Erythrocyte Membrane-Enveloped Polymeric Nanoparticles as Nanovaccine for Induction of Antitumor Immunity against Melanoma

Abstract

Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen-specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp10025-33) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor-occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-γ secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy.

Vitamin E-Oligo(methyl diglycol l-glutamate) as a Biocompatible and Functional Surfactant for Facile Preparation of Active Tumor-Targeting PLGA Nanoparticles

“…28,29 It should be noted that the hydrophobic vitamin E head portion and hydrophilic oligopeptide tail are bulky and have large surface areas, which is an essential characteristic of a good surfactant. The terminal 4 amino groups of VEOEG surfactants following preparation of nanoparticles via nanoprecipitation would locate on the surface of PLGA NPs, and facilitate both shell-crosslinking and ligand decoration with biomolecules like polysaccharides, peptides, and antibodies, affording robust and multifunctional PLGA NPs for active tumor-targeting chemotherapy.…”

Curative effect of laparoscopic surgery on acute gastric perforation

“…C3b receptor (CR1) can identify and scavenge the circulating immune complex. Meanwhile, it can enhance the T lymphocyte function through surface molecules of CD58, CD59 and CR3 [30,31]. We can know by analyzing the indexes of immune response in erythrocyte, that the fluorescence intensities of CR3, CD58 and CD59 and the garland number of C3bR and ICR of red blood cells in peripheral blood from the LS group were all significantly higher than those of the laparotomy group, which indicated that patients with acute gastric perforation treated by laparoscopic surgery showed slighter inhibition effect on body immune function and more satisfactory postoperative recovery of immune function.…”

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

“…[23][24][25][26][27] According to the parameters, including density of polymeric cores, the mean particle sizes before and after the RBCm coating, mean surface area of …”

“…In consideration of enormous quantity in vivo as well as simple structure and properties, red blood-cell membrane (RBCm) was the earliest and most widely explored for building synthetic biomimetic nanocarriers. [23][24][25][26][27] RBCm coating containing membrane proteins (eg, CD47, 28 C8bp, 29 and HRP 30 ) can retain their original biological properties completely, 22 disguise NPs as RBCs, 31 evade the immune response from the mononuclear phagocyte system to prolong systemic circulation without the accelerated blood clearance phenomenon, 19 and concurrently reduce reticuloendothelial system uptake. 32 This provides more opportunity to accumulate at tumor sites.…”