Long-circulation zwitterionic dendrimer nanodrugs for phototherapy of tumors.

The development of stealth and effective antitumor nanodrugs has been drawing great attention. Herein, generation five poly(amide amine) dendrimer (G5 PAMAM) was modified by zwitterionic material carboxybetaine methacrylamide (CBMAA) on its surface to prepare zwitterionic dendrimer (G5-CBMAAn). The results showed that G5-CBMAA30 had the longest blood circulation time due to its thickest zwitterionic layer, and its residual rate after injection into mice at 2 and 12 h was as high as 47.22 % and 14.37 %, respectively. Nanodrug G5-CBMAA30-ICG was prepared by containing indocyanine green (ICG) in the cavity of G5-CBMAA30. G5-CBMAA30-ICG had better tumor targeting ability and antitumor effect than free ICG in mice after laser irradiation, and the tumor inhibition rate was 96.6 % after 14 days' treatment. The prepared G5-CBMAA30-ICG has great potential applications in the field of antitumor by phototherapy.

PD1 blockade potentiates the therapeutic efficacy of photothermally-activated and MRI-guided low temperature-sensitive magnetoliposomes.

This study investigates the effect of PD1 blockade on the therapeutic efficacy of novel doxorubicin-loaded temperature-sensitive liposomes. Herein, we report photothermally-activated, low temperature-sensitive magnetoliposomes (mLTSL) for efficient drug delivery and magnetic resonance imaging (MRI). The mLTSL were prepared by embedding small nitrodopamine palmitate (NDPM)-coated iron oxide nanoparticles (IO NPs) in the lipid bilayer of low temperature-sensitive liposomes (LTSL), using lipid film hydration and extrusion. Doxorubicin (DOX)-loaded mLTSL were characterized using dynamic light scattering, differential scanning calorimetry, electron microscopy, spectrofluorimetry, and atomic absorption spectroscopy. Photothermal experiments using 808 nm laser irradiation were conducted. In vitro photothermal DOX release studies and cytotoxicity was assessed using flow cytometry and resazurin viability assay, respectively. In vivo DOX release and tumor accumulation of mLTSL(DOX) were assessed using fluorescence and MR imaging, respectively. Finally, the therapeutic efficacy of PD1 blockade in combination with photothermally-activated mLTSL(DOX) in CT26-tumor model was evaluated by monitoring tumor growth, cytokine release and immune cell infiltration in the tumor tissue. Interestingly, efficient photothermal heating was obtained by varying the IO NPs content and the laser power, where on-demand burst DOX release was achievable in vitro and in vivo. Moreover, our mLTSL exhibited promising MR imaging properties with high transverse r2 relaxivity (333 mM-1 s-1), resulting in superior MR imaging in vivo. Furthermore, mLTSL(DOX) therapeutic efficacy was potentiated in combination with anti-PD1 mAb, resulting in a significant reduction in CT26 tumor growth via immune cell activation. Our study highlights the potential of combining PD1 blockade with mLTSL(DOX), where the latter could facilitate chemo/photothermal therapy and MRI-guided drug delivery.

Encapsulated doxorubicin crystals influence lysolipid temperature-sensitive liposomes release and therapeutic efficacy in vitro and in vivo.

Doxorubicin (DOX)-loaded lysolipid temperature-sensitive liposomes (LTSLs) are a promising stimuli-responsive drug delivery system that rapidly releases DOX in response to mild hyperthermia (HT). This study investigates the influence of loaded DOX crystals on the thermosensitivity of LTSLs and their therapeutic efficacy in vitro and in vivo. The properties of DOX crystals were manipulated using different remote loading methods (namely (NH4)2SO4, NH4-EDTA and MnSO4) and varying the lipid:DOX weight ratio during the loading step. Our results demonstrated that (NH4)2SO4 or NH4-EDTA remote loading methods had a comparable encapsulation efficiency (EE%) into LTSLs in contrast to the low DOX EE% obtained using the metal complexation method. Cryogenic transmission electron microscopy (cryo-TEM) revealed key differences in the nature of DOX crystals formed inside LTSLs based on the loading buffer or/and the lipid:DOX ratio used, resulting in different DOX release profiles in response to mild HT. The in vitro assessment of DOX release/uptake in CT26 and PC-3 cells revealed that the use of a high lipid:DOX ratio exhibited a fast and controlled release profile in combination with mild HT, which correlated well with their cytotoxicity studies. Similarly, in vivo DOX release, tumour growth inhibition and mice survival rates were influenced by the physicochemical properties of LTSLs payload. This study demonstrates, for the first time, that the characteristics of DOX crystals loaded into LTSLs, and their conformational rearrangement during HT, are important factors that impact the TSLs performance in vivo.

Synthesis of gold nanoflowers stabilized with amphiphilic daptomycin for enhanced photothermal antitumor and antibacterial effects.

The development of effective agents for cancer therapy and inhibition of bacterial infection has drawn a great deal of interest. Photothermal therapy has been widely used for the thermal ablation of tumor cells. In addition, antibiotics have the ability to inhibit the growth of bacteria. Thus, the combination of photothermal therapy and antibiotics may be one of the methods to address the problem. Herein, it is the first time that daptomycin (Dap) micelles were used as the template and reducing agents to prepare stable daptomycin-gold nanoflowers (Dap-AunNFs) under mild conditions. The energy dispersive spectrometer (EDS) spectrum and X-ray diffraction (XRD) spectrum indicated that Dap-AunNFs were successfully prepared. When the molar ratio of HAuCl4 to Dap was 6, the gold nanoparticles inside of Dap-AunNFs were about 80 nm with flower-like shape. In addition, the photothermal conversion efficiency of Dap-Au6NFs was about 40%. More importantly, Dap-Au6NFs inhibited the growth of tumors and bacteria under the radiation of near-infrared light at 808 nm. The prepared Dap-Au6NFs could be used as photothermal antitumor and antibacterial agents in the future.

Green synthesis of palladium nanoparticles using lentinan for catalytic activity and biological applications.

The green synthesis of palladium nanoparticles (Pd NPs) for catalysis and biological applications has been gaining great interest. To replace complex plant extracts, lentinan (LNT) may be a good reducing and stabilizing agent. In this work, a simple and green method using LNT to reduce and stabilize palladium Pd NPs was verified. The resulting LNT stabilized palladium nanoparticles (Pd n -LNT NPs) were characterized by UV-Vis spectroscopy, DLS, TEM, and XPS. The results indicated that Pd NPs inside of Pd n -LNT NPs had a small size (2.35-3.32 nm). Pd n -LNT NPs were stable in solution for 7 days. In addition, Pd n -LNT NPs had higher catalytic activity towards the reduction of 4-nitrophenol than other catalysts. More importantly, Pd n -LNT NPs had negligible cytotoxicity towards cells and showed good antioxidant activity. Taken together, the prepared Pd n -LNT NPs have great potential bio-related applications.