Developing nanomedicine with highly adaptive behaviors has shown great effectiveness in cancer treatment. However, the multi-functional integration of nano-therapeutic systems inevitably leads to complexity in the structure and impairs the operational efficiency or performance. Herein, we describe a novel nano-therapeutic system, G4-AB, capable of simultaneous dual conversions of the size and charge while targeting the acidic tumor microenvironment. G4-AB, containing a hydrophobic inner cavity for doxorubicin (DOX) loading, was synthesized by modifying amine-terminated 4th-generation polyamidoamine (G4-PAMAM) dendrimers with acylsulfonamide betaine (AB). Due to the dipole–dipole interaction among the AB moieties, G4-AB self-assembles to form micellar clusters with a zwitterionic surface. Possessing an anti-fouling property and suitable size, G4-AB exhibits optimized blood circulation under physiological pH conditions. Moreover, the extracellular pH value of the tumor microenvironment (pH 6.5) can trigger the protonation of acylsulfonamide, resulting in the cationization of AB and dissociation of G4-AB into unimolecular micelles (∼12 nm) due to electrostatic repulsion. The synergistic dual conversions further ensure drug accumulation with enhanced tumor penetration and cell internalization. The in vitro and in vivo experiments demonstrate that the G4-AB-DOX nano-therapeutic system possesses better antitumor efficiency and lower toxicity than free DOX or PEGylated PAMAM.
Xiao-He Liu,Yi He,Zhi Li,Ai-Hua Cheng,Zhiqi Song,Zhi-Xuan Yu,Shouning Chai,Cheng Cheng,Chi He
Recently, atomically precise metal nanoclusters (NCs) become a new class of photosensitizer for light energy conversion in metal-cluster-sensitized semiconductor (MCSS) system. However, fundamental understanding for the suitable combination of NCs and semiconductor is still unclear. Aside from aspects of light harvesting, energy level alignment and catalytic activity, interfacial interaction behavior at NCs/semiconductor interface is also crucial due to its important influence in charge transportation. In this work, the interface interaction between Au NCs and TiO 2 is examined by precise transformation of Au NCs from Au 22 (SG) 18 to Au 18 (SG) 14 , as well as its effect on photocatalytic hydrogen production activity. From the optical, charge transport and solid-states spectroscopy analyses, it is able to display that precisely tuning the number of core atoms from Au 22 (SG) 18 to Au 18 (SG) 14 results in the strong interface interaction between Au NCs and TiO 2 , reflecting in high difference of work function and modified surface band bending of TiO 2 , therefore promoting the injection of electrons from NCs to TiO 2 and reducing interfacial charges recombination. As a result, Au 18 (SG) 14 /TiO 2 shows higher hydrogen generation rate than Au 22 (SG) 18 /TiO 2 under light irradiation . This work would provide new insights into rational combination of metal NCs with semiconductor and highlights the overlooked effect of interfacial interaction behavior on light energy conversion.
Pancreatic ductal adenocarcinoma (PDAC), one of the most challenging cancers, is uniquely characterized by a biological barrier composed of multiple components in the extracellular matrix, preventing penetration of chemotherapeutic agents and hindering clinical drug treatment. Collagen I arrangement is critical. In this study, gemcitabine is chosen as the chemotherapeutic agent and dasatinib as the collagen-I-disrupting agent. When collagen I arrangement is disrupted, not only the chemotherapeutic drug enters the tumor area better, but the infiltration of CD8 + T cells into the tumor also increases. Therefore, a hypoxia-responsive linker-crosslinked polymer, DGD/L@GBI, is designed, which can be simultaneously loaded with two therapeutic agents, gemcitabine and dasatinib. The polymer is encapsulated by nucleic acid aptamers that target the PDAC stromal microenvironment and shield the surface. The aptamer is removed upon arrival at the PDAC hypoxic microenvironment, exposing the positively charged core to achieve charge reversal. Particle size transformation is achieved using linkers that respond to a hypoxic microenvironment. Increased intratumoral penetration is achieved using the dual transformation capabilities of the formulation. Pairing these two agents can result in a powerful efficacy in chemotherapy sensitization and immune infiltration.
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