Cell source determines the immunological impact of biomimetic nanoparticles

Abstract

Recently, engineering the surface of nanotherapeutics with biologics to provide them with superior biocompatibility and targeting towards pathological tissues has gained significant popularity. Although the functionalization of drug delivery vectors with cellular materials has been shown to provide synthetic particles with unique biological properties, these approaches may have undesirable immunological repercussions upon systemic administration. Herein, we comparatively analyzed unmodified multistage nanovectors and particles functionalized with murine and human leukocyte cellular membrane, dubbed Leukolike Vectors (LLV), and the immunological effects that may arise in vitro and in vivo. Previously, LLV demonstrated an avoidance of opsonization and phagocytosis, in addition to superior targeting of inflammation and prolonged circulation. In this work, we performed a comprehensive evaluation of the importance of the source of cellular membrane in increasing their systemic tolerance and minimizing an inflammatory response. Time-lapse microscopy revealed LLV developed using a cellular coating derived from a murine (i.e., syngeneic) source resulted in an active avoidance of uptake by macrophage cells. Additionally, LLV composed of a murine membrane were found to have decreased uptake in the liver with no significant effect on hepatic function. As biomimicry continues to develop, this work demonstrates the necessity to consider the source of biological material in the development of future drug delivery carriers.

Post-nano strategies for drug delivery: multistage porous silicon microvectors

“…Furthermore, in vivo results demonstrated that mMSVs exhibited delayed liver accumulation and increased circulation time compared to the hMSVs. 60 These results indicate that syngeneic membrane components are necessary for effective avoidance of the mononuclear phagocyte system, an effect that is most likely due to interspecies differences in self-tolerance proteins.…”

“…Syngeneic leukolike MSVs were prepared by coating particles with murine macrophage membranes (mMSV), while xenogeneic leukolike MSVs had a human T lymphocyte coating (hMSV). 60 Cell culture experiments revealed that although mMSVs and hMSVs both interacted with murine macrophages, only the former was able to avoid cellular internalization. Furthermore, in vivo results demonstrated that mMSVs exhibited delayed liver accumulation and increased circulation time compared to the hMSVs.…”

Strategies for the enhanced intracellular delivery of nanomaterials

“…Another strategy is to use biomimetic surfaces, whereby the nanomaterial surface is modified with a natural membrane coating to avoid phagocytic clearance, prolong drug circulation, and improve the biocompatibility. Markers, such as CD47 [66] or even leukocytes, are attached to the surface of the nanomaterial to camouflage it, in that the body recognizes it as 'self' [67].…”

Nanomedicine in Melanoma: Current Trends and Future Perspectives

“…As NPs are in the size range of biological aggressors, interactions with the immune system are more likely to occur. Thus, a major limitation in nanomedicine is the correct evaluation of the fate of the nanodrugs as antitumoral effectors within a biological system (140)(141)(142)(143)(144)(145)(146). As nanomaterials match the same size range as biomolecules and cellular structures endows them with the propensity to reach intracellular structures previously accessible only to biological aggressors.…”