ABSTRACT
BACKGROUND: The combination of drug delivery with immune checkpoint targeting has been extensively studied in cancer therapy. However, the clinical benefit for patients from this strategy is still limited. B7 homolog 3 protein (B7-H3), also known as CD276 (B7-H3/CD276), is a promising therapeutic target for anti-cancer treatment. It is widely overexpressed on the surface of malignant cells and tumor vasculature, and its overexpression is associated with poor prognosis. Herein, we report B7H3 targeting doxorubicin (Dox)-conjugated gold nanocages (B7H3/Dox@GNCs) with pH-responsive drug release as a selective, precise, and synergistic chemotherapy-photothermal therapy agent against non-small-cell lung cancer (NSCLC). RESULTS: In vitro, B7H3/Dox@GNCs exhibited a responsive release of Dox in the tumor acidic microenvironment. We also demonstrated enhanced intracellular uptake, induced cell cycle arrest, and increased apoptosis in B7H3 overexpressing NSCLC cells. In xenograft tumor models, B7H3/Dox@GNCs exhibited tumor tissue targeting and sustained drug release in response to the acidic environment. Wherein they synchronously destroyed B7H3 positive tumor cells, tumor-associated vasculature, and stromal fibroblasts. CONCLUSION: This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Doxorubicin , Lung Neoplasms , Nanoparticles , Photothermal Therapy , Humans , B7 Antigens , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Drug Liberation , Gold , Hydrogen-Ion Concentration , Hyperthermia, Induced , Lung Neoplasms/drug therapy , Phototherapy , Photothermal Therapy/methods , Tumor Microenvironment , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Animals , Mice , Xenograft Model Antitumor AssaysABSTRACT
AIM: To summarize systematically our ten-year experience in non-surgical treatment of postoperative bile leakage, and explore its methods and indications. METHODS: The clinical data of 57 patients with postoperative bile leakage treated non-surgically from January 1991 to December 2000 were reviewed retrospectively. RESULTS: The site of the leakage was mainly the disrupted or damaged fistulous tracts of T tube in 25 patients (43.9 %), the fossae of gallbladder in 14 cases (24.6 %), the cut surface of liver in 7 cases(12.3 %), and it was undetectable in the other 2 cases. Besides bile leakage, the wrong ligation of bile ducts was found in 3 patients, residual stones of the distal bile duct in 5 patients, benign papillary strictures in 3, and biloma resulting from bile collections in 2. The diagnoses were made according to the history of surgery, clinical situation, abdominal paracentesis, ultrasonography, ERCP, PTC, MRI/MRCP, gastroscopy and percutaneous fistulography. All 57 patients were treated non-surgically at the beginning of bile leakage. The non-surgical methods included keeping original drainage unobstructed, percutaneous abdominal paracentesis or drainage, percutaneous transhepatic cholangial/biliary drainage (PTCD/PTBD),endoscopic management, traditional Chinese medicine and so on. Of the 57 patients,2 patients died,5 were converted to reoperation later, the other 50 were directly cured by non-surgical methods without any complication. The cure rate of the non-surgery was 82.5 %(50/57). CONCLUSION: Many nonoperative methods are available to treat postoperative bile leakage. Non-surgical treatment may serve as the first choice for the treatment of bile leakage for its advantages in higher cure rate, convenience and safety in practice. It is important to choose the specific non-surgical method according to the volume, site of bile leakage and patient's condition.