Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo.
Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo.
复制标题
DOI：
10.1021/nn901297q
复制
发表时间：
2010-03-23
期刊：
影响因子：
17.1
通讯作者：
Adair JH
中科院分区：
文献类型：
--
作者：
Barth BM;Sharma R;Altinoğlu EI;Morgan TT;Shanmugavelandy SS;Kaiser JM;McGovern C;Matters GL;Smith JP;Kester M;Adair JH
癌症的早期诊断是成功治疗和长期有利患者的关键因素。死亡率高主要是由于诊断晚，因为症状可能直到疾病转移才出现，以及缺乏有效的系统治疗。晚期诊断通常与缺乏及时敏感的成像方式有关。纳米技术的前景目前受到无法同时寻找、治疗和成像癌性病变的限制。本研究描述了荧光磷硅酸钙纳米复合颗粒（CPNPs）的设计和合成，可以全身靶向乳腺癌和胰腺癌病变。CPNP是一种直径约20 nm的复合材料，由掺杂有硅酸盐的无定形磷酸钙基质组成，其中嵌入了近红外成像剂吲哚菁绿色（ICG）。在本研究中，我们描述和验证CPNP生物共轭的人全转铁蛋白，抗CD 71抗体，和短胃泌素肽通过抗生物素蛋白-生物素-或一种新的PEG-马来酰亚胺-偶联策略。生物素化的人全转铁蛋白（二铁转铁蛋白）和生物素化的抗CD 71抗体（抗转铁蛋白受体抗体）与抗生物素蛋白缀合的CPNP（抗生物素蛋白-CPNP）的缀合允许靶向在乳腺癌细胞上高度表达的转铁蛋白受体。类似地，通过PEG-马来酰亚胺偶联将生物素化的五肽胃泌素与抗生物素蛋白-CPNP偶联以及将十肽胃泌素（胃泌素-10）与PEG-CPNP偶联允许靶向在胰腺癌病变中过表达的胃泌素受体。这些生物缀合的CPNP具有作为治疗诊断模式的潜力，同时增强乳腺癌和胰腺癌肿瘤的药物递送、靶向和成像。
The early diagnosis of cancer is the critical element in successful treatment and long term favorable patient prognoses. The high rate of mortality is mainly attributed to the tendency for late diagnoses as symptoms may not occur until the disease has metastasized, as well as the lack of effective systemic therapies. Late diagnosis is often associated with the lack of timely sensitive imaging modalities. The promise of nanotechnology is presently limited by the inability to simultaneously seek, treat and image cancerous lesions. This study describes the design and synthesis of fluorescent calcium phosphosilicate nanocomposite particles (CPNPs) that can be systemically targeted to breast and pancreatic cancer lesions. The CPNPs are a ~20nm diameter composite composed of an amorphous calcium phosphate matrix doped with silicate in which a near infra-red imaging agent indocyanine green (ICG) is embedded. In the present studies, we describe and validate CPNP bioconjugation of human holotransferrin, anti-CD71 antibody, and short gastrin peptides via an avidin-biotin- or a novel PEG-maleimide-coupling strategy. The conjugation of biotinylated human holotransferrin (diferric transferrin) and biotinylated anti-CD71 antibody (anti-transferrin receptor antibody) to avidin conjugated CPNPs (Avidin-CPNPs) permits targeting of transferrin receptors, which are highly expressed on breast cancer cells. Similarly, the conjugation of biotinylated pentagastrin to Avidin-CPNPs and decagastrin (gastrin-10) to PEG-CPNPs via PEG-maleimide coupling permits targeting of gastrin receptors, which are over-expressed in pancreatic cancer lesions. These bioconjugated CPNPs have the potential to perform as a theranostic modality, simultaneously enhancing drug delivery, targeting and imaging of breast and pancreatic cancer tumors.
登录
查看更多内容
影响因子：
10.8
作者：
Kester M;Heakal Y;Fox T;Sharma A;Robertson GP;Morgan TT;Altinoğlu EI;Tabaković A;Parette MR;Rouse SM;Ruiz-Velasco V;Adair JH
通讯作者：
Adair JH
DOI：
10.1073/pnas.90.11.5076
发表时间：
1993-06-01
影响因子：
11.1
作者：
LIVNAH, O;BAYER, EA;SUSSMAN, JL
通讯作者：
SUSSMAN, JL
影响因子：
64.8
作者：
Grimm, Dirk;Streetz, Konrad L.;Kay, Mark A.
通讯作者：
Kay, Mark A.
DOI：
10.1152/ajpregu.1995.268.1.r135
发表时间：
1995-01-01
影响因子：
2.8
作者：
SMITH, JP;FANTASKEY, AP;ZAGON, IS
通讯作者：
ZAGON, IS
影响因子：
10.8
作者：
Muddana HS;Morgan TT;Adair JH;Butler PJ
通讯作者：
Butler PJ