Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer.
Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer.
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DOI：
10.1039/c2ib20125a
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Dhar S
中科院分区：
文献类型：
--
作者：
Marrache S;Choi JH;Tundup S;Zaver D;Harn DA;Dhar S
将光动力疗法（PDT）的光毒性和免疫刺激能力与免疫系统的广泛有效性相结合的治疗技术可以非常有希望治疗转移性乳腺癌。我们推测，现有的多组分疗法的分子机制的知识可以提供线索，以帮助使用纳米颗粒（NP）递送平台发现免疫刺激剂与光敏剂（PS）的新组合。当施用治疗组合时的治疗挑战包括选择剂量以减少副作用、确定递送正确的药物比例以及暴露于感兴趣的靶标。这些因素在单独给药时很难实现。通过结合基于控释聚合物的NP药物递送方法，我们能够将基于锌酞菁（ZnPc）的PS与CpG-ODN（一种已知的免疫刺激剂，其以时间调节的方式管理远处肿瘤，从而更有效地管理致命的转移性乳腺癌）一起差异性地递送至转移性乳腺癌细胞。我们封装ZnPc，这是一个长波长吸收PS内的聚合物NP核心由聚（D，L-乳酸-共-乙醇酸）-b-聚（乙二醇）（PLGA-b-PEG）。在用金纳米颗粒（AuNP）涂覆聚合物核的外部之后，我们用CpG-ODN进一步修饰AuNP表面。使用4 T1转移性小鼠乳腺癌细胞的体外细胞毒性显示，在用660 nm激光照射后，含有ZnPc和CpG-ODN两者的杂合NP具有显著的光细胞毒性，并且该活性显著优于单独的任一种处理。用PDT杀死的4 T1细胞裂解物处理小鼠骨髓来源的树突状细胞表明，PDT与协同免疫刺激剂在单一NP系统中的组合导致显著的免疫应答，其可用于治疗转移性癌症。
A therapeutic technology that combines the phototoxic and immune-stimulating ability of photodynamic therapy (PDT) with the widespread effectiveness of the immune system can be very promising to treat metastatic breast cancer. We speculated that the knowledge of molecular mechanisms of existing multi-component therapies could provide clues to aid the discovery of new combinations of an immunostimulant with a photosensitizer (PS) using a nanoparticle (NP) delivery platform. Therapeutic challenges when administering therapeutic combinations include the choice of dosages to reduce side effects, the definitive delivery of the correct drug ratio, and exposure to the targets of interest. These factors are very difficult to achieve when drugs are individually administered. By combining controlled release polymer-based NP drug delivery approaches, we were able to differentially deliver zinc phthalocyanine (ZnPc) based PS to metastatic breast cancer cells along with CpG-ODN, a single-stranded DNA that is a known immunostimulant to manage the distant tumors in a temporally regulated manner resulting in more effective management of deadly metastatic breast cancer. We encapsulated ZnPc which is a long-wavelength absorbing PS within a polymeric NP core made up of poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG). After coating the outside of the polymeric core with gold NPs (AuNPs), we further modified the AuNP surface with CpG-ODN. In vitro cytotoxicity using 4T1 metastatic mouse breast carcinoma cells shows significant photocytotoxicity of the hybrid NPs containing both ZnPc and CpG-ODN after irradiation with a 660 nm LASER light and this activity was remarkably better than either treatment alone. Treatment of mouse bone marrow derived dendritic cells with the PDT-killed 4T1 cell lysate shows that the combination of PDT with a synergistic immunostimulant in a single NP system results in significant immune response, which can be used for the treatment of metastatic cancer.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
DOI：
10.1089/oli.1.1996.6.133
发表时间：
1996-06-01
期刊：
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
影响因子：
--
作者：
Krieg, AM;Matson, S;Fisher, E
通讯作者：
Fisher, E
DOI：
10.1073/pnas.96.16.9305
发表时间：
1999-08-03
影响因子：
11.1
作者：
Hartmann, G;Weiner, GJ;Krieg, AM
通讯作者：
Krieg, AM
影响因子：
4.4
作者：
Gollnick SO;Brackett CM
通讯作者：
Brackett CM
DOI：
10.1039/c0pp00326c
发表时间：
2011-05
期刊：
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
影响因子：
--
作者：
St Denis TG;Aziz K;Waheed AA;Huang YY;Sharma SK;Mroz P;Hamblin MR
通讯作者：
Hamblin MR