Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.
Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts.
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在人转移性乳腺癌细胞加骨成骨细胞的共培养物中转移性三阴性乳腺癌细胞对抗体靶向的磷硅酸钙纳米颗粒的优先摄取。
DOI：
10.1016/j.nano.2021.102383
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Adair JH
中科院分区：
文献类型：
--
作者：
Bussard KM;Gigliotti CM;Adair BM;Snyder JM;Gigliotti NT;Loc WS;Wilczynski ZR;Liu ZK;Meisel K;Zemanek C;Mastro AM;Shupp AB;McGovern C;Matters GL;Adair JH
磷硅酸钙纳米粒子 (CPSNP) 是可生物吸收的纳米粒子，可以与靶向分子生物共轭并封装活性剂，并将其递送至肿瘤细胞，而不会对邻近的健康组织造成损害。这项研究中获得的数据表明，CPSNP 上的抗 CD71 抗体在体外将这些纳米颗粒靶向三阴性乳腺癌细胞，并增强其内化。 Caspase 3,7 激活、DNA 损伤和荧光显微镜证实了由吉西他滨单磷酸封装的靶向抗 CD71-CPSNP 引起的细胞凋亡乳腺癌反应，吉西他滨单磷酸是用于治疗乳腺癌和卵巢癌等癌症的化疗药物吉西他滨的活性代谢物。与成骨细胞共培养的乳腺癌细胞优先将荧光团罗丹明 WT 封装的靶向抗 CD71-CPSNP 内化。虽然成骨细胞部分内化抗 CD71-GemMP-CPSNP，但它们的细胞生长并未受到影响。这些结果表明，CPSNP 可用作已转移至骨的乳腺癌的成像工具和选择性药物递送系统。磷硅酸钙纳米粒子使用抗体直接靶向三阴性乳腺癌细胞并递送化疗药物吉西他滨。骨骼是乳腺癌转移的首选部位，一旦乳腺癌侵入骨骼，总体生存率和生活质量就会很差。目前还没有可选择性靶向骨转移性乳腺癌细胞同时保留内源性骨基质细胞的治疗方法。我们开发了一种有效的货物封装方法，利用磷酸硅酸钙纳米颗粒封装化疗药物吉西他滨单磷酸盐、近红外成像剂罗丹明 WT，并与 CD71 抗体生物缀合，以增强对乳腺癌细胞的选择性靶向。 A) αCD71-磷硅酸钙纳米颗粒靶向转移性乳腺癌细胞，随后在晚期内体中摄取和溶解纳米颗粒，并将显像剂和/或药物释放到细胞质中。 B) 磷酸钙纳米复合颗粒显示罗丹明 WT 和单磷酸吉西他滨共同封装在磷硅酸钙基质中，以及 1) 具有胺末端的甲氧基聚乙二醇用于被动靶向或 2) αCD71 的表面生物共轭，用于主动靶向乳腺癌细胞上的转铁蛋白受体。
Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents -and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs, targets these nanoparticles to and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone. Calcium phosphosilicate nanoparticles that directly target triple negative breast cancer cells using antibodies and deliver the chemotherapeutic gemcitabine. Bone is a preferred site of breast cancer metastases and once breast cancer invades the bone, overall survival and quality of living is poor. Currently there are no therapeutics available that selectively target the bone metastatic breast cancer cells while sparing endogenous bone stromal cells. We have developed an effective cargo encapsulation method utilizing calcium phosphosilicate nanoparticles encapsulated with the chemotherapeutic gemcitabine monophosphate, near-infrared imaging agent rhodamine WT, and bioconjugated with an antibody to CD71 to enhance selective targeting of breast cancer cells. A) αCD71-calcium phosphosilicate nanoparticles target metastatic breast cancer cells for subsequent uptake and dissolution of nanoparticles in late endosome and release of imaging agent and/or drug into the cytosol. B) Calcium phosphate nanocomposite particle showing co-encapsulation of rhodamine WT and gemcitabine monophosphate in a calcium phosphosilicate matrix, as well as surface bioconjugation of either 1) methoxy-polyethylene glycol with amine termination for passive targeting or 2) αCD71 for active targeting of transferrin receptors on breast cancer cells.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
影响因子：
17.1
作者：
Barth, Brian M.;Shanmugavelandy, Sriram S.;Kaiser, James M.;McGovern, Christopher;Altnoglu, Erhan I.;Haakenson, Jeremy K.;Hengst, Jeremy A.;Gilius, Evan L.;Knupp, Sarah A.;Fox, Todd E.;Smith, Jill P.;Ritty, Timothy M.;Adair, James H.;Kester, Mark
通讯作者：
Kester, Mark
影响因子：
3.8
作者：
Malorni L;Shetty PB;De Angelis C;Hilsenbeck S;Rimawi MF;Elledge R;Osborne CK;De Placido S;Arpino G
通讯作者：
Arpino G
影响因子：
3.3
作者：
Matuo, Renata;Sousa, Fabricio Garmus;Pegas Henriques, Joao Antonio
通讯作者：
Pegas Henriques, Joao Antonio
DOI：
10.1016/j.nano.2017.06.017
发表时间：
2017-10
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
作者：
Loc WS;Linton SS;Wilczynski ZR;Matters GL;McGovern CO;Abraham T;Fox T;Gigliotti CM;Tang X;Tabakovic A;Martin JA;Clawson GA;Smith JP;Butler PJ;Kester M;Adair JH
通讯作者：
Adair JH