Jaidev L R, Chellappan David Raj, Bhavsar Dhiraj Vasanth, Ranganathan Ravi, Sivanantham Banudevi, Subramanian Anuradha, Sharma Uma, Jagannathan Narnamangalam R, Krishnan Uma Maheswari, Sethuraman Swaminathan
Centre for Nanotechnology & Advanced Biomaterials, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
Central Animal House Facility, School of Chemical & Biotechnology, SASTRA University, Thanjavur 613401, India.
Acta Biomater. 2017 Feb;49:422-433. doi: 10.1016/j.actbio.2016.11.053. Epub 2016 Nov 23.
Theranostics has received considerable attention since both therapy and imaging modalities can be integrated into a single nanocarrier. In this study, fluorescent iron oxide (FIO) nanoparticles and gemcitabine (G) encapsulated poly(lactide-co-glycolide) (PLGA) nanospheres (PGFIO) conjugated with human epidermal growth factor receptor 2, (HER-2) antibody (HER-PGFIO) were prepared and characterized. HER-PGFIO showed the magnetic moment of 10emu/g, relaxivity (r) of 773mMs and specific absorption rate (SAR) of 183W/g. HER-PGFIO showed a sustained release of gemcitabine for 11days in PBS (pH 7.4). In vitro cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50% inhibitory concentration (IC) of 0.11mg/mL. Subcutaneous tumor xenografts of MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end of 30days showed significant tumor regression (86±3%) in the HER-PGFIO with magnetic hyperthermia (MHT) treatment group compared to control group. In vivo MRI imaging showed the enhanced contrast in HER-PGFIO+MHT treated group compared to control. HER-PGFIO showed significant tumor regression and enhanced MRI in treatment groups, which could be an effective nanocarrier system for the treatment of pancreatic cancer.
Combination therapies are best suitable to treat pancreatic cancer. Theranostics are the next generation therapeutics with both imaging and treatment agents encapsulated in a single nanocarrier. The novelty of the present work is the development of targeted nanocarrier that provides chemotherapy, thermotherapy and MRI imaging properties. The present work is the next step in developing the nanocarriers for pancreatic cancer treatment. Different treatment modalities embedding into a single nanocarrier is the biggest challenge that was achieved without compromising the functionality of each other. The surface modification of polymeric nanocarriers for antibody binding and their multifunctional abilities will appeal to wider audience.
由于治疗和成像方式可以整合到单个纳米载体中，治疗诊断学已受到广泛关注。在本研究中，制备并表征了与人类表皮生长因子受体2（HER-2）抗体（HER-PGFIO）偶联的荧光氧化铁（FIO）纳米颗粒和包裹吉西他滨（G）的聚（丙交酯-共-乙交酯）（PLGA）纳米球（PGFIO）。HER-PGFIO的磁矩为10emu/g，弛豫率（r）为773mMs，比吸收率（SAR）为183W/g。HER-PGFIO在PBS（pH 7.4）中显示吉西他滨持续释放11天。HER-PGFIO在3D MIAPaCa-2培养物中的体外细胞毒性评估显示，50%抑制浓度（IC）为0.11mg/mL。在SCID小鼠中建立了MIAPaCa-2皮下肿瘤异种移植模型，30天结束时的肿瘤消退研究表明，与对照组相比，接受磁热疗（MHT）治疗的HER-PGFIO组肿瘤显著消退（86±3%）。体内MRI成像显示，与对照组相比，HER-PGFIO+MHT治疗组的对比度增强。HER-PGFIO在治疗组中显示出显著的肿瘤消退和增强的MRI，这可能是一种治疗胰腺癌的有效纳米载体系统。
联合疗法最适合治疗胰腺癌。治疗诊断学是下一代治疗方法，将成像和治疗剂封装在单个纳米载体中。本研究的新颖之处在于开发了一种靶向纳米载体，它具有化疗、热疗和MRI成像特性。本研究是开发用于治疗胰腺癌的纳米载体的下一步。将不同的治疗方式嵌入单个纳米载体是最大的挑战，而本研究在不影响彼此功能的情况下实现了这一点。用于抗体结合的聚合物纳米载体的表面修饰及其多功能能力将吸引更广泛的关注。
