Hybrid red blood cell membrane coated porous silicon nanoparticles functionalized with cancer antigen induce depletion of T cells

Abstract

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimicking block copolymer polydimethylsiloxane-b-poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4⁺ and cytotoxic CD8⁺ T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases.

Fig. 1. This study features two different types of hybrid nanoparticles. The first type has UnPSi encapsulated within RBC membrane. TRP2 peptides are anchored on the RBC membrane via a cell membrane-mimicking block copolymer PDMS-PMOXA. The second type has UnPSi, surface-functionalized with TRP2 peptides, which are encapsulated within RBC membranes.

Fig. 2. (a) TEM micrograph of Un-TRP2@RBC. Encapsulated UnPSi NP appear as a dark irregular object inside the light dark RBC membrane. (b) TEM micrograph of UnPSi@RBC-p-TRP2. (c) A secondary electron SEM micrograph showing UnPSi nanoparticle enveloped by a RBC membrane. (d) Backscattered electron SEM micrograph of UnPSi-TRP2@RBC. The rectangle inside a particle shows the area where the EDX spectrum in (e) was measured from. (e) EDX spectrum, which indicates elemental Si from the PSi NP and P from the RBC membrane.

Fig. 3. T cell depletion induced by the NP samples after 72 h co-incubation with 700 000 PBMCs. N = 3 for all experiments; *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.005.

Fig. 4. The percentage of apoptotic CD3⁺ T-cells in the T cell population. N = 3 for all experiments; *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.005.