Intelligent protein-coated bismuth sulfide and manganese oxide nanocomposites obtained by biomineralization for multimodal imaging-guided enhanced tumor therapy.

Radiotherapy (RT) has been used clinically to overcome cancer in recent decades. However, the abnormal tumor microenvironment (TME), involving hypoxia, acidosis and a dense extracellular matrix, is found to be related to the resistance of tumors to RT. Herein, intelligent bovine serum albumin (BSA)-coated Bi2S3 and MnO2 (Bi2S3-MnO2) nanocomposites synthesized via biomineralization are capable of modulating the hypoxic TME effectively to enhance the efficacy of RT. After intravenous injection, the BSA-Bi2S3-MnO2 nanocomposites show efficient accumulation in tumors, where endogenous H2O2 can react with MnO2 to generate oxygen in situ, leading to increased tumor oxygenation to overcome the hypoxia-associated resistance to RT. Moreover, the photothermal effect induced by the BSA-Bi2S3-MnO2 nanocomposites further relieves hypoxia in the TME and, finally, synergistically improves the effects of RT. In this work, we present a simple strategy to fabricate intelligent therapeutic nanoparticles to improve therapeutic efficiency towards cervical cancer.

Specific cell targeting with APRPG conjugated PEG-PLGA nanoparticles for treating ovarian cancer.

Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG-PLA and mPEG-PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.