Improving the efficacy of melanoma treatment remains an important global challenge. Here, we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2) based immunotherapy in an effort to address this challenge. Short-hairpin RNA (shRNA) targeting Ptpn2 was coencapsulated with doxorubicin (DOX) in the cell membrane of M1 macrophages (M1HD@RPR). The prepared nanoparticles (NPs) were effectively phagocytosed by B16F10 cells and M1 macrophages, but not by M0 macrophages. Hence, NP evasion from the reticuloendothelial system (RES) was improved and NP enrichment in tumor sites increased. M1HD@RPR can directly kill tumor cells and stimulate immunogenic cell death (ICD) by DOX and downregulate Ptpn2. It can promote M1 macrophage polarization and dendritic cell maturation and increase the proportion of CD8+ T cells. M1HD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor cells without harming the surrounding tissue. These findings establish M1HD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.
Erlotinib (ERT), oral administration agents, is one of the most pivotal targeted drugs in the treatment of non-small cell lung cancer (NSCLC); however, its poor solubility, low oral bioavailability, and capricious toxicity limit broader clinical applications. In this paper, a novel injectable matrix is prepared based on hollow mesoporous silica nanoparticles (HMSNs) and thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PDLLA-PEG-PDLLA, PLEL) hydrogel to encapsulate and localize the sustained release of ERT for improved efficacy against NSCLC. The test-tube-inversion method shows that this ERT-loaded hydrogel composite (ERT@HMSNs/gel) presents as an injectable flowing solution under room temperature and transfers into a physically crosslinked non-flowing gel structure at physiological temperature.The ERT@HMSNs/gel composite shows a much longer intratumoral and peritumoral drug retention by in vivo imaging study. Notably, this injectable drug delivery system (DDS) provides an impressive balance between antitumor efficacy and systemic safety in a mice xenograft model. The novel ERT loaded HMSNs/gel system may be a promising candidate for the in situ treatment of NSCLC. Moreover, this study provides a prospective platform for the design and fabrication of a nano-scaled delivery system for localized anticancer therapies.
Polypropylene (PP) composites that contain silver micro-particles (MILLION KILLER, denoted as Ag-Ms) and conductive carbon black (CB) have both antibacterial and antistatic properties. In the present study, the antibacterial and antistatic PP/Ag-Ms/CB composites were prepared by melt blending. The results showed that when the content was 0.8 wt%, Ag-Ms could be uniformly dispersed in the PP matrix and the mechanical properties of the composites remained stable. And the reduction percentages of Staphylococcus aureus and Escherichia coli were more than 80% which showed the good antibacterial behavior. In addition, conductive carbon black had reinforcing and toughening effects on the mechanical properties of PP/Ag-Ms/CB composites. When the content of CB was beyond 30 wt%, the surface resistance of the composite was reduced to less than 108 Ω which showed a remarkable antistatic property. According to the different filling content of conductive carbon black, it can flexibly regulate the resistivity of PP, and the conductive effect is durable and stable. We thus can produce permanent antistatic materials.
Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.