Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo.
Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo.
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DOI：
10.1016/j.jconrel.2016.01.030
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发表时间：
2016-03-10
期刊：
影响因子：
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通讯作者：
Al-Jamal KT
中科院分区：
文献类型：
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作者：
Hassan HA;Smyth L;Rubio N;Ratnasothy K;Wang JT;Bansal SS;Summers HD;Diebold SS;Lombardi G;Al-Jamal KT
碳纳米管（CNT）在增强抗原向抗原呈递细胞的递送方面表现出显着的能力。然而，对于改变碳纳米管的物理性质如何影响抗原呈递细胞（例如树突状细胞（DC））对抗原的摄取尚未建立正确的理解。我们假设改变多壁碳纳米管（MWNT）-抗原缀合物的物理性质，例如长度和表面电荷，可以影响 DC 对 MWNT 抗原的内化，从而影响诱导的免疫反应效力。为此，将原始 MWNT (p-MWNT) 暴露于各种化学反应以改变其物理特性，然后与模型抗原卵清蛋白 (OVA) 结合。产生的 MWNT-OVA 缀合物是长 MWNT-OVA (~ 386 nm)，带有净正电荷 (5.8 mV)，或短 MWNT-OVA (~ 122 nm)，带有增加的负电荷 (− 23.4、− 35.8 或 − 39 mV)。与带有高负电荷的短MWNT-OVA相比，具有最低负电荷的短MWNT-OVA在体外和体内表现出更好的细胞摄取和OVA特异性免疫反应。然而，长的带正电荷的 MWNT-OVA 显示出有限的细胞摄取和 OVA 特异性免疫反应，而短的 MWNT-OVA 显示出最少的负电荷。我们认为，减少 MWNT-抗原缀合物的电荷负性可增强细胞摄取，从而增强引发的免疫反应强度。然而，MWNT-抗原缀合物的长度也可能影响细胞摄取和免疫反应效力；强调了物理特性作为设计基于 MWNT 的疫苗输送系统时考虑因素的重要性。
Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs)-antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT-OVA (~ 386 nm), bearing net positive charge (5.8 mV), or short MWNTs-OVA (~ 122 nm) of increasing negative charges (− 23.4, − 35.8 or − 39 mV). Compared to the short MWNTs-OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system.