Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response

Objectives: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer.

Methods: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study.

Results: The final NP had a small size (around 120?nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8?±?1.1% and 99.5?±?0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs.

Conclusions: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.     

荧光光谱法研究桑色素与人血清白蛋白的相互作用

采用荧光猝灭光谱、紫外-可见吸收光谱研究了桑色素与人血清白蛋白(HSA)的结合作用。实验表明桑色素对HSA的荧光猝灭属于单一静态猝灭反应,在溶液中以摩尔比1:1牢固结合,各结合反应的平衡常数Kp>105,结合常数Kb>104;根据F rster非辐射能量转移机理,求算HSA与桑色素间距离r为3.81~3.58nm,能量转移效率E为0.18~0.13。并根据结合反应的热力学常数推测了药物与HSA之间的主要作用力类型为疏水作用力和偶极-偶极作用力。     

Effectiveness and biocompatibility of a novel biological adhesive application for repair of meniscal tear on the avascular zone

Abstract

We have investigated the effectiveness and safety of a newly developed biological adhesive for repair of meniscal tear. The adhesive was composed of disuccinimidyl tartrate (DST) as a crosslinker and human serum albumin (HSA) as a hardener. To determine adequate concentration, bonding strength was measured using a tensiometer 5 min after applying the adhesive on the avascular zone tear of porcine meniscus; it was compared with the strengths of commercially available cyanoacrylate-based and fibrin-based adhesives. In vivo examination was performed using Japanese white rabbits, creating longitudinal tears on the avascular zone of meniscus and applying DST–HSA adhesive. Three months after operation the rabbits were sacrificed and tension test and histological evaluation were performed. Bonding strength was measured in three porcine meniscus groups: (i) only suturing, (ii) suturing after applying the adhesive on surface and (iii) suturing using an adhesive-soaked suture. The optimum concentrations were 0.1 mmol of DST and 42 w/v% of HAS. Bonding strength was greatest with cyanoacrylate-based adhesive, followed by DST–HSA adhesive, and fibrin-based adhesive. No inflammation was observed in the synovium or surrounding tissues 3 months after using the DST–HSA adhesive. Bonding strength was greatest with DST–HSA adhesive-soaked suturing group (77 ± 6 N), followed by suturing only group (61 ± 5 N) and surface adhesive application group (60 ± 8 N). The newly developed DST-HSA adhesive is considered safe and may be effective in enforcement of bonding of avascular zone tear of the meniscus.     

自组装白蛋白共负载光敏剂及基因纳米递送系统的构建及初步评价

通过小分子十二烷基硫酸钠(SDS)调节牛血清白蛋白(BSA)疏水区域暴露,使白蛋白分子在不借助额外催化剂和交联剂的相对温和条件下自组装,合成了一种可共载光敏剂二氢卟吩e6(Ce6)及基因(CpG寡脱氧核苷酸)的白蛋白纳米载体。在其成功负载光敏剂Ce6后,用聚醚酰亚胺(PEI)对BSA纳米颗粒(BSA NP)表面进行了修饰,并通过调节合适的修饰比例得到高效负载基因的纳米体系。随后对纳米颗粒体系的形貌、尺寸分布、表面电荷、稳定性以及基因负载能力、产生活性氧能力进行了初步评估。结果表明合成得到的PEI修饰的白蛋白共负载Ce6及CpG(BSA-Ce6-PEI-CpG)的纳米颗粒尺寸分布均匀,微观形貌呈现光滑规整的圆球形,对CpG基因有较好的负载能力,并在光照下高效产生活性氧,且纳米体系能够在表面活性剂处理后依然保持结构稳定,可作为良好的光敏剂和基因递送载体。     

Effectiveness and biocompatibility of a novel biological adhesive application for repair of meniscal tear on the avascular zone

We have investigated the effectiveness and safety of a newly developed biological adhesive for repair of meniscal tear. The adhesive was composed of disuccinimidyl tartrate (DST) as a crosslinker and human serum albumin (HSA) as a hardener. To determine adequate concentration, bonding strength was measured using a tensiometer 5 min after applying the adhesive on the avascular zone tear of porcine meniscus; it was compared with the strengths of commercially available cyanoacrylate-based and fibrin-based adhesives. In vivo examination was performed using Japanese white rabbits, creating longitudinal tears on the avascular zone of meniscus and applying DST–HSA adhesive. Three months after operation the rabbits were sacrificed and tension test and histological evaluation were performed. Bonding strength was measured in three porcine meniscus groups: (i) only suturing, (ii) suturing after applying the adhesive on surface and (iii) suturing using an adhesive-soaked suture. The optimum concentrations were 0.1 mmol of DST and 42 w/v% of HAS. Bonding strength was greatest with cyanoacrylate-based adhesive, followed by DST–HSA adhesive, and fibrin-based adhesive. No inflammation was observed in the synovium or surrounding tissues 3 months after using the DST–HSA adhesive. Bonding strength was greatest with DST–HSA adhesive-soaked suturing group (77 ± 6 N), followed by suturing only group (61 ± 5 N) and surface adhesive application group (60 ± 8 N). The newly developed DST-HSA adhesive is considered safe and may be effective in enforcement of bonding of avascular zone tear of the meniscus.     

汽巴蓝功能微球对人血清白蛋白的吸附性能研究

通过分散共聚制得了聚苯乙烯接枝聚醋酸乙烯酯(PSt-g-PVAc)微球,粒径控制在500～700nm之间.在碱性条件下将PSt-g-PVAc微球表面的PVAc链醇解为聚乙烯醇(PVA),得到了PSt-g-PVA微球,提高了其在水中的分散稳定性.使汽巴蓝(CB)与PSt-g-PVA表面的羟基进行亲核反应,制得了CB作为配体的新型吸附剂汽巴蓝功能微球(CB微球),元素分析测得CB微球表面的CB最大含量为139.22μmol/g,探讨了其在不同人血清白蛋白(HSA)浓度、pH值和吸附时间下对HSA的吸附性能.当HSA浓度为1.0mg/mL、pH为5.14时,CB微球对HSA的最大吸附量为40.9mg/g,并分析了CB微球与HSA的相互作用机理.由NaSCN进行解吸试验,发现可将吸附在CB微球上的HSA解吸92.11%以上,且CB微球的重复使用性能良好.     

硅掺杂羟基磷灰石生物活性微粉对人血清白蛋白的吸附特性

对含硅羟基磷灰石(Si-HA)与人血清白蛋白(HSA)的吸附特性及动力学特征进行了研究,计算了表观活化能,用等温吸附曲线进行拟合。结果表明,该吸附属于Langmuir型。Si-HA和HA吸附HSA的表观活化能分别为21.28和35.57 kJ.mol-1,20℃下吸附反应的速率常数分别为1.48和1.34 min-1,饱和吸附量分别为25.34和21.34 mg.g-1,Si-HA具有比纯HA更好的吸附优势。通过XRD、FTIR及荧光光谱分析,探讨了HSA在Si-HA和HA表面的吸附作用机制,表明Si-HA与蛋白表面吸附反应是以化学吸附为主、包含物理吸附的混合吸附过程。从分子结构的角度揭示了Si-HA和HA吸附蛋白质性能的差异,为进一步探讨Si-HA和HA生物相容性提供了新途径。     

Effects of green-, yellow- and red-emitting CdTe QDs on the interaction between 7-hydroxyflavone/quercetin with human serum albumin in vitro

In this study, 7-hydroxyflavone and quercetin were studied for their affinities for human serum albumin (HSA) in the presence and absence of quantum dots (QDs). Three typical CdTe QDs with maximum emissions of 535?nm (green-emitting, G-QDs), 598?nm (yellow-emitting, Y-QDs) and 654?nm (red-emitting, R-QDs) were tested. The fluorescence intensities of HSA decreased remarkably with addition of QDs. Quercetin resulted in obvious blue-shifts of the maximum λ _em of HSA from 340.8 to 332.6?nm and 7-hydroxyflavone hardly changed the maximum λ _em of HSA in the absence of QDs. The extents of shifts of the maximum λ _em of HSA induced by 7-hydroxyflavone or quercetin in the presence of QDs were larger than that in the absence of QDs. When 8.00?µmol/L of 7-hydroxyflavone was added, the fluorescence decreased by 68.1%, 65.7% and 71.8% in the presence of G-QDs, R-QDs and Y-GDs, respectively, from the original G-QDs, R-QDs and Y-GDs that resulted in 42%, 43% and 55%, respectively. When 8.00?µmol/L of quercetin was tested, the fluorescence decreased by 72.4%, 69.5% and 75.6% in the presence of G-QDs, R-QDs and Y-GDs, respectively. G- and R-QDs hardly affected the affinities of 7-hydroxyflavone and quercetin for HSA. However, Y-QDs decreased the affinities of 7-hydroxyflavone and quercetin for HSA by about 13.61% and 6.8%, respectively.     

A Hybrid Eukaryotic–Prokaryotic Nanoplatform with Photothermal Modality for Enhanced Antitumor Vaccination

Cytomembrane-derived nanoplatforms are an effective biomimetic strategy in cancer therapy. To improve their functionality and expandability for enhanced vaccination, a eukaryotic–prokaryotic vesicle (EPV) nanoplatform is designed and constructed by fusing melanoma cytomembrane vesicles (CMVs) and attenuated Salmonella outer membrane vesicles (OMVs). Inheriting the virtues of the parent components, the EPV integrates melanoma antigens with natural adjuvants for robust immunotherapy and can be readily functionalized with complementary therapeutics. In vivo prophylactic testing reveals that the EPV nanoformulation can be utilized as a prevention vaccine to stimulate the immune system and trigger the antitumor immune response, combating tumorigenesis. In the melanoma model, the poly(lactic-co-glycolic acid)–indocyanine green (ICG) moiety (PI)-implanted EPV (PI@EPV) in conjunction with localized photothermal therapy with durable immune inhibition shows synergetic antitumor effects as a therapeutic vaccine. The eukaryotic–prokaryotic fusion strategy provides new perspectives for the design of tumor-immunogenic, self-adjuvanting, and expandable vaccine platforms.