Injection/infusion reactions to nanopharmaceuticals (and particulate drug carriers) are idiosyncratic and well documented. The molecular basis of nanoparticle-mediated injection reactions is debatable, with two hypotheses as front-runners. The first is complement-activation-related ‘pseudoallergy’, where a causal role for nanoparticle-mediated complement activation in injection/infusion reactions is considered. However, the second hypothesis (the rapid phagocytic response hypothesis) states a transitional link from robust clearance of nanoparticles (NPs) from the blood by strategically placed responsive macrophages to adverse hemodynamic and cardiopulmonary reactions, regardless of complement activation. Here, I critically examine and discuss these hypotheses. Current experimentally derived evidence appears to be more in support of the rapid phagocytic response hypothesis than of the ‘pseudoallergy’ hypothesis.

对纳米药物（和颗粒状药物载体）的注射/输注反应是特异的，并且有据可查。纳米粒子介导的注射反应的分子基础是有争议的，有两个假说是先行者。第一个是补体激活相关的“拟变态反应”，其中考虑了纳米颗粒介导的补体激活在注射/输注反应中的因果作用。然而，第二个假设（快速吞噬反应假设）指出，通过策略性放置响应性巨噬细胞，从纳米颗粒（NPs）从血液中的牢固清除到不良的血液动力学和心肺反应的过渡链接，无论补体激活如何。在这里，我批判性地研究和讨论这些假设。