in the hard nodular tumor posed a great challenge. For all this, the tumor inhibition rate (TIR) for orthotopic cervical/vaginal cancer was still as high as 72.5%, presenting its great potential for the treatment of cervical cancer.

Targeted delivery of 20(S)-ginsenoside Rg3-based polypeptide nanoparticles to treat colon cancer.

Colorectal cancer (CRC) is a major malignancy characterized by a high metastasis rate. Systematic chemotherapy is important for patients with advanced CRC. However, many limitations (e.g., side effects to normal organs, shorter circulation time, and unsatisfactory tumor inhibition results) of traditional chemotherapy restrict its further application. Thus, it is necessary to find a method to overcome these challenges and improve the efficacy of CRC treatment. In this study, 20(S)-ginsenoside (Rg3) co-loaded poly(ethylene glycol)-block-poly(L-glutamic acid-co-L-phenylalanine) (mPEG-b-P(Glu-co-Phe)) nanoparticles (Rg3-NPs) were prepared. mPEG-b-P(Glu-co-Phe)-based drug delivery systems are pH sensitive that can target cancer cells and circulate for longer in blood. Rg3 could be released rapidly from the nanoparticles within tumor cells. A subcutaneous colon cancer mouse model was developed to evaluate the anticancer efficiency of the Rg3-NPs. The in vivo study indicated that the Rg3-NPs could significantly inhibit tumor proliferation by decreasing the expressions of proliferating cell nuclear antigen, resulting in tumor apoptosis through the increased expressions of caspase-3. Our study demonstrated the marked potential of the Rg3-NPs to treat CRC.

The effects of irreversible electroporation on the stomach wall after ablating hepatic tissues.

This study aimed to evaluate the effect of irreversible electroporation (IRE) on the stomach wall after IRE was applied on liver tissues adjacent to the anterior wall of the stomach. IRE ablation was performed in eight Tibet mini-pigs with three lesions per pig. The IRE electrodes were inserted into the liver tissues situated close to the anterior wall of the stomach. As for the control group, the IRE electrodes were also inserted into the liver tissues for three lesions in four Tibet mini-pigs but did not turn on the current. Serum aminotransferase and WBC levels clearly increased in all the IRE ablated animals by Day 1 and decreased gradually thereafter. The gross postmortem examination at 7 days post-IRE revealed a whitish lesion with sharp demarcation on the serosal surface of the stomach, but we could not find any signs of ablation or just find a small, slightly reddish lesion at the Day-28 examination. On the Day-7 histopathological examination, inflammation and fibrosis were observed in the serosal layer of the stomach in each animal and mild inflammation of the myofibers was found in only two pigs. All the stomach layers returned to normalcy by 28 days post-IRE. Thus, IRE ablation of hepatic tissues situated close to the stomach wall cannot lead to stomach perforation. IRE is therefore a safe procedure for ablating hepatic tumors that are adjacent to the stomach.

Combination therapy comprising irreversible electroporation and hydroxycamptothecin loaded electrospun membranes to treat rabbit VX2 subcutaneous cancer.

Irreversible electroporation (IRE) is a kind of promising cancer treatment technology. However, local recurrence still occurs because of incomplete ablation. The aim of this study was to investigate the combined therapy of IRE and a hydroxycamptothecin loaded electrospun membrane (EM/HCPT) to treat rabbit VX2 subcutaneous cancer. HCPT loaded membranes were developed by electrospinning. Mechanical test and in vitro drug release study of EM/HCPT were performed. 24 rabbits with subcutaneous VX2 tumor were randomly divided into four groups: the control group, the EM/HCPT group, the IRE ablation group, and the IRE + EM/HCPT group. The tumor cells were ablated by IRE first, followed by subcutaneous implantation of EM/HCPT to release HCPT constantly in order to damage the residual cancer cells. The tumor inhibition efficacy was assessed by the tumor real-time monitoring, histological and immunofluorescent analyses, and transmission electron microscopy (TEM) examination. Assessment of the release from EM/HCPT showed that HCPT release lasted for about 7 days. The in vivo antitumor efficacy assessment, histological and immunofluorescent analyses, and TEM examination showed that IRE + EM/HCPT had the best tumor inhibition ability. In addition, the biochemical analyses and hematoxylin and eosin (H&E) staining of normal organs indicated that IRE + EM/HCPT treatment was safe. Our study provided a new concept in cancer treatment and might promote the application of IRE.