Thermosensitive hydrogels based on polypeptides for localized and sustained delivery of anticancer drugs

Thermosensitive hydrogels based on poly(γ-ethyl-l-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-l-glutamate) triblock copolymers (PELG-PEG-PELG) were prepared for localized and sustained delivery of anticancer drugs. The polypeptide-based hydrogels showed much lower critical gelation concentration than the traditional polyester-based hydrogels. In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for ∼21 days, and H&E staining study suggested acceptable biocompatibility of our materials in vivo. Then the hydrogels were tried as injectable implants to encapsulate antitumor drug, paclitaxel (PTX), to assess the in situ anti-tumoral activity using liver cancer xenograft model. The results demonstrated that the PTX-incorporated hydrogels could efficiently suppress the tumor growth, and did not result in obvious damage to normal organs. Therefore, the polypeptide-based thermosensitive hydrogels designed in the present study have great potential to serve as an effective platform for localized anti-cancer drug delivery.     

Sharp pH-sensitive amphiphilic polypeptide macrophotosensitizer for near infrared imaging-guided photodynamic therapy

Tumor environmental sensitive polypeptide integrated photosensitizer is a platform for imaging-guided photodynamic therapy (PDT). However, the photosensitizer leakage during blood circulation, poor accumulation in tumor tissue and inferior quantum yield of singlet oxygen are still challenges. Herein, NHS-active boron-dipyrromethene derivative with bromine substituted NHS-BODIPY-Br₂ was first synthesized, which possessed high singlet oxygen generation efficiency and near infrared (NIR) fluorescence, and then it was conjugated to a sharp pH (6.36) sensitive polypeptide to achieve a macrophotosensitizer for NIR imaging-guided PDT. In vitro study showed that the macrophotosensitizer nanoparticles exhibited good cellular uptake and ability to kill cancer cells. Once accumulating in the tumor tissues, the nanoparticles can be demicellized by tumor acidity to promote cellular uptake, which could enlarge fluorescence signal intensity and enhance in vivo PDT therapeutic effect upon NIR laser irradiation. It provides a strategy to design photosensitizer conjugated tumor acidity sensitive polypeptide for NIR imaging-guided photodynamic therapy.     

Thermoresponsive release from poly(Glu(OMe))-block-poly(Sar) microcapsules with surface-grafting of poly(N-isopropylacrylamide)

Thermoresponsive microcapsules were prepared by grafting poly(N-isopropylacrylamide) (PNIPAAm) on the surface of polypeptide (poly(Glu(OMe))-block-poly(Sar)) microcapsules. Naked poly(Glu(OMe))-block-poly(Sar) microcapsules were partly hydrolysed with NaOH to remove methyl groups and newly formed carboxyl groups were used to anchor polyallylamine having 4,4′-azobis(4-cyanovaleric acid) groups. Graft polymerization of N-isopropylacrylamide at the microcapsule surface was initiated by photo-cleavage of the azo groups. Microscopic examination showed that a homogeneous dense skin layer of PNIPAAm was formed on the surface of microcapsule at 40°C, while the skin layer became loose when the temperature was lowered to 25°C. Dextran release from the microcapsule was faster below the lower critical solution temperature (LCST) of PNIPAAm than that above it. When the temperature changed across the LCST, a reversible, thermoresponsive release from the microcapsule was observed. Notably, the transition of the release rate by changing the temperature occurs quickly in a narrow temperature range.     

抗肺癌相关多肽的研究进展

肿瘤放疗和化疗过程中都存在较大的毒副作用,而肿瘤靶向性治疗既能降低毒副作用、减少用药量,又可提高药物的疗效。筛选与肿瘤特异性结合多肽已成为实现靶向治疗肿瘤的热点之一,并取得了一定的成果。肺癌目前的治疗方法主要是手术和放、化疗,虽然可以增加患者的存活率,但放、化疗毒副作用明显,耐受性差。现将与肺癌靶向性有关的多肽研究进展综述如下。     

氨基糖苷类及多肽类抗生素中硫酸盐的两种测定方法比较

的：比较并探讨氨基糖苷类及多肽类抗生素中硫酸盐的两种测定方法。方法：用络合滴定法和HPLC-ELSD法分别对三种抗生素中的硫酸盐进行测定；HPLC-ELSD法色谱柱为Grace Apollo C18（4.6 mm×250 mm，5 μm），流动相为0.2 mol﹒L-1三氟乙酸溶液-甲醇柱温35 ℃，进样量20 μl。结果：进行两种方法配对t检验分析，t=0.436，P＞0.05，结果无显著性差异。结论：络合滴定法为经典分析方法，成本低廉，但需要始终保持待测液pH值11，且调节pH时应注意避免反应离子及待测离子的损失，操作繁琐，耗时较长，在滴定过程中产生的白色沉淀对终点的判断有影响，主观性较强；而HPLC-ELSD法测定三种抗生素中的硫酸盐，专属性、准确度、精密度均良好 ,方法易操作，克服了滴定法判断终点的主观性，能更为准确快捷地测定氨基糖苷类及多肽类抗生素中硫酸盐的含量。