Introduction: Drug delivery systems based on natural particulates, as one of the most promising strategies, have potential for cancer therapy[1]. Taking advantages of biological functions and physical morphologies of natural particulates, these biomimetic drug carriers offer several significant advantages such as selective targeting, prolonged circulation time, and low immunogenicity[2,][3].
Materials and Methods: Here we describe a simple method to prepare an endosome membrane-coated nanogel (EM-NG) from source cancer cells[4]. Following intracellular uptake of methacrylated hyaluronic acid[5]-[7] (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating crosslinkers and photoiniators, EM-NG was easily formed through in situ polymerization initiated by UV irradiation inside endosome. The endosome containing HA nanogel is readily collected via the magnetic extraction with the help of the entrapped magnetic Fe3O4 nanocrystals. Then, a model anticancer drug Doxorubicin (DOX) was further loaded into EM-NG via dispersion.
Results and Discussion: The TEM image showed the EM-NGs were round-oval in shape (Figure 1A), and the average diameter was 262.3 nm. The successful coating of endosome membrane was validated by the western blotting analysis against the early endosome antigen 1. The resulting DOX loaded EM-NG (DOX-EM-NG) was demonstrated to efficiently target the source cancer cells through a specific homotypic affinity. Moreover, DOX-EM-NGs were able to moreefficiently deliver anticancer drug to source cancer cells than the nanogel without endosome membrane(Figure 1B), while there were insignificant differences compared to DOX-NGs when treated toward non-source cancer cells.
Figure 1. (A) The TEM image of EM-NG. (Scale bar: 200 nm) (B) In vitro cytotoxicity of EM-NG, free DOX, DOX-NG and DOX-EM-NG towards HeLa cells after incubation for 24 h. *P <0.05.
Conclusions: We developed a facile method to prepare endosome membrane-coated nanogels as biomimetic drug carrier. This endosome-mimicking nanogel showed excellent targeting ability to the homotypic cells. This study illustrates the potential of utilizing endosome membrane-mimicking formulation for targeted cancer therapy, and offers guideline for developing bio-inspired drug delivery system.
the grant from NC TraCS, NIH’s Clinical and Translational Science Awards (CTSA, NIH grant 1UL1TR001111) at UNC-CH
References:
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