RESUMEN
Macrophages have high plasticity and heterogeneity, and can suppress or mediate inflammation, depending on their cytokine secretion and phenotype. Regulating macrophage polarization into its M2 phenotype has a remarkable effect on inflammatory inhibition, inducing the regeneration of injured tissues. Here, we synthesized two heptamannosylated ß-cyclodextrin derivatives (CD-Man7 and C3-CD-Man7) and demonstrated that their multivalent mannose ligands could induce M2 macrophage polarization to accelerate wound healing. Unlike hydrophilic CD-Man7, amphiphilic C3-CD-Man7 can self-assemble to form nanoparticles (CD-Man-NPs) in aqueous solution. Further, in vitro results confirmed that multivalent mannose ligands of either CD-Man7 or CD-Man-NPs stimulated RAW264.7 macrophages to differentiate into the M2 phenotype, which promoted fibroblast migration via a paracrine mechanism. In vivo results confirmed that both CD-Man7 and CD-Man-NPs reduced the inflammatory response in wound tissue and accelerated wound healing. The present study demonstrates multivalent effects of CD-Man7 and CD-Man-NPs on M2 macrophage polarization, indicating the therapeutic potential of these ß-cyclodextrin glycoconjugates in the treatment of inflammatory diseases and wound healing.
Asunto(s)
Cicatrización de Heridas , beta-Ciclodextrinas , Citocinas , Humanos , Activación de Macrófagos , MacrófagosRESUMEN
The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) has emerged as a promising strategy for complete tumor ablation therapy. Herein, a boron dipyrromethene (BODIPY)-conjugated hyaluronic acid polymer that can self-assemble to form the nanoparticles (BODIPY-HA NPs) was prepared for combined cancer PDT and PTT. The fluorescence emission and reactive oxygen species (ROS) generation of BODIPY-HA NPs were inhibited because of the π-π stacking behavior of BODIPY, resulting in photothermal effect under 808 nm light irradiation. Upon the internalization by cancer cells, the BODIPY-HA NPs could disassemble into BODIPY-HA molecules, with the recovery of the fluorescence and ROS generation for PDT. Importantly, in vitro results confirmed that combined PTT and PDT have exhibited better anticancer effect than PTT alone upon 808 nm laser irradiation. These results showed that the self-assembled BODIPY-HA NPs may be a promising nanomedicine for synergistic cancer PDT and PTT.
Asunto(s)
Nanopartículas , Fotoquimioterapia , Boro , Línea Celular Tumoral , Ácido Hialurónico , Terapia Fototérmica , Porfobilinógeno/análogos & derivadosRESUMEN
The development of activatable photosensitizers (PSs) is of particular interest for achieving tumor photodynamic therapy (PDT) with minimal side effects. However, the in vivo applications of PSs are limited by complex physiological and biological delivery barriers. Herein, boron dipyrromethene (BDP)-based nanoparticles are developed through the self-assembly of a multifunctional "one-for-all" building block for enhanced tumor penetration and activatable PDT. The nanoparticles show excellent colloidal stability and long circulation lifetime in blood. Once they reach the tumor site, the first-stage size reduction occurs due to the hydrolysis of the Schiff base bond between polyethylene glycol and the cyclic Arg-Gly-Asp peptide in the acidic tumor microenvironment (pH~6.5), facilitating tumor penetration and specific recognition by cancer cells overexpressing integrin ανß3 receptors. Upon the endocytosis by cancer cells, the second-stage size reduction is triggered by more acidic pH in lysosomes (pH~4.5). Importantly, the protonated diethylamino groups can block photoinduced electron transfer from the amine donor to the excited PSs and accelerate complete disassembly of the nanoparticles into single PS molecule, with the recovery of the fluorescence and photoactivity for efficient PDT. This study presents a smart PS delivery strategy involving acidity-triggered hierarchical disassembly from the nano to molecular scale for precise tumor PDT.
Asunto(s)
Nanopartículas , Fotoquimioterapia , Boro , Línea Celular Tumoral , Fármacos Fotosensibilizantes , Porfobilinógeno/análogos & derivadosRESUMEN
OBJECTIVES: To compare the mechanical and sutured ureteroneocystostomy in a canine model. METHODS: In 18 dogs, extravesical ureteroneocystostomy on 1 side was randomly assigned to end-to-side anastomosis performed with a titanium ring-pin stapler or interrupted absorbable sutures. To create the antireflux tunnel, the longitudinal line of the muscle layer was closed over the implanted ureter with titanium clips or sutures. At 3 months postoperatively, renal ultrasonography, intravenous urography, ascending cystography, the Whitaker test, and the macroscopic and microscopic results were assessed. RESULTS: The ureteroneocystostomy with the ring pin stapler and the antireflux tunnel construction with titanium clips had a 100% technical success rate. Compared with manual suturing anastomosis, the suture-free technique took a significantly shorter time and resulted in slightly, but not significantly, less ureteral obstruction after 3 months. One dog in group 2 had evidence of ureteral dilation and hydronephrosis compared with the normal contralateral side. No signs of stone formation, urinary cyst, or fistulas were found after either closure method. None of the 18 dogs demonstrated vesicoureteral reflux. Histologic examination showed no signs of acute inflammation or marked fibrosis in any of the 18 specimens. Moreover, the intrapelvic pressure in group 1 was approximately similar to that of the normal contralateral side. CONCLUSIONS: Ureteroneocystostomy performed with a titanium ring-pin stapler is feasible and faster than using conventional sutures. This suture-free technique is simple and safe, with possibly lower complication rates than a nonstented suture technique. Additional studies with a longer follow-up duration are needed to confirm these results.
Asunto(s)
Cistostomía/métodos , Engrapadoras Quirúrgicas , Suturas , Uréter/cirugía , Animales , Perros , Diseño de Equipo , Masculino , Derivación Urinaria/métodosRESUMEN
BACKGROUND & OBJECTIVE: Intravesical instillation is an important adjuvant therapy on preventing postoperative recurrence of superficial bladder transitional cell carcinoma, but the recurrence rate is still high. This study was to evaluate the prophylactic effect of intravesical instillation of hydroxycamptothecin (HYD) plus bacillus Calmette-Guerin (BCG) on postoperative recurrence of bladder transitional cell cancer. METHODS: A total of 45 bladder cancer patients who underwent TURBT or partial cystectomy were divided into two groups: 24 patients in combination group received single intravesical instillation of HYD in Week 1 after operation and regular intravesical instillation of BCG since Week 2; 21 patients in BCG group received regular intravesical instillation of BCG since Week 1 after operation. All the patients were followed up for 24 months. RESULTS: Three patients had recurrence at 2, 10, and 12 months after operation individually in BCG group; no recurrence developed in combination group. The recurrence rate was significantly higher in BCG group than in combination group (14.28% vs. 0, P<0.05). No serious adverse events and complication developed in both groups. CONCLUSION: Early use of single intravesical instillation of HYD plus subsequent regular intravesical instillation of BCG is markedly effective for preventing postoperative recurrence of bladder transitional cell cancer, with few adverse events.